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Docetaxel anhydrous side effects: Docetaxel (Intravenous Route) Side Effects

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Docetaxel (Intravenous Route) Side Effects

Side Effects

Drug information provided by: IBM Micromedex

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur:

More common

  1. Black, tarry stools

  2. bleeding gums

  3. blistering, peeling, or loosening of the skin

  4. blood in the urine or stools

  5. burning, tingling, numbness, or pain in the hands, arms, feet, or legs

  6. chest pain

  7. chills

  8. cough

  9. decrease in the amount of urine

  10. diarrhea

  11. difficulty in swallowing

  12. difficulty moving

  13. dizziness

  14. dry eyes

  15. fainting

  16. fast, slow, or irregular heartbeat

  17. fever

  18. heartburn

  19. hives, itching, skin rash

  20. hoarseness

  21. irritation

  22. joint pain, stiffness, or swelling

  23. lower back or side pain

  24. muscle pain, cramps, or stiffness

  25. noisy, rattling breathing

  26. nosebleeds

  27. pain or burning feeling in the throat

  28. painful or difficult urination

  29. pale skin

  30. pinpoint red spots on the skin

  31. red skin lesions, often with a purple center

  32. red, irritated eyes

  33. redness of the skin

  34. sensation of pins and needles

  35. severe lack or loss of strength

  36. sore throat

  37. sores, ulcers, or white spots on the lips or tongue or inside the mouth

  38. stabbing pain

  39. swelling of the eyelids, face, lips, hands, or feet

  40. tightness in the chest

  41. trouble breathing

  42. troubled breathing at rest

  43. troubled breathing with exertion

  44. unusual bleeding or bruising

  45. unusual tiredness or weakness

  46. vomiting

  47. weight gain
Less common

  1. Bluish color of the skin

  2. blurred vision

  3. burning or itching of the eyes

  4. changes in skin color

  5. chest discomfort

  6. confusion

  7. constipation

  8. discharge, excessive tearing

  9. dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

  10. lightheadedness

  11. nausea

  12. pain or discomfort in the arms, jaw, back, or neck

  13. pain, tenderness, or swelling of the foot or leg

  14. rapid, shallow breathing

  15. redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid

  16. severe stomach pain

  17. sweating

  18. vomiting of blood or material that looks like coffee grounds
Rare

  1. Dilated neck veins

  2. extreme tiredness or weakness

  3. fast, pounding, or irregular heartbeat or pulse

  4. headache

  5. irregular breathing

  6. nervousness

  7. pounding in the ears
Incidence not known

  1. Agitation

  2. dark urine

  3. decreased awareness or responsiveness

  4. depression

  5. drowsiness

  6. dry mouth

  7. general feeling of tiredness or weakness

  8. hostility

  9. increased thirst

  10. indigestion

  11. light-colored stools

  12. loss of appetite

  13. loss of consciousness

  14. mood or mental changes

  15. muscle spasms (tetany) or twitching seizures

  16. nausea

  17. rapid, shallow breathing

  18. rectal bleeding

  19. seizures

  20. severe abdominal pain, cramping, or burning

  21. severe sleepiness

  22. stomach cramps, pain, or tenderness

  23. stomach pain, continuing

  24. tremor

  25. unusual drowsiness, dullness, or feeling of sluggishness

  26. vomiting of material that looks like coffee grounds, severe and continuing

  27. yellow eyes or skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

  1. Absent, missed, or irregular menstrual periods

  2. bad, unusual or unpleasant (after)taste

  3. change in sense of smell

  4. change in taste

  5. discoloration of the fingernails or toenails

  6. dry skin hair loss or thinning of hair

  7. stopping of menstrual bleeding

  8. swelling or inflammation of the mouth

  9. weight loss
Less common

  1. Dry, red, hot, or irritated skin
Incidence not known

  1. Hearing loss

  2. pain and redness of the skin at the place of earlier radiation treatment

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Portions of this document last updated: April 01, 2021

Copyright © 2021 IBM Watson Health. All rights reserved. Information is for End User’s use only and may not be sold, redistributed or otherwise used for commercial purposes.


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Docetaxel – Drug Information – Chemocare


Chemocare.com

Care During Chemotherapy and Beyond



(doe-se-TAKS-sel)


Trade name: Taxotere®


Chemocare.com uses generic drug names in all descriptions of drugs. Taxotere is
the trade name for docetaxel. In some cases, health care professionals may use the
trade name taxotere when referring to the generic drug name docetaxel.


Drug type:   Docetaxel is an anti-cancer (“antineoplastic”
or “cytotoxic”) chemotherapy drug.  This medication is classified as a “plant
alkaloid,” a “taxane” and an “antimicrotubule agent.”  (For more detail, see
“How this drug works” section below).

What Docetaxel Is Used For:

  • Approved in treatment of breast cancer, non-small cell lung cancer, advanced stomach
    cancer, head and neck cancer and metastatic prostate cancer.
  • Also being investigated to treat small cell lung, ovarian, bladder, and pancreatic
    cancers, soft tissue sarcoma and melanoma.


Note:  If a drug has been approved for one use, physicians
may elect to use this same drug for other problems if they believe it may be helpful.

How Docetaxel Is Given:

  • Docetaxel is given through a vein (intravenously, IV)  
  • There is no pill form of docetaxel
  • Premedication with a corticosteroid pill starting a day prior to docetaxel infusion
    for 3 days is given to reduce the severity of fluid retention and allergic reactions. 
    Your doctor will prescribe the exact regimen.
  • The amount of docetaxel that you will receive depends on many factors, including
    your height and weight, your general health or other health problems, and the type
    of cancer or condition being treated.  Your doctor will determine your dose
    and schedule.

Side Effects:


Important things to remember about the side effects of docetaxel:

  • Most people do not experience all of the side effects listed
  • Side effects are often predictable in terms of their onset and duration
  • Side effects are almost always reversible and will go away after treatment is complete
  • There are many options to help minimize or prevent side effects
  • There is no relationship between the presence or severity of side effects and the
    effectiveness of the medication.
  • The side effects of docetaxel and their severity depend on how much of the drug
    is given.  In other words, high doses may produce more severe side effects).


The following side effects are common (occurring in greater than 30%) for
patients taking docetaxel:

  • Low white blood cell count.  (This can increase your risk for infection)
  • Low red blood cell count (anemia)



Nadir: Meaning low point, nadir is the point in time between chemotherapy
cycles in which you experience low blood counts.



Onset: 4-7 days
Nadir: 5-9 days
Recovery: 21 days


  • Fluid retention with weight gain, swelling of the ankles or abdominal area.


  • Peripheral neuropathy (numbness in your fingers and toes) may occur with repeated
    doses. This should be reported to your healthcare provider.

  • Nausea
  • Diarrhea
  • Mouth sores
  • Hair loss
  • Fatigue and weakness
  • Infection
  • Nail changes (Color changes to your fingernails or toenails may occur while taking
    docetaxel. In extreme, but rare, cases nails may fall off. After you have finished
    docetaxel treatments, your nails will generally grow back) (see skin problems).


These side effects are less common, meaning they occur in 10-29 percent
of patients receiving docetaxel:

  • Vomiting
  • Muscle/bone/joint pain (myalgias and arthralgias)
  • Low platelet count (This can increase your risk of bleeding)
  • Increases in blood tests measuring liver function.  These return to normal
    once treatment is discontinued. (see liver problems)


Infusion-related side effects (symptoms which may occur during the actual
treatment) include:

  • Allergic reactions (rash, flushing, fever, lowered blood pressure).  Happens
    rarely, usually occurs in the first or second infusion.  Frequency is reduced
    by premedication with corticosteroid starting one day before infusion.  You
    will be monitored closely during the infusion for any signs of allergic reaction.
  • Infusion site reactions (uncommon and generally mild, consist of darkening of the
    vein, inflammation, redness or dryness of the skin, or swelling of the vein).


Not all side effects are listed above, some that are rare (occurring in less than
10% of patients) are not listed here.  However, you should always inform your
health care provider if you experience any unusual symptoms.

When to contact your doctor or health care provider:


Contact your health care provider immediately, day or night, if you
should experience any of the following symptoms:

  • Fever of 100.4° F (38° C) or higher, chills (possible signs of infection)


The following symptoms require medical attention, but are not an emergency. 
Contact your health care provider within 24 hours of noticing any of the
following:

  • Nausea (interferes with ability to eat and unrelieved with prescribed medication).
  • Vomiting (vomiting more than 4-5 times in a 24 hour period).
  • Diarrhea (4-6 episodes in a 24-hour period).
  • Unusual bleeding or bruising.
  • Black or tarry stools, or blood in your stools or urine.
  • Extreme fatigue (unable to carry on self-care activities).
  • Mouth sores (painful redness, swelling or ulcers).
  • Yellowing of the skin or eyes.
  • Swelling of the ankles.  Weight gain.  Swelling of the stomach. 
  • Shortness of breath.


Always inform your health care provider if you experience any unusual symptoms.

Precautions:

  • Before starting docetaxel treatment, make sure you tell your doctor about any other
    medications you are taking (including prescription, over-the-counter, vitamins,
    herbal remedies, etc.).   Do not take aspirin, products containing aspirin
    unless your doctor specifically permits this.
  • Do not receive any kind of immunization or vaccination without your doctor’s approval
    while taking docetaxel.
  • Inform your health care professional if you are pregnant or may be pregnant prior
    to starting this treatment. Pregnancy category D (docetaxel may be hazardous to
    the fetus.  Women who are pregnant or become pregnant must be advised of the
    potential hazard to the fetus).
  • For both men and women: Do not conceive a child (get pregnant) while taking docetaxel. 
    Barrier methods of contraception, such as condoms, are recommended. Discuss with
    your doctor when you may safely become pregnant or conceive a child after therapy.
  • Do not breast feed while taking this medication.

Self-Care Tips:

  • You may be at risk of infection so try to avoid crowds or people with colds or not
    feeling well, and report fever or any other signs of infection immediately to your
    health care provider.
  • Wash your hands often.
  • To help treat/prevent mouth sores, use a soft toothbrush, and rinse three times
    a day with 1/2 to 1 teaspoon of baking soda and/or 1/2 to 1 teaspoon of salt mixed
    with 8 ounces of water.
  • Use an electric razor and a soft toothbrush to minimize bleeding.
  • Avoid contact sports or activities that could cause injury.
  • To reduce nausea, take anti-nausea medications as prescribed by your doctor, and
    eat small, frequent meals.  
  • Avoid sun exposure.  Wear SPF 15 (or higher) sunblock and protective clothing.
    Drink at least two to three quarts of fluid every 24 hours, unless you are instructed
    otherwise.
  • In general, drinking alcoholic beverages should be kept to a minimum or avoided
    completely.  You should discuss this with your doctor.
  • Get plenty of rest. 
  • Maintain good nutrition.
  • If you experience symptoms or side effects, be sure to discuss them with your health
    care team. They can prescribe medications and/or offer other suggestions that
    are effective in managing such problems.

Monitoring and Testing:


You will be checked regularly by your health care professional while you are taking
docetaxel, to monitor side effects and check your response to therapy.  Periodic
blood work to monitor your complete blood count (CBC) as well as the function of
other organs (such as your kidneys and liver) will also be ordered by your doctor.    

How Docetaxel Works:


Cancerous tumors are characterized by cell division, which is no longer controlled
as it is in normal tissue. “Normal” cells stop dividing when they come into contact
with like cells, a mechanism known as contact inhibition.  Cancerous cells
lose this ability.  Cancer cells no longer have the normal checks and balances
in place that control and limit cell division.  The process of cell division,
whether normal or cancerous cells, is through the cell cycle.  The cell cycle
goes from the resting phase, through active growing phases, and then to mitosis
(division).


The ability of chemotherapy to kill cancer cells depends on its ability to halt
cell division.  Usually, the drugs work by damaging the RNA or DNA that tells
the cell how to copy itself in division.  If the cells are unable to divide,
they die.  The faster the cells are dividing, the more likely it is that chemotherapy
will kill the cells, causing the tumor to shrink.  They also induce cell suicide
(self-death or apoptosis).


Chemotherapy drugs that affect cells only when they are dividing are called cell-cycle
specific.  Chemotherapy drugs that affect cells when they are at rest are called
cell-cycle non-specific.  The scheduling of chemotherapy is set based on the
type of cells, rate at which they divide, and the time at which a given drug is
likely to be effective.  This is why chemotherapy is typically given in cycles.


Chemotherapy is most effective at killing cells that are rapidly dividing. 
Unfortunately, chemotherapy does not know the difference between the cancerous cells
and the normal cells. The “normal” cells will grow back and be healthy but in the
meantime, side effects occur.  The “normal” cells most commonly affected by
chemotherapy are the blood cells, the cells in the mouth, stomach and bowel, and
the hair follicles; resulting in low blood counts, mouth sores, nausea, diarrhea,
and/or hair loss.  Different drugs may affect different parts of the body.


Docetaxel belongs to a class of chemotherapy drugs called plant alkaloids. Plant
alkaloids are made from plants.  The vinca alkaloids are made from the periwinkle
plant (catharanthus rosea). The taxanes are made from the bark of the Pacific Yew
tree (taxus).  The vinca alkaloids and taxanes are also known as antimicrotubule
agents. The podophyllotoxins are derived from the May apple plant. Camptothecan
analogs are derived from the Asian “Happy Tree” (Camptotheca acuminata).  Podophyllotoxins
and camptothecan analogs are also known as topoisomerase inhibitors.  The plant
alkaloids are cell-cycle specific.  This means they attack the cells during
various phases of division.

  • Vinca alkaloids: Vincristine, Vinblastine and Vinorelbine
  • Taxanes:  Paclitaxel and Docetaxel
  • Podophyllotoxins:  Etoposide and Tenisopide
  • Camptothecan analogs: Irinotecan and Topotecan


Antimicrotubule agents (such as docetaxel), inhibit the microtubule structures within
the cell.  Microtubules are part of the cell’s apparatus for dividing and replicating
itself.  Inhibition of these structures ultimately results in cell death.


Note:  We strongly encourage you to talk with your health
care professional about your specific medical condition and treatments. The information
contained in this website is meant to be helpful and educational, but is not a substitute
for medical advice.

Chemocare.com is designed to provide the latest information about chemotherapy to patients and their families, caregivers and friends. For information about the 4th Angel Mentoring Program visit www.4thangel.org

Information on Minor & Severe Reactions

Taxotere, also known as docetaxel, is a chemotherapy drug that doctors prescribe to treat several different cancers — most commonly, breast cancer. While the drug is effective at treating breast cancer, it is associated with several side effects, ranging from common skin reactions to very rare instances of leukemia.

Because Taxotere is a strong chemotherapy drug, its side effects tend to be more extreme than drugs that treat less serious issues such as high cholesterol or blood pressure. Doctors may lower the dose or prescribe drugs that reduce the risk of allergic reactions to deal with these types of side effects.


Common reported side effects of Taxotere (docetaxel) include:

  • Injection site pain or swelling

  • Temporary hair loss

  • Nausea

  • Vomiting

  • Diarrhea

  • Constipation

  • Loss of appetite

  • Fingernail or toenail changes

In addition, the drug carries a black box warning that includes five complications that can be severe or fatal: toxic death, low blood cell counts, liver toxicity, fluid retention and hypersensitivity reactions.

From 2003 to June 2018, people reported to the FDA Adverse Events Reporting System (FAERS) a total of 21,037 adverse events related to the medication. Of those reports, 17,346 were serious and 3,007 resulted in deaths.

Some studies also link the drug to permanent hair loss on the scalp and the rest of the body, including eyebrows and eyelashes. While not a life-threatening side effect, the hair loss is distressing to women who may survive their breast cancer diagnosis but will have to learn to cope without hair.

The hair often does not grow back even months to years after treatment has ended. Permanent hair loss is the subject of nearly 10,000 federal lawsuits against Taxotere’s maker, Sanofi.

Acute Side Effects

Some issues with Taxotere can occur during treatment or shortly after. Doctors check liver, kidney and bone marrow function to make sure a patient can tolerate the chemotherapy drug and that any acute reactions can be treated.

Most of these complications go away between treatments or after the medication is stopped, according to a 2014 article by Maria Y. Ho and John R. Mackey published in Cancer Management and Research.

Infusion Reactions

Taxotere frequently triggers infusion reactions, according to Ho and Mackey. These typically occur within minutes or hours of receiving the chemotherapy drug.

Doctors administer antihistamines and glucocorticoids before the infusion to minimize these reactions. Still, about 2 percent of patients may experience potentially life-threatening reactions.

Researchers think docetaxel plus the solvent in the infusion, polysorbate 80, may contribute to allergic reactions.


Infusion reactions include:

  • Flushing

  • Itching

  • Shortness of breath

  • Fever

  • Hypersensitivity reactions such as angioedema, skin problems, wheezing, difficulty breathing and cardiorespiratory arrest

Low White Blood Cell Counts

Low white blood cell counts, also called neutropenia, can occur in people who take Taxotere. A more serious version accompanied with fever is called febrile neutropenia. Sometimes, it can be serious enough to cause an infection that requires hospitalization.

Neutropenia is a common side effect of most chemotherapy drugs. Usually white blood cell counts drop around 10 days to 14 days after patients first get chemotherapy. But, compared to other breast cancer therapy agents, docetaxel has a higher risk of febrile neutropenia, according to Ho and Mackey.

Results From Clinical Studies

About 12 percent of patients who had received 100 mg/m2 of Taxotere during clinical studies experienced febrile neutropenia.

The effects can become worse depending on the combination of drugs given with docetaxel. For example, the risk of febrile neutropenia is 5 percent to 25 percent with doxorubicin/cyclophosphamide followed by docetaxel, and it goes up to 21 percent to 24 percent with adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide), according to Ho and Mackey.

In initial clinical studies, mild neutropenia occurred in all patients on doses of 60 mg/m2 to 100 mg/m2, according to the medication insert. Doctors typically reduce the dose in patients with declining cell counts.

Fluid Retention

Fluid retention is one of the side effects mentioned in Taxotere’s black box warning. It is one of the more frequent side effects of the drug, according to Ho and Mackey.

The medication causes fluid buildup in the limbs and around the heart and lungs. Most of the time, the side effect is mild to moderate.

Doctors typically try to give patients corticosteroids to prevent swelling, but fluid retention can still occur in some patients after premedication. According to the medication insert, about six out of 92 patients experienced severe fluid retention even after premedication. These patients had to have the fluid drained.

The condition is sometimes slow to reverse. It took about 16 weeks from the last infusion to completely resolve in some patients.

Fact

Premedication reduced fluid retention with Taxotere by about 18 percent.

Skin and Nail Reactions

Skin reactions, including redness and swelling of the arms and legs with peeling of the skin, can occur with Taxotere, according to the medication label. Patients with abnormal liver function are at increased risk of severe skin toxicity.

Symptoms usually start with tingling in the palm and soles, followed by tenderness, swelling and blistering. In some cases, skin reactions occur just at the IV site.

Docetaxel users have reported severely itchy rashes on the feet, hands, arms, face and chest. The reported reactions were generally not disabling and happened within a week after an infusion. Patients recovered before their next treatments.

In clinical trials, 15 out of 965 women stopped using Taxotere because of skin problems. According to the medication insert, women who had taken corticosteroids before their infusions did not suffer severe skin rashes.

But, some independent studies reported cases of serious skin problems in people who had been premedicated. For example, Ming J. Poi and colleagues wrote that they observed 34 patients treated with docetaxel, and five of them suffered severe skin toxicity reactions within three days after treatment.

All but one patient had received corticosteroid, antihistamine and histamine-2 (h3) receptor blocker before docetaxel.

NAIL PROBLEMS

Nail toxicities usually resolve six to 12 months after patients stop chemotherapy.

In addition to skin problems, docetaxel can cause separation of the nail from the nail bed, splintering, abnormal thickening and nail infections. Using frozen gloves and socks can reduce blood flow to the affected areas. This may help delay symptoms from starting and may make them less severe if they do occur.

Pneumonitis and Gastrointestinal Complications

Researchers have received rare reports of lung disease that occurred during, within a few hours of or several weeks after treatment, Ho and Mackey reported. Patients may experience difficulty breathing, fever, dry cough and tiredness.

People with pre-existing lung disease are at higher risk, and the risk goes up with higher dosages of docetaxel. Most cases resolve after patients stop taking the drug.

Some women may also suffer gastrointestinal complications from colitis after receiving docetaxel. This can cause gastrointestinal perforation and dehydration.

Signs of serious complications include severe diarrhea and abdominal pain. Some patients may need surgery for perforations.

Symptoms of Alcohol Intoxication

In June 2014, the U.S. Food and Drug Administration warned that docetaxel contains alcohol, which can cause patients to feel drunk after treatment. The agency revised the drug’s label to include warnings about the risk.

Docetaxel manufacturers use alcohol, also known as ethanol, to dissolve the active ingredients so the drug can be given intravenously. Different brand-name products contain varying amounts of alcohol.

Patients should not drive or operate machinery for one to two hours after their infusions. Pain relievers, sleep aids and other medications may interact with the alcohol in the infusion and make the intoxicating effects worse.

Did You Know

Each administration of Taxotere Injection at 100 mg/m2 delivers 2.0 g/m2 of alcohol.

Tell your doctor about all the medicines you are currently taking and if you have problems with alcohol or other conditions that may be affected by ethanol in docetaxel.

The FDA advises doctors and nurses to monitor patients for signs of being drunk during and after treatment. Let your doctor know if you experience symptoms of being drunk, confusion, stumbling or becoming very sleepy during or after an infusion. Lowering the infusion rate may help resolve the symptoms.

Lawsuit Information

Taxotere lawsuits filed by more than 10,000 breast cancer survivors and their families say manufacturers hid the risk of permanent hair loss caused by the drug.

View Lawsuits

Long-Term Side Effects

Many side effects of Taxotere are acute and treatable. Doctors either manage them with premedication, or the reactions resolve on their own after treatment is stopped. But the drug can cause a few long-term side effects.

The most common long-term side effects of docetaxel are two types of nerve damage called sensory and motor peripheral neuropathy. Although it is less common, patients have also reported hair loss that lasts for years and appears to be permanent. In extremely rare cases, patients have developed leukemia.

Neuropathy

A study published in the February 2015 issue of European Journal of Cancer found 15 percent of breast cancer survivors treated with docetaxel reported peripheral neuropathy within one to three years after treatment “with significant negative impact” on health-related quality of life.

Major symptoms include numbness and tingling in the hands and feet and loss of reflexes. These side effects are much less common with docetaxel than another drug in the same class, paclitaxel. In a 2017 study by Summer Karafiath and colleagues, three out of 21 women developed docetaxel-induced neuropathy versus 15 out of 21 women in the paclitaxel group.

Studies show less than 10 percent of people who took docetaxel suffered the most serious symptoms, and the severity increased with the dose. Moderate neuropathy symptoms occurred at a dosage of 371 mg/m2, according to phase III trial results from a study by Steve Jones and colleagues and reported by Ho and Mackey.

So far, doctors have not found an adequate solution to treat this type of neuropathy. But they typically watch for these symptoms during treatments and reduce the dose or delay therapy if the side effect presents. Some doctors may prescribe an anticonvulsive drug called gabapentin to help reduce symptoms.

Hair Loss

Alopecia, or hair loss, is a common side effect of chemotherapy. Typically, hair grows back within three to six months after discontinuation of treatment. But some women who took Taxotere reported permanent hair loss. The rare side effect can have a negative impact on survivors’ quality of life.

“It put a lot of strain on my marriage,” said Ami Dodson, a breast cancer survivor living with chemo-induced alopecia. “It still is rough. It has had a traumatic toll on my relationship with my husband, my self-image, my self-esteem, and it has been hard on my kids, too.”

In a breast cancer trial, 687 out of 744 women treated with a combination of Taxotere plus doxorubicin and cyclophosphamide (TAC) suffered alopecia, according to the drug’s medication insert. At the end of the median follow-up period of eight years, nearly 4 percent of those women still had not regrown their hair.

Independent studies in clinical practice found higher numbers. For example, study results presented by Nicola Thorp and colleagues at the National Cancer Research Institute Cancer Conference in 2014 found 10 percent to 15 percent of patients suffered “long term significant” hair loss.

“Long term hair loss has a significant impact on quality of survival,” the authors wrote. “This risk should be discussed routinely (as part of the process of informed consent) with all patients embarking upon docetaxel as a component of management of [early breast cancer].”

Acute Myeloid Leukemia (AML)

The risk is extremely low; however, people who receive Taxotere in combination with certain other medications can develop a type of blood cancer called acute myeloid leukemia, or AML. The disorder occurs more often in patients who are treated with the drugs and radiation therapy.

Three out of 744 clinical trial participants who received Taxotere, doxorubicin and cyclophosphamide (TAC) developed the blood cancer. One patient died.

Patients may experience changes in blood counts due to leukemia and other blood disorders years after treatment. Those who receive TAC need to be monitored for delayed myelodysplasia or myeloid leukemia.

Docetaxel (Taxotere) | Breast Cancer Now

1. What is docetaxel?
2. When is docetaxel given?
3. Before starting docetaxel?
4. How is docetaxel given?
5. Side effects of docetaxel
6. Allergic reaction
7. Blood clots
8. Sex, contraception and pregnancy
9. Travel and vaccinations
10. Further support

1. What is docetaxel?

Docetaxel is a chemotherapy drug. Chemotherapy is a treatment that destroys cancer cells using anti-cancer drugs. Docetaxel is the non-branded name of the drug, but you may hear it called by one of its brand names such as Taxotere.

2. When is docetaxel given?

Primary breast cancer

Docetaxel is used to treat primary breast cancer (cancer that has not spread beyond the breast or the lymph nodes under the arm) in combination with other chemotherapy drugs. 

Before surgery 

Docetaxel can be given before surgery to shrink a larger breast cancer. This may mean breast-conserving surgery is an option, rather than a mastectomy. Or it might be given before surgery to slow down the growth of a fast-growing breast cancer and reduce the chance of it spreading to other parts of the body. 

When chemotherapy is given before surgery it’s called primary or neo-adjuvant chemotherapy.

After surgery 

Docetaxel is given after surgery to reduce the risk of breast cancer coming back in the future. It usually starts within a few weeks of your operation. If you are going to have radiotherapy you will usually complete your course of docetaxel first. 

When chemotherapy is given after surgery it is called adjuvant therapy. 

Breast cancer that has spread

Docetaxel is used alone or with other chemotherapy or anti-cancer drugs to treat breast cancer that has: 

  • Spread to the tissues and lymph nodes around the chest, neck and under the breastbone (known as regional recurrence or locally advanced breast cancer)
  • Spread to other parts of the body (secondary breast cancer)

3. Before starting docetaxel

Before starting your treatment most hospitals will arrange a chemotherapy information session. At this appointment a nurse will discuss how and when you will have your chemotherapy and how side effects can be managed. 

You may have blood tests and some people may have an ECG (electrocardiogram), a simple test that checks your heart rhythm. Your height and weight will also be measured, this is needed to work out the correct dose of chemotherapy for you.

You’ll be given contact numbers so you know who to phone if you have any questions or concerns.

4. How is docetaxel given?

Docetaxel is given into a vein (intravenously). This will usually be as a drip, also called an infusion, into the hand or arm.

Other intravenous methods may be used depending on factors such as how easy it is for chemotherapy staff to find suitable veins, and your preferences. 

Read about the different ways chemotherapy can be given.

Docetaxel is normally given once every three weeks, over about one hour. This is known as a cycle.

The interval between each treatment gives your body time to recover. This may vary depending on whether the number of blood cells has returned to normal between each cycle.

You will have docetaxel as an outpatient.

Before each cycle you will be given medication to reduce the chances of any possible reactions. 

How long will I have docetaxel for?

For primary breast cancer three to six treatment cycles are usually given. 

For locally advanced and secondary breast cancer the number of cycles will vary depending on the individual.

5. Side effects of docetaxel

Like any treatment, docetaxel can cause side effects. Everyone reacts differently to drugs and some people have more side effects than others. These side effects can usually be managed and those described here will not affect everyone.

If you are concerned about any side effects, regardless of whether they are listed here, talk to your chemotherapy nurse or cancer specialist (oncologist) as soon as possible.

If you are being given other chemotherapy or anti-cancer drugs with docetaxel, you may have additional side effects from these drugs.

Common side effects 

Effects on the blood

Docetaxel can temporarily affect the number of healthy blood cells in the body. You will have regular blood tests throughout your treatment to check your blood count. If the number of blood cells is too low, your next course of treatment may be delayed or the dose of the chemotherapy reduced.

Risk of infection

When the white blood cells fall below a certain level, it’s known as neutropenia. Not having enough white blood cells can increase the risk of getting an infection. Your resistance to infection is usually at its lowest point around 7–14 days after the docetaxel has been given. The number of white blood cells usually returns to normal before your next course of chemotherapy is due.

Your treatment team may give you guidelines to follow for reporting signs of an infection, but generally you should contact your hospital immediately if you experience any of the following:

  • You have a high temperature (over 37.5°C) or low temperature (under 36°C), or whatever your chemotherapy team has advised
  • You suddenly feel unwell, even with a normal temperature
  • You have any symptoms of an infection, for example a sore throat, a cough, a need to pass urine frequently or feeling cold and shivery

Before starting chemotherapy your treatment team should give you a 24-hour contact number or tell you where to get emergency care. 

You may need antibiotics. 

Your doctor might recommend injections of drugs called growth factors. This helps the body produce more white blood cells to reduce your risk of infection. 

Anaemia

Having too few red blood cells is called anaemia. If you feel particularly tired, breathless or dizzy, let your treatment team know. 

Bruising and bleeding

You may bruise more easily, have nosebleeds or your gums may bleed when you brush your teeth. Tell your treatment team if you experience any of these symptoms.

Hair loss 

Docetaxel causes hair loss. Most people will lose all their hair, including eyebrows, eyelashes and body hair.

You may begin to lose your hair about two weeks after the first treatment, but it can happen earlier. Hair loss is usually gradual but it can happen very quickly, possibly over a couple of days. 

Scalp cooling may stop you losing some, or all, of the hair on your head. 

Any hair loss should be temporary and in most cases your hair will begin to grow back a few weeks after your treatment has ended.

There’s some evidence that docetaxel treatment may result in prolonged or permanent hair loss. Permanent hair loss is described as incomplete regrowth of hair six months or more after completing treatment. There’s currently no definite evidence to say how often this happens.

If you’re concerned about hair loss when making decisions about treatment, talk to your oncologist and breast care nurse.

Read more about hair loss, scalp cooling and looking after your hair.

Numbness and tingling in hands or feet

People having docetaxel may have pain, numbness or tingling in their hands and feet. This is due to the effect of docetaxel on the nerves and is known as peripheral neuropathy. 

If you have tingling or numbness (such as difficulty doing up buttons, or difficulty feeling the difference between hot and cold water with your fingertips), mention this to your treatment team so they can monitor your symptoms. 

Painful muscles and joints

Your muscles or joints may ache or become painful two to three days after you have your treatment. This usually wears off after a few days to a week but may last a bit longer for some people. It can be very painful and you may need to take pain relief or anti-inflammatory drugs such as ibuprofen. It’s a good idea to have some of these available before starting your treatment just in case you need them. Be aware that pain relief such as paracetamol or ibuprofen can mask the signs of infection.

Before using anti-inflammatory pain relief, ask your doctor about the correct dose, how long you should use it for and any possible side effects, especially if you have a stomach ulcer or asthma.

Nausea and vomiting

Nausea (feeling sick) is usually mild and most people will not actually vomit (be sick). 

You may start to feel unwell a few hours after your treatment. You’ll be given anti-sickness medication, as tablets or into a vein, before each cycle of chemotherapy. You’ll also have some anti-sickness tablets to take home.

If nausea and vomiting are affecting you, let someone in your treatment team know.

Contact your hospital if you have severe vomiting and cannot drink any fluids without vomiting, even if it happens at the weekend or during the night.

Fluid retention 

You may develop a build-up of fluid in the body (oedema), which can take a few weeks to go away. This can appear as swollen ankles and legs and feeling short of breath. 
You’ll be given steroid drugs to prevent an allergic reaction to docetaxel, which will also help reduce the chance of fluid building up. 

Skin reactions

You may develop a rash anywhere on your body or your skin might discolour. This could be red and itchy or you may feel flushed. Your doctor might prescribe medicine to help. 
If you have skin reactions, mention this to your treatment team when you see them next so they can monitor your symptoms.

Some people have a skin reaction called hand-foot syndrome, often called Palmar-Plantar syndrome. It usually affects the palms of the hands and soles of the feet, but you may also have symptoms in other areas such as the skin on the knees or elbows.

Nail reactions

Docetaxel may cause changes to the appearance of your nails on your fingers and toes. This can be a change in the nail colour or texture, such as ridges forming. Nails can become more brittle and cracked. Occasionally the nail may lift off the nail bed and fall out, but nails will grow back.

As you’re more at risk of infection while having chemotherapy, report any signs of infection such as redness, heat, swelling or pain in or under your fingernails and toenails to your treatment team.

Sore mouth

Your mouth may become sore and small ulcers can develop. You’ll usually be given mouthwash to reduce the risk of a sore mouth developing. If you do get a mouth infection your specialist or chemotherapy nurse can advise you about different mouthwashes or suitable medicine. 

It’s advisable to see your dentist for a check-up before chemotherapy begins, and to avoid dental treatment during chemotherapy if possible. 

Taste changes

While you are having docetaxel, your sense of taste can change and some foods may taste different, such as more salty, bitter or metallic. You may no longer enjoy some of the foods you used to. If this is the case speak to your treatment team – they may be able to suggest ways of managing this. Your taste should return to normal once your treatment has finished.

Find out more about diet and dealing with changes to your taste and appetite during treatment.

Diarrhoea or constipation 

You may have diarrhoea or constipation. Your chemotherapy team can prescribe medicine to help control it and can give you information about diet. 

Contact your chemotherapy team if you have four or more episodes of diarrhoea within 24 hours.

Fatigue (extreme tiredness)

You may become extremely tired during your treatment. For some people, this fatigue can last for several weeks or even months after the treatment has finished. There are some things that can help improve fatigue – your treatment team may be able to help you with this. 

Find out more about fatigue.

Effects on your concentration 

Some people find treatment affects their ability to concentrate and makes them more forgetful. This is sometimes referred to as ‘chemo brain’ or ‘chemo fog’, but your treatment team may call it cognitive impairment. It usually improves over time after treatment has finished.

Pain in the injection site

Pain can occur where the needle has been inserted or anywhere along the vein. Tell your chemotherapy nurse immediately if you have pain, stinging or a burning sensation around the cannula (small plastic tube) while the drug is being given. 

If docetaxel leaks out of the vein it is being given in (called extravasation), it can damage the surrounding tissue.  

After treatment, you may have pain where the needle was inserted, or along the vein. After a few weeks you may notice tenderness, darkening and hardening around where the needle was inserted. This should fade in time.

Effects on fertility

It’s not known exactly what effect docetaxel has on fertility. However, any effects will also depend on other chemotherapy drugs you are having at the same time or have had in the past, and your age. 

If you’re concerned about your fertility, talk to your treatment team before treatment begins.

Find out more about how breast cancer treatment can affect fertility.

Less common side effects

Changes in heart rate and blood pressure

Docetaxel can alter your heart rate and affect blood pressure so you will be carefully monitored for this during your treatment. Changes to your heart rate and blood pressure can usually be treated easily and you will not have to stop your treatment. This is not the same as having an allergic reaction to docetaxel (see below).

Effects on the lungs

This may include scarring or inflammation of the lung tissue. This is a rare side effect, but if you become breathless or develop a dry cough during or in the few weeks after your treatment, let your treatment team know.

6. Allergic reaction

Before your treatment starts you will be given drugs called steroids to reduce the risk of an allergic reaction. These are usually given as tablets to take for three days starting the day before each cycle of chemotherapy. Take these as directed by your treatment team and do not stop taking them without talking to the team first.

If you have an allergic reaction to docetaxel, it will probably happen within the first few minutes of your treatment. It’s most likely the first or second time you have the drug. Reactions can vary from mild to severe, although severe reactions are uncommon.

You’ll be monitored closely during your treatment so that any reaction can be dealt with immediately. 

Symptoms of an allergic reaction include:

  • Flushing
  • Skin rash
  • Itching
  • Back pain
  • Shortness of breath
  • Faintness
  • Fever or chills 

If you have a severe reaction, treatment will be stopped immediately and you may not be given docetaxel again.

7. Blood clots

People with breast cancer have a higher risk of blood clots. Their risk is higher because of the cancer itself and some treatments for breast cancer. If the cancer has spread to other parts of the body (secondary breast cancer), this also increases the risk.

Having docetaxel increases the risk of blood clots such as deep vein thrombosis (DVT). People with a DVT are at risk of developing a pulmonary embolism (PE). This is when part of the blood clot breaks away and travels to the lung.

Blood clots can be harmful but are treatable so report symptoms as soon as possible.

If you experience any of the following symptoms contact your local A&E department, GP or treatment team straight away:

  • Pain, redness/discolouration, heat and swelling of the calf or thigh
  • Swelling, redness or tenderness where a central line is inserted to give chemotherapy, for example in the arm, chest area or up into the neck
  • Shortness of breath
  • Pain or tightness in the chest
  • Unexplained cough or coughing up blood

Find out more about blood clots.

8. Sex, contraception and pregnancy

You’re advised not to become pregnant while having treatment because docetaxel can harm a developing baby. If you haven’t been through the menopause, talk to your team about the most suitable method of contraception for you. It’s still possible to become pregnant even if your periods become irregular or stop. 

You can still have sex during treatment. It’s thought that chemotherapy drugs cannot pass into vaginal fluids or semen, but this cannot be completely ruled out as chemotherapy drugs can pass into the blood and some other body fluids. Most hospital specialists will advise using barrier methods of contraception, such as condoms, during treatment, and for a few days after chemotherapy is given.

Find out more about how breast cancer and its treatment can affect sex and intimacy and read our tips on how to manage these changes.

9. Travel and vaccinations

If you’re planning a holiday or need to travel overseas, check with your treatment team first.

You should not have any live vaccines while you are having chemotherapy. Live vaccines include mumps, measles, rubella (German measles), polio, BCG (tuberculosis), shingles and yellow fever.

Live vaccines contain a small amount of live virus or bacteria. If you have a weakened immune system, which you may do during chemotherapy, they could be harmful.

It is safe to have these vaccines six months after your chemotherapy finishes. Talk to your GP or treatment team before having any vaccinations.

If someone you have close contact with needs to have a live vaccine speak to your treatment team or GP. They can advise what precautions you may need to take depending on the vaccination.

Flu vaccination

Anyone at risk of a weakened immune system, and therefore more prone to infection, should have the flu vaccine. This includes people due to have or already having chemotherapy. The flu vaccine is not a live vaccine so does not contain any active viruses. Talk to your chemotherapy specialist or breast care nurse about the best time to have your flu jab.

10. Further support

Your chemotherapy team and breast care nurse can help with any questions you have. You can also call us free on 0808 800 6000 for information and support.
On our online Forum, you can find people going through treatment at the same time as you on the monthly chemotherapy threads.
 

 

Docetaxel (Taxotere) | Cancer information

Docetaxel is a type of chemotherapy. It is a treatment for a number of different types of cancer.

How it works

Chemotherapy works by destroying quickly dividing cells, such as cancer cells.

How you have docetaxel

You have docetaxel as a drip into your bloodstream (intravenously).

Drugs into your bloodstream

You might have the treatment through a drip into your arm. Your nurse puts a small tube (a cannula) into one of your veins and connects the drip to it.

Or you might need a central line. This is a long plastic tube that gives the drugs into a large vein, either in your chest or through a vein in your arm. It stays in the whole time you are having treatment.

When you have docetaxel

Each treatment takes about an hour and you have it once every 3 weeks.

Preventing allergic reactions

Docetaxel can cause an allergic reaction. To try to prevent this, your doctor or nurse give you steroid tablets to take. You usually take them for 3 days, starting the day before each treatment.

You can take steroids just a few hours before your treatment if you have prostate cancer. Your doctor can tell you how often you should take the steroids.

Tests

You have blood tests before and during your treatment. They check your levels of blood cells and other substances in the blood. They also check how well your liver and kidneys are working.

Side effects

We haven’t listed all the side effects. It’s very unlikely that you will have all of these side effects, but you might have some of them at the same time.

How often and how severe the side effects are can vary from person to person. They also depend on what other treatments you’re having. For example, your side effects could be worse if you’re also having other drugs or radiotherapy.

When to contact your team

Your doctor, nurse or pharmacist will go through the possible side effects. They will monitor you closely during treatment and check how you are at your appointments. Contact your advice line as soon as possible if:

  • you have severe side effects 
  • your side effects aren’t getting any better
  • your side effects are getting worse

Early treatment can help manage side effects better. 

Contact your doctor or nurse immediately if you have signs of infection, including a temperature above 37.5C or below 36C.

Common side effects

These side effects happen in more than 10 in 100 people (10%). You might have one or more of them. They include:

Risk of infection

Increased risk of getting an infection is due to a drop in white blood cells. Symptoms include a change in temperature, aching muscles, headaches, feeling cold and shivery and generally unwell. You might have other symptoms depending on where the infection is.

Infections can sometimes be life threatening. You should contact your advice line urgently if you think you have an infection. 

Breathlessness and looking pale

You might be breathless and look pale due to a drop in red blood cells. This is called anaemia.

You may have shortness of breath for other reasons. Tell your doctor if you feel short of breath.

Bruising, bleeding or nosebleeds

This is due to a drop in the number of platelets in your blood. These blood cells help the blood to clot when we cut ourselves. You may have nosebleeds or bleeding gums after brushing your teeth. Or you may have lots of tiny red spots or bruises on your arms or legs (known as petechiae).

Call your advice line if you have any signs of bleeding. Call 999 if you are bleeding a lot.

Allergic reaction

A reaction may happen during the infusion, causing a skin rash, itching, swelling of the lips, face or throat, breathing difficulties, fever and chills. Your nurse will give you medicines beforehand to try to prevent a reaction. Tell your nurse or doctor immediately if at any time you feel unwell. They will slow or stop your drip for a while and give you medicine to help relieve your symptoms.

Loss of appetite

You might lose your appetite for various reasons when you are having cancer treatment. Sickness, taste changes or tiredness can put you off food and drinks.

Hair loss

You could lose all your hair. This includes your eyelashes, eyebrows, underarm, leg and sometimes pubic hair. Your hair will usually grow back once treatment has finished but it is likely to be softer. It may grow back a different colour or be curlier than before. 

Feeling or being sick

Feeling or being sick is usually well controlled with anti sickness medicines. Avoiding fatty or fried foods, eating small meals and snacks, drinking plenty of water, and relaxation techniques can all help.

It is important to take anti sickness medicines as prescribed even if you don’t feel sick. It is easier to prevent sickness rather than treating it once it has started.

Diarrhoea

Contact your advice line if you have diarrhoea, such as if you’ve had 4 or more loose watery poos (stools) in 24 hours. Or if you can’t drink to replace the lost fluid. Or if it carries on for more than 3 days.

Your doctor may give you anti diarrhoea medicine to take home with you after treatment. Eat less fibre, avoid raw fruits, fruit juice, cereals and vegetables, and drink plenty to replace the fluid lost.

Mouth sores and ulcers

Mouth sores and ulcers can be painful. Keep your mouth and teeth clean; drink plenty of fluids; avoid acidic foods such as oranges, lemons and grapefruits; chew gum to keep the mouth moist and tell your doctor or nurse if you have ulcers.

Numbness or tingling in fingers or toes (peripheral neuropathy)

Numbness or tingling in fingers or toes is often temporary and can improve after you finish treatment. Tell your doctor if you’re finding it difficult to walk or complete fiddly tasks such as doing up buttons. 

Nail changes

During treatment your nails may change colour. This gradually goes after treatment as your nails grow. 

Your nail might separate from the nail bed and look white or yellow. The nail may eventually fall off but usually grows back.

Soreness, redness, peeling on palms or soles of the feet (hand foot syndrome) 

The skin on your hands and feet may become sore, red, or may peel. You may also have tingling, numbness, pain and dryness. This is called hand-foot syndrome or palmar plantar syndrome.

Moisturise your skin regularly. Your doctor or nurse will tell you what moisturiser to use.

You may also get a rash on your arms, face or chest.

Muscle pain

You might have muscle pain during treatment. Let your treatment team know so they can advise you on how to reduce it.

You may get pain in other areas of the body, such as the bones and less commonly your joints.

Lack of energy and strength

This is usually mild. You can do things to help yourself, including some gentle exercise. It’s important not to push yourself too hard and eat a well balanced diet.

Talk to your doctor or nurse if this effect is stopping you from doing your usual daily activities.

Fluid build up

A build up of fluid may cause swelling in your arms, hands, ankles, legs, face and other parts of the body. Contact your doctor if this happens to you.

Taste changes

Taste changes may make you go off certain foods and drinks. You may also find that some foods taste different from usual or that you prefer to eat spicier foods. Your taste gradually goes back to normal a few weeks after your treatment finishes.

Occasional side effects

These side effects happen in between 1 and 10 out of every 100 people (1 to 10%). You might have one or more of them. They include:

  • constipation – drink plenty and eat more fresh fruit and vegetables. Your nurse can give you laxatives to help if needed
  • tummy (abdominal pain) – tell your doctor or nurse if you have any pain or tenderness
  • changes to your blood pressure – tell your nurse if you feel dizzy, faint, or if you have headaches, nosebleeds, blurred or double vision, or shortness of breath
  • pain, swelling or redness around the site of the infusion – tell your nurse straight away if have any of these signs
  • changes to your liver – these don’t usually cause symptoms but are picked up on blood tests. These usually go back to normal after treatment has finished
  • irregular heart rhythm – you have tests to check for any changes

Rare side effects

These side effects happen in fewer than 1 in 100 people (1%). You might have one or more of them. They include:

  • heart failure
  • inflammation of the food pipe (oesophagus) – symptoms include heartburn and pain when swallowing

Coping with side effects

We have more information about side effects and tips on how to cope with them.

What else do I need to know?

Other medicines, foods and drink

Cancer drugs can interact with some other medicines and herbal products. Tell your doctor or pharmacist about any medicines you are taking. This includes vitamins, herbal supplements and over the counter remedies.

Docetaxel contains alcohol. Discuss with your doctor if there is any reason you shouldn’t take this. It may affect your ability to drive or use machines.

Loss of fertility

You may not be able to become pregnant or father a child after treatment with this drug. Talk to your doctor before starting treatment if you think you may want to have a baby in the future.

Men might be able to store sperm before starting treatment. And women might be able to store eggs or ovarian tissue. But these services are not available in every hospital, so you would need to ask your doctor about this.    

Contraception and pregnancy

This drug may harm a baby developing in the womb. It is important not to become pregnant or father a child while you are having treatment. 

Women must use reliable contraception during treatment. Men must use reliable contraception during treatment and for at least 6 months afterwards. Talk to your doctor or nurse about effective contraception before starting treatment.

Breastfeeding

Don’t breastfeed during this treatment because the drug may come through into your breast milk.

Treatment for other conditions

Always tell other doctors, nurses, pharmacists or dentists that you’re having this treatment if you need treatment for anything else, including teeth problems.

Immunisations

Don’t have immunisations with live vaccines while you’re having treatment and for up to 12 months afterwards. The length of time depends on the treatment you are having. Ask your doctor or pharmacist how long you should avoid live vaccinations.

In the UK, live vaccines include rubella, mumps, measles, BCG, yellow fever and the shingles vaccine (Zostavax).

You can:

  • have other vaccines, but they might not give you as much protection as usual
  • have the flu vaccine (as an injection)

Contact with others who have had immunisations – You can be in contact with other people who have had live vaccines as injections. Avoid close contact with people who have recently had live vaccines taken by mouth (oral vaccines) such as the oral typhoid vaccine.

If your immune system is severely weakened, you should avoid contact with children who have had the flu vaccine as a nasal spray. This is for 2 weeks following their vaccination.

Babies have the live rotavirus vaccine. The virus is in the baby’s poo for about 2 weeks and could make you ill if your immunity is low. Get someone else to change their nappies during this time if you can. If this isn’t possible, wash your hands well after changing their nappy.

More information about this treatment

We haven’t listed all the very rare side effects of this treatment. For further information see the electronic Medicines Compendium (eMC) website.

You can report any side effect you have that isn’t listed here to the Medicines Health and Regulatory Authority (MHRA) as part of their Yellow Card Scheme.

Presentation and management of docetaxel-related adverse effects in patients with breast cancer

Cancer Manag Res. 2014; 6: 253–259.

Maria Y Ho

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada

John R Mackey

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada

Division of Medical Oncology, Cross Cancer Institute, Edmonton, AB, Canada

Copyright © 2014 Ho and Mackey. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) LicenseThe full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.This article has been cited by other articles in PMC.

Abstract

The taxane chemotherapeutic agent docetaxel has been utilized in the management of breast cancer in the adjuvant, neoadjuvant and metastatic setting. Although well tolerated by the majority of patients, docetaxel toxicity may limit the dose which can be administered. Adverse events include infusion reactions, febrile neutropenia, fatigue, fluid retention, pneumonitis, cutaneous and nail toxicity, epiphora and lacrimal duct stenosis, gastrointestinal complications, and neuropathies. In this review, we explore these complications and how they can be effectively managed to improve patient quality of life during and following docetaxel therapy.

Keywords: toxicity, chemotherapy, adverse events

Introduction

Docetaxel (Taxotere®; Sanofi-Aventis Inc., Laval, QC, Canada) is an important antimicrotubule agent used to treat a variety of solid tumors including breast cancer, where docetaxel-containing regimens improve outcomes for patients in the metastatic, adjuvant, and neoadjuvant settings. This paper will provide an overview of the current roles of docetaxel in the treatment of metastatic and early-stage breast cancer as well as management of common side effects in cancer patients.

Efficacy of docetaxel and benefit to risk assessment in breast cancer

The use of adjuvant systemic chemotherapy has contributed greatly to the reduction in cause-specific mortality due to breast cancer in the Western Hemisphere.1 The decision to use adjuvant chemotherapeutic agents (ie, the administration of cytotoxic treatment following primary surgery) is largely driven by the anticipated risk of breast cancer distant recurrence, as determined by histology of invasive disease, expression of estrogen and/or progesterone receptors, human epidermal growth factor receptor (HER)-2 status, tumor size, nodal status, and age of the patient.2,3 In general, adjuvant chemotherapy is considered for patients with hormone-negative breast cancer with tumor size >0.5 cm or with pathological node involvement. For those patients with hormone receptor-positive breast cancer, chemotherapeutic agents are usually administered in the setting of pathologically positive lymph nodes, large tumor size, high tumor grade, and the presence of lymphovascular invasion and/or high recurrence score on gene expression recurrence assays.4

The taxanes, docetaxel and paclitaxel, are among the most effective single agents in early breast cancer. Clinically meaningful benefits of taxane incorporation in the adjuvant setting were affirmed in the Early Breast Cancer Trialists Collaborative Group 2012 meta-analysis for women with newly diagnosed breast cancer. The addition of taxane to anthracycline resulted in a further reduction in the event rate ratio of recurrence of 0.87, breast cancer mortality of 0.99, and overall mortality of 0.89 when compared with anthracycline alone.5 The benefits of taxane incorporation were independent of age, nodal status, tumor size, tumor grade, and hormone receptor status across clinical trials. As a result, anthracycline- and taxane-based chemotherapeutic regimens have become the standard of care in early stage breast cancers. Among the most active adjuvant chemotherapy regimens, the docetaxel-based combinations of docetaxel, doxorubicin, and cyclophosphamide (TAC),68 docetaxel with cyclophosphamide,9,10 sequential anthracycline (eg, FEC [5-fluorouracil, epirubicin, and cyclophosphamide]) followed by docetaxel monotherapy,1114 and docetaxel, carboplatin, and trastuzumab15 are most commonly used.

Similarly, combinations and sequences of anthracycline and taxanes have become the standard of care for preoperative neoadjuvant breast cancer chemotherapy. The value of docetaxel in the preoperative setting was first demonstrated with the Aberdeen study, in which tumor responses and overall survival were improved with sequential anthracycline–docetaxel when compared with continuing anthracycline chemotherapy.16,17

Taxanes also play an important role in the treatment of metastatic breast cancer. The aims of systemic treatment are to palliate symptoms, prolong survival, and maintain quality of life. Even though no prospective randomized controlled clinical trials have shown that systemic chemotherapy improves overall survival versus best supportive care, docetaxel-based trials have demonstrated improved survival outcomes in the setting of metastatic disease when compared with other chemotherapy regimens.1820 The outcomes for patients with metastatic breast cancer have improved significantly over the last two decades, and this is largely attributed to the availability of novel systemic therapies. A large retrospective study published by the British Columbia Agency Breast Tumor Group revealed that patients who were diagnosed with metastatic breast cancer between 1997 and 2001 had a 45% overall survival rate at 2 years in comparison with those who were diagnosed between 1991 and 1995 with only a 34% survival rate at 2 years.21 Chemotherapy is often the treatment choice for patients with visceral metastases associated with end-organ dysfunction, short disease-free interval, and those with rapidly progressive symptomatic disease given the higher likelihood of achieving a response rate.22

Docetaxel has comparable activity to anthracycline in the treatment of metastatic breast cancer.23 Taxanes are often the treatment of choice either as single agents or in combination in patients who are at risk for cardiac complications due to prior anthracycline exposure and those who developed metastases less than 12 months after prior anthracycline-based adjuvant therapy. Even though combinations of anthracycline and taxane generate high response rates, they are associated with a higher toxicity rate, with no clear survival advantage over sequential monotherapy.19,24 Consequently, combination regimens are generally reserved for patients with rapidly progressive and/or symptomatic visceral disease. Sequential single-agent chemotherapy is the treatment of choice for most patients with metastatic breast cancer due to a reasonable chance of response, successful symptom palliation, and improved quality of life while minimizing toxicities. For the subgroup of patients with hormone-positive disease, endocrine therapy is often used as the initial treatment of choice for those with soft tissue and bone metastases, while chemotherapy is reserved for those with visceral metastases.22

For those patients with HER-2-positive metastatic breast cancer, docetaxel has been shown to be synergistic with trastuzumab (the HER-2-directed monoclonal antibody) in preclinical models.25 Docetaxel is commonly combined with trastuzumab, where it has demonstrated important survival advantages in combination26,27 and, most recently, with the triplet therapy of docetaxel, trastuzumab, and pertuzumab (a monoclonal antibody that prevents HER family dimerization).28

Dosing schedules

Docetaxel has been used in breast cancer therapy in two dosing schedules which differ in toxicity profiles. The original registration regimen, and the most frequent in clinical practice, is intravenous administration at 3-weekly intervals, with a starting dose of between 60 and 100 mg/m2. Weekly intravenous docetaxel schedules are most commonly given day 1, day 8, and day 15 every 28-day cycle, with dosing of 25–35 mg/m2. The use of weekly docetaxel schedules is largely restricted to palliation of metastatic disease, where it has been shown to have fewer neutropenic complications than 21-day docetaxel but has somewhat lower anticancer activity and higher rates of skin toxicity and fatigue.14,29,30

Presentation of side effects and management of docetaxel-related adverse events

Docetaxel causes a variety of acute and long-term side effects. Fortunately, most of the common treatment-related toxicities, such as infusion reactions, febrile neutropenia, fatigue, and fluid retention are resolved between cycles of treatment or reversible upon treatment discontinuation. Prior to therapy administration, patients are screened for adequate renal function, hepatic function, and bone marrow function to ensure these acute side-effects are resolved. However, peripheral neuropathy is a long-term side effect of taxane chemotherapy that may be debilitating for patients well after completion of treatment.

Acute side effects

Infusion reactions

Docetaxel is one of the cytotoxic agents that frequently triggers acute infusion reactions. These reactions typically occur within minutes or hours of drug administration, with characteristic symptoms including “standard” reactions of flushing, itching, dyspnea, fever, hypoxia, and fever, and “classical hypersensitivity” reactions (ie, angioedema, urticaria, wheezing, stridor, anaphylaxis, and cardiorespiratory arrest).31 Hypersensitivity reactions tend to be most severe on rechallenge with the drug. Premedication with glucocorticoids and antihistamines prior to infusion can help to reduce and prevent the severity of reactions, and they are routinely administered to patients prior to docetaxel exposure. Even with premedication, approximately 2% of patients will experience potentially life-threatening reactions.32,33 While both the taxane and the solvent in which the drug is dissolved (polysorbate 80) can contribute to infusion reactions, the underlying mechanisms of docetaxel-induced infusion reactions still remain unclear.3438 Symptoms associated with standard infusion reactions and hypersensitivity/allergic reactions have been attributed mainly to cytokine release and mast cell/basophil activation, respectively. Initial management of standard infusion reactions includes temporary cessation of drug infusion for 30 minutes, with administration of additional intravenous antihistamines and glucocorticoids. Upon resolution of symptoms, infusion may be restarted at a slower rate. For anaphylaxis, stabilization of the cardiorespiratory system and use of epinephrine are indication, and discontinuation of drug infusion is usually required.

Febrile neutropenia

Myelosuppression is one of the most common treatment-related toxicities following administration of cytotoxic chemotherapy. Patients receiving combination chemotherapy experience a small to moderate reduction in their white cell count most commonly 10–14 days after initial administration. Febrile neutropenia is defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours with an absolute neutrophil count <0.5 × 109/L.39 The condition is associated with significant morbidity and mortality if not managed appropriately. Patients who develop febrile neutropenia are at increased risk of serious infections and often require hospitalization.

In contrast to many chemotherapeutic regimens used in breast cancer therapy, there is a high risk of developing febrile neutropenia with the various docetaxel-containing chemotherapeutic regimens. The cumulative risk of febrile neutropenia ranges from 5%–25% with doxorubicin/cyclophosphamide followed by docetaxel to 21%–24% with adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy when these regimens are given without primary prophylaxis with granulocyte colony stimulating factor (G-CSF). The consensus guidelines from the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) recommend the use of G-CSFs as primary prophylaxis if the risk of toxicity is estimated to be 20% or more, with the hope of reducing the incidence of neutropenic fever, duration of neutropenia, infectious complications, and rate of hospitalization.4043 Furthermore, secondary prophylaxis is warranted in patients who have developed febrile neutropenia with previous cycles of chemotherapy, particularly in the curative intent setting of (neo)adjuvant therapy where dose reduction may compromise outcome. In the metastatic setting, dose reduction is often instituted after development of febrile neutropenia to minimize future complications.

Treatment of febrile neutropenia typically involves risk assessment, blood cultures, admission into hospital and administration of broad-spectrum intravenous antibiotics, and close clinical monitoring. Even though the use of G-CSFs has been shown to shorten the duration of neutropenia, fever, and length of hospital stay, no survival benefit has been demonstrated. As a result, ESMO (European Society for Medical Oncology), ASCO, and NCCN guidelines recommend against routine use of G-CSFs for patients with established febrile neutropenia.40,41,44 However, use of G-CSFs can be considered for patients with high-risk features such as hospital duration >10 days, profound neutropenia (with <100 cells/μL), age >65, multiorgan dysfunction, and hypotension.

Fluid retention

Docetaxel therapy frequently triggers fluid retention presenting as swelling of the extremities, pleural effusions, ascites, and pericardial effusion. One of the proposed mechanisms underlying this adverse effect is increased permeability of the capillaries resulting in leakage of fluid into the surrounding tissue.45 The severity of this reaction is proportional to the cumulative dose of the drug administered. Premedication with glucocorticoid starting 24 hours prior and 48 hours following each docetaxel dose decreases the rate of fluid retention from 20% to 6% and increases the tolerability of this drug among patients.46 Studies have indicated that a single dose of dexamethasone, rather than the standard 3 doses, may be sufficient to prevent docetaxel-fluid retention.47,48 Patients should be advised to monitor for signs of increased fluid accumulation in their fingers, ankles, and mid-abdominal areas. Treatment with diuretics may provide symptomatic relief and limit the severity of fluid retention.49

Cutaneous toxicity

Docetaxel is also known to cause a skin toxicity known as acral erythema. It often starts with a tingling sensation in the palms and soles, followed by tenderness and edema. Occasional desquamation and blistering in the affected area may also occur. The pathogenesis of acral erythema remains unclear. Proposed mechanisms include immunoglobulin E-mediated type 1 reaction and direct toxic effect of chemotherapy on the eccrine sweat glands.50 Treatment of acral erythema mainly includes cessation of drug and symptomatic treatment to relieve the painful swelling and erythema. In addition, intravenous docetaxel has also been associated with a specific variant of acral erythema known as erythrodysesthesia plaque that presents as a fixed, solitary plaque proximal to the infusion site without involvement of the palms and soles. The characteristic lesion typically resolves with desquamation followed by hyperpigmentation weeks after the initial insult.51,52

Nail toxicity

Docetaxel can cause a wide range of nail toxicities including subungual and splinter hemorrhages, hyperkeratosis, paronychia, separation of the nail from the nail bed, and cessation of nail growth. The severity of the nail changes correlates with the total number of chemotherapy cycles and the cumulative dose of chemotherapy administered. Studies have indicated that the use of frozen gloves and socks can slow the onset and lower the severity of symptoms in a large proportion of patients by reducing blood flow to the affected areas.53,54 The majority of the symptoms resolve spontaneously within 6–12 months after chemotherapy discontinuation.

Pneumonitis

Docetaxel has been rarely reported to cause acute, bilateral interstitial lung disease that can occur during, within a few hours, or up to weeks after initial administration. Symptoms include exertional dyspnea, dry cough, malaise, and fever.55 The mechanism behind interstitial pneumonitis is not well understood at the present time. Some researchers believe that it is predominantly a lymphocyte-mediated immune reaction.33 In contrast to paclitaxel, the incidence of pulmonary toxicity is proportional to the total dose of docetaxel administered. In a Phase III trial of women with advanced breast cancer, a statistically significant higher rate of pulmonary toxicity was observed with higher docetaxel doses (100 mg/m2 in comparison with 60 mg/m2).56 Moreover, a higher incidence of pneumonitis was seen in patients receiving weekly versus every 3 weeks docetaxel regimen.57 The rate of pulmonary toxicity is also higher when docetaxel is given in combination with gemcitabine or radiation.5860 Patients with preexisting lung disease are at a higher risk of developing pulmonary complications with docetaxel treatment. Therefore, taxane treatment is relatively contraindicated in patients with preexisting lung disease.61 Fortunately, most cases resolve with supportive care and discontinuation of taxane therapy. For patients with clinical signs of oxygen desaturation or impending respiratory failure, an empiric trial of glucocorticoids may be warranted.

Fatigue

Most patients receiving docetaxel chemotherapy will experience fatigue during the course of their treatment. Research indicates that continuous exercise may help to delay the onset of fatigue and optimize physical function.62,63 To date, no studies have been conducted on the management of docetaxel-related fatigue. Other common causes of asthenia such as depression, pain, anemia, and hypothyroidism must also be considered and treated accordingly.

Epiphora and lacrimal duct stenosis

Epiphora (excessive tearing) is a frequent complaint of breast cancer patients receiving docetaxel. Although most patients treated with short courses of adjuvant docetaxel find this is a self-limited problem that resolves soon after completion of docetaxel chemotherapy, it is particularly frequent and severe in those receiving prolonged docetaxel therapy in the metastatic setting and those treated with weekly docetaxel. In some cases, canalicular fibrosis requiring surgical stenting has been identified.6466

Gastrointestinal complications

Cases of gastrointestinal perforation, and dehydration as a consequence of enterocolitis, colitis, and neutropenic enterocolitis have been reported in breast cancer patients receiving docetaxel. Patients receiving this agent should be carefully evaluated if severe diarrhea or new onset abdominal pain occurs, and surgical consultation is warranted in patients with severe enterocolitis or demonstrated perforation.67,68

Long term side effects

Neuropathies

Two of the most common long-term side effects of docetaxel chemotherapy are sensory and motor peripheral neuropathy. Fortunately, the incidence of both of these is much less than paclitaxel. Grade 3 and 4 neuropathy is only observed in less than 10% of patients receiving docetaxel therapy.69,70 Major clinical symptoms include numbness and tingling of the hands and feet, with loss of reflexes. The incidence of neuropathy is dependent upon the total dose of the drug administered. In the Phase III clinical trial of metastatic breast cancer patients treated with docetaxel, neuropathy of grade 2 or greater began at a dosage of 371 mg/m2.71 The mainstay of treatment includes prompt recognition of onset of symptoms with subsequent delay of therapy or dose reduction. Unfortunately, none of the pharmaceutical agents have demonstrated efficacy in the prevention and treatment of taxane-induced neuropathy. Anticonvulsants such as gabapentin may be useful in providing symptomatic relief.72

Conclusion

Docetaxel is an effective chemotherapeutic agent for the treatment of breast cancer in the adjuvant, neoadjuvant, and metastatic settings. Its widespread use has contributed to improvements in breast cancer-specific survival seen in many developed countries. Even though the drug can cause a wide range of toxicities, most of them are treatable with supportive care and cessation of the chemotherapeutic agent. The decision to initiate chemotherapy should always be made in partnership with the patient, who should be fully informed about the potential side effects of the treatment.

Footnotes

Disclosure

The authors have no conflicts of interest to disclose.

References

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Docetaxel | DrugBank Online

Injection Parenteral
Injection
Solution / drops Ophthalmic
Solution
Kit Intravenous 20 mg/0.8mL
Kit Intravenous 80 mg/4mL
Powder Intravenous
Injection Intravenous 160 mg/8mL
Injection Intravenous 80 mg/4mL
Injection, solution Intravenous 10 mg/1mL
Injection, solution Intravenous 160 mg/8mL
Injection, solution Intravenous 20 mg/1mL
Injection, solution Intravenous 80 mg/4mL
Injection, solution, concentrate Intravenous 160 mg/8mL
Injection, solution, concentrate Intravenous 20 mg/1mL
Injection, solution, concentrate Intravenous 20 mg/2mL
Injection, solution, concentrate Intravenous 200 mg/20mL
Injection, solution, concentrate Intravenous 80 mg/8mL
Kit Intravenous 40 mg/1mL
Solution Intravenous 20 mg/1mL
Solution Parenteral
Solution, concentrate Intravenous
Injection, solution Intravenous 160 mg/16mL
Injection, solution Intravenous 20 mg/2mL
Injection, solution Intravenous 80 mg/8mL
Injection, solution, concentrate Intravenous; Parenteral
Injection Intravenous 20 mg/1mL
Injection, powder, lyophilized, for solution Parenteral
Injection, powder, lyophilized, for solution Intravenous
Injection, solution, concentrate Intravenous
Injection, solution, concentrate
Injection, powder, for solution Intravenous
Solution Parenteral 80 mg
Injection Intravenous
Solution Intravenous
Kit; solution Intravenous
Solution Intravenous 20 mg
Solution Intravenous 80 mg
Injection, solution, concentrate Intravenous 40 mg/1mL
Injection, solution, concentrate Intravenous 80 mg/4mL
Injection, solution Intravenous
Solution, concentrate Intravenous 20 mg
Solution, concentrate Intravenous 80 mg
Injection, solution Intravenous 40 mg/1ml

90,000 contraindications, side effects, dosages, composition – concentrate for pre-prepared solution and for infusions in the reference book of medicines

Treatment with docetaxel should be carried out only under the supervision of a physician with experience in anticancer chemotherapy in a specialized hospital.

Docetaxel is not used when the content of bilirubin is more than VGN in combination with the activity of hepatic transaminases, which exceeds the VGN by 1.5 times, and the alkaline phosphatase exceeds the VGN by 2.5 times.

Before starting therapy with docetaxel, patients are prescribed oral corticosteroids. The likelihood of developing allergic reactions and the occurrence of edema is significantly increased in patients who have not previously received such therapy.

During the treatment period, systematic monitoring of the peripheral blood picture is necessary in order to identify the degree of myelodepression.

CBC should be monitored in patients receiving docetaxel therapy. The maximum decrease in neutrophils occurs by 7 days, but in patients who have previously received intensive chemotherapy, this interval may be shorter.With the development of severe neutropenia (<500 / μl for 7 days) during the course of docetaxel, it is recommended to reduce its dose in subsequent cycles or apply adequate symptomatic measures. Docetaxel treatment may be continued after neutrophil counts have recovered> 1500 / μL.

Docetaxel should be used with caution in neutropenic patients, especially at risk of gastrointestinal complications. The development of enterocolitis is possible throughout the treatment. Enterocolitis can lead to death even on the first day of its development.

In order to detect the development of a hypersensitivity reaction, patients should be carefully monitored, especially during the first and second infusion. The development of hypersensitivity reactions is possible in the very first minutes of docetaxel infusion, therefore, when it is administered, it is necessary to have drugs and equipment for the treatment of arterial hypotension and bronchospasm.

In patients receiving monotherapy with docetaxel at a dose of 100 mg / m 2 and having an increased activity of hepatic transaminases (ALT and / or ACT), more than 1.5 times higher than ULN, in combination with an increase in ALP activity, more than 2.5 times higher than ULN, the risk of developing severe side effects, such as sepsis, gastrointestinal bleeding, febrile neutropenia, infections, thrombocytopenia, severe toxic skin lesions up to death, as well as stomatitis and asthenia, is extremely high.Liver function tests should be performed before starting treatment and before each subsequent cycle of docetaxel therapy.

Careful monitoring of patients with severe fluid retention is necessary: ​​

  • with pleural effusion, pericardium, or with ascites. When edema appears, restriction of salt and drinking regimen and the use of diuretics are indicated.

In patients 65 years of age and older who received treatment with docetaxel every 3 weeks for prostate cancer, the frequency of nail changes, anemia, infections, anorexia, and body weight loss was> 10% higher than in younger patients. and in patients 75 years of age and older, the incidence of fever, diarrhea, anorexia, and peripheral edema was> 10% higher than in younger patients.There were no differences in the effectiveness of therapy when comparing older and younger patients.

Men and women of childbearing age should use reliable methods of contraception during treatment with docetaxel. Men receiving docetaxel treatment are advised to refrain from conceiving a child during docetaxel treatment and for at least 6 months after the end of chemotherapy.

Influence on the ability to drive vehicles and use mechanisms

During the period of treatment, patients should avoid driving vehicles and other activities that require high concentration of attention and speed of psychomotor reactions.

Taxanes as first and second lines of chemotherapy for metastatic prostate cancer

S.V. MISHUGIN , T.N. SKVORTSOVA , I.G. RUSAKOV , MD, professor, GBUZ GKB No. 57, Moscow

Prostate cancer (PC) is one of the most common oncological diseases in men. More than 600 thousand new cases are registered in the world annually, and in a number of countries where its incidence is highest (USA, Canada, northern Europe), it came out on top in the structure of cancer incidence in the male population [1, 2].

In the Russian Federation in the last decade, there has been a significant increase in the incidence of prostate cancer: if in 2000, 11,580 newly diagnosed patients were registered, then in 2011 – 28,552. Unfortunately, in more than half of patients, the disease is diagnosed in already widespread forms , in the treatment of which hormone therapy (HT) takes the main place [3].

By means of androgen blockade it is possible to achieve stabilization of the process in more than 80% of patients, but the average time to progression after hormone therapy in metastatic prostate cancer is only about 2 years [4].

Despite the castration level of testosterone, almost 80% of these patients within 12-24 months. the progression of the disease occurs with the ascertaining of the castrate-refractory form [5].

The group of these men is characterized by the lack of effect from standard hormonal treatment: an increase in PSA against the background of castration testosterone levels, progression from the affected lymph nodes and / or bone and visceral metastases. Their average life expectancy without additional therapy does not exceed 6–12 months.[6].

Modern chemotherapeutic drugs demonstrate their effectiveness in reducing PSA levels, regression from loco-regional lesions and metastatic foci, improve the quality of life of patients, increase the time to progression and increase overall survival [7].

The FDA approved combination of mitoxantrone and prednisolone was the “gold standard” of therapy before taxanes appeared, but it was found that this regimen provides only symptomatic effect, with little or no effect on disease-free survival and life expectancy. patients [8].

In 2008, a randomized phase III trial TAX 327 was completed, which included an analysis of the therapy of 1,006 patients with metastatic HRP [9].

This large, randomized, multicenter study compared 2 different docetaxel regimens and the combination of mitoxantrone and prednisolone.

All patients were randomized into groups:

1) docetaxel (Taxotere®) 30 mg / m2 weekly 5 injections every 6 weeks;
2) docetaxel (Taxotere®) 75 mg / m2 every 3 weeks and
3) mitoxantrone 12 mg / m2 every 3 weeks.

Patients of all three groups additionally received prednisolone. The median life expectancy was 19.2 months. in the 3-week docetaxel group, 17.8 months – in the group of weekly use of docetaxel and 16.3 months. – in the group of application of mitoxantrone. In 22% of patients treated with docetaxel every 3 weeks, there was a significant improvement in quality of life, in 45% of patients treated with 3-week docetaxel, there was a decrease in PSA by 50%.

Side effects of docetaxel included grade III – IV neutropenia, which occurred in 32% of patients who received docetaxel every 3 weeks and only 1.5% of patients who received this drug weekly.Other side effects included weakness, alopecia, diarrhea, neuropathy, peripheral edema, and decreased sexual function.

It was concluded that the 3-week regimen of docetaxel administration is superior to the mitoxantrone plus prednisone regimen in terms of increased survival, lower PSA levels, reduced pain, and improved quality of life [10].

Similar results were obtained in a domestic study (TANDEM) with a similar design [11].
• The desire to increase the possibilities of modern chemotherapy by combining it with additional HT facilitated the organization of the SWOG study 9916 [12], the results of which were published in 2004

• After randomization into two groups, men with castrate-refractory prostate cancer were treated:
– 1st group – Taxotere® at a dose of 60 mg / m2 on the 2nd day, estramustine – 280 mg orally 3 times a day from the 1st to the 5th day every 3 weeks;
– 2nd group – mitoxantrone at a dose of 12 mg / m2 every 3 weeks against the background of prednisolone – 5 mg 2 r / day for a long time.

This study revealed a significant improvement in the long-term results of treatment in patients receiving Taxotere therapy in combination with estramustine (life expectancy – 17.5 months in the 1st group and 15.6 months in the 2nd, p = 0 , 02; time to progression – 6.3 and 3.2 months, respectively, p <0.001), however, an increase in toxicity due to the inclusion of estrogen in the treatment regimen and the need to reduce the dose of cytostatic did not allow recommending this option for wide clinical use, although the combination cytostatic with another variant of hormonal deprivation therapy is recognized by most authors as appropriate.

We conducted a study, which included 60 patients with HRPC. Two groups of patients were identified:

1st group (n = 31) – patients received Taxotere® at a dose of 75 mg / m2 every 3 weeks + LHRH agonists
Group 2 (n = 29) – patients received Taxotere monotherapy at a dose of 75 mg / m2 every 3 weeks. The serum testosterone level in all these patients before inclusion in the study was significantly higher than castration, (1.7 nmol / L), since they all received antiandrogens (bicalutamide) in a high dose for at least 3 months after registering castrate resistance, and after that a month carried out without hormonal therapy to register the “withdrawal syndrome”.

In both groups, the patients were approximately comparable in age, the nature of the previous treatment and the degree of tumor differentiation; in the nature of bone metastasis, most of the patients in both groups met the Soloway 3-4 criteria.

Ensuring a high quality of life for patients with HRPC is a decisive factor in choosing a treatment regimen. Therefore, the level of pain syndrome and activity status were assessed as components of the quality of life. The level of pain grade was assessed according to the WHO 4-point scale, the assessment of the general condition was assessed by the Karnovsky system.

The use of Taxotere in combination with aLHRH made it possible to increase the activity status in five (16.1%) patients of the first group and in three (10.3%) patients in the second group (p = 0.06). The level of pain syndrome was reduced in 41.9% and 37.9% (p <0.05) of patients, respectively. All this testifies to the positive effect of therapy on the quality of life of patients.

A positive response to therapy in the form of a decrease in PSA by more than 50% was noted in an equal number of patients – 11 in each group, but if this decrease occurred in the first group in most patients (10) after the 2nd and 3rd courses , then in the second group in 6 patients this effect was observed only after the 4th and 5th courses of docetaxel.

Progression of the tumor process in the form of the appearance of additional foci after 6 months. after the start of chemotherapy was observed in 9 patients of the first group and in 13 patients of the second group.

The average life expectancy of patients who did not receive the next line of therapy was 15.5 months. in the 1st group and 13.6 months. – in the 2nd.
In recent years, searches have continued to modify the structure of taxane derivatives, which would have an additional antitumor effect after the development of resistance to known drugs.As a result of a slight modification in the structure, a new drug was created – cabazitaxel (Jevtana®), which overcomes resistance to cell cultures in vivo and in vitro and showed activity in models of docetaxel-sensitive and docetaxel-resistant cells.

Its ability to overcome the blood-brain barrier and to be effective in affecting the spine and spinal cord (antitumor activity) has been established, a good symptomatic effect has been noted [13, 14].

A Phase 3 Randomized Multicenter Study – Hormone-Refractory Metastatic Prostate Cancer Previously Treated with a Taxotere-containing Regimen (TROPIC) comparing the efficacy of cabazitaxel with mitoxantrone in metastatic docetaxel-resistant PCa, showed that cabazitaxel was significantly increase the median overall survival (15.1 months versus 12.7 months), reduce the risk of death by 30% [15].

After 2 years from the beginning of treatment with cabazitaxel, 28% of patients were alive, while in the group of patients receiving mitoxantrone, only 17% of patients survived by this time.The median time without radiological progression of the disease was significantly lengthened – 8.8 months. compared with 5.4 months. in the control group (p <0.0001) [15].

In this study, a rather high hematological toxicity of the drug was noted, manifested in the form of the development of febrile neutropenia (7.5%). However, a number of studies (for example, the German Compassionate Use Program – GUP) have shown that the implementation of the recommendations of the American Society of Clinical Oncology for the prophylactic administration of stimulants of leukopoiesis provides more than a twofold decrease in the likelihood of developing this complication [16].

Under our supervision since October 2012, there were 18 patients who received from six to nine courses of docetaxel (11 – under conditions of medical castration and 6 – without the use of blood pressure). In 17 of them, the progression of the tumor process was noted – the appearance of new bone foci in 7 patients, in two iliac and para-aortic enlarged lymph nodes were identified and morphologically verified, in one patient metastases in the lungs appeared, in the remaining 7 patients – a persistent increase in PSA against the background therapy (more than 6 months.). In one patient, the reason for discontinuation of docetaxel treatment was severe polyneuropathy after 7 courses, although the PSA level remained stable.

Eight patients continue to receive cabazitaxel treatment against the background of positive PSA dynamics for an interval of 8 to 3 months, five patients showed stabilization for 4-6 months, after which progression was noted, another five patients were transferred to other treatment options against the background of registration of PSA growth after three courses of treatment with Dzhevtana.

A decrease in the level of leukocytes was noted in all patients who received more than two courses of cabazitaxel, however, the appointment of leukopoiesis stimulants already at the first signs of leukopenia made it possible to avoid serious complications – leukopenia 3-4 tbsp. observed only in 5 patients without significant consequences.

There were no cases of febrile neutropenia in our observations. None of the patients receiving cabazitaxel (Jevtana) were discontinued due to toxic complications.

Thus, sequential administration of taxanes – docetaxel (Taxotere®) in the first line and cabazitaxel (Jevtana®) in the second – allows to increase the life expectancy of patients with metastatic prostate cancer and improve their quality of life.

First-line cytostatic therapy is advisable to carry out while continuing castration therapy.

REFERENCES
1. Jemal A., Siegel R., Ward E. et al. Cancer statistics. 2008. CA Cancer // J.Clin. 2008. No. 58 (2). R. 71–96.
2.http: //www.seer.cancer.gov/statfacts/html/prost.html (accessed April 12, 2011).
3. Malignant neoplasms in Russia in 2011 // ed. IN AND. Chissova, V.V. Starinsky, G.V. Petrova. 2013.
4. Prostate Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up // Ann. Oncol. 2012.
5. Alekseev B.Ya., Andrianov A.N. Possibilities and mechanisms of action of hormonal therapy in patients with castration-resistant prostate cancer // Oncourology.2113. # 1. S. 34–43.
6. Kish J., Bukkapatnam R. et al. The treatment challenge of hormone-refractory prostate cancer // Cancer Care. 2001. No. 8 (6). R. 487-495.
7. Harris K.A., Reese D.M. Treatment options in hormone-refractory prostate cancer: current and future approaches // Drugs. 2001. No. 61. R. 2177-2192.
8. Kantoff P. W., Halabi S., Conaway M. et al. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study // J.Clin. Oncol. 1999. No. 17. R. 2506-2513.
9. Berthold D.R. et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study // J. Clin. Oncol. 2008. No. 10. 26 (2). R. 242–245.
10. Tannok I.F., de Wit R., Berry W.R. et al. Docetaxel plus prednisolone for advanced prostate cancer // N. Engl. J. Med. 2004. No. 351. R. 1502-1512.
11. Karjakin O.B. [et al.] Russian experience of using Taxotere in the treatment of metastatic hormone-refractory prostate cancer: results of the descriptive study TANDEM // Oncourology.2010. No. 4. S. 61–64.
12. Petrylak D.P. et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer // N. Engl. J. Med. 2004. # 7; 351 (15). R. 1513-1520.
13. Paller Channing J., Antonarakis Emmanuel S. Cabazitaxel: a novel second-line treatment for metastatic castration-resistant prostate cancer // Drug. Des Devel. Ther. 2011. No. 5. R. 117-124.
14. Wilkes G. Cabazitaxel, a taxane for men with hormone-refractory metastatic prostate cancer // Oncology (Williston Park).2010. No. 24 (Suppl. 10). R. 46–48.
15. De Bono J. S., Oudard S., Ozguroglu M. et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomized open-label trial // Lancet. 2010. No. 376 (9747). R. 1147-1154.
16. Heidenreich A., Scholzb H., Rogenhoferc S. et al. Cabazitaxel Plus Prednisone for Metastatic Castration-resistant Prostate Cancer Progressing After Docetaxel: Results from the German Compassionate-use Program // European Urology.June 2013. Vol. 63. Is. 6.R. 977-982.

Anhydrous docetaxel – 2 reviews, instructions, analogs, price 18662 rubles.

Active ingredient : Docetaxel check compatibility

Attention! Medicines are dummies – how Russians are bred or what money should not be spent on!

Names
Russian name: Anhydrous docetaxel.
English name: Docetaxel anhydrous.

Component contraindications
Docetaxel contraindications.Hypersensitivity, neutropenia (9 / l), severe liver dysfunction (increased levels of bilirubin, transaminases, alkaline phosphatase – see “Precautions”). Use of the drug Docetaxel when breastfeeding. Contraindicated in pregnancy.
FDA Fetal Activity Category. D.
During treatment, breastfeeding should be discontinued (it is unknown whether docetaxel passes into breast milk).

Side effects of the ingredients
Side effects of Docetaxel.From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): neutropenia, thrombocytopenia, anemia; heart rhythm disturbances, heart failure, lowering or increasing blood pressure, cases of venous thromboembolism and myocardial infarction.
From the digestive tract. Nausea. Vomiting. Diarrhea / constipation. Anorexia. Stomatitis. Disturbance of taste. Esophagitis. Pain in the stomach. Increased serum AST levels. ALT. ALF. Hyperbilirubinemia; cases of gastrointestinal bleeding.
From the skin side. Alopecia; skin rash, often accompanied by itching, sometimes with subsequent desquamation, leading in some cases to interruption or discontinuation of docetaxel therapy; hypo – or hyperpigmentation of nails and onycholysis.
Allergic reactions. Mild to moderate hypersensitivity reactions (flushing of the face. Rash combined with itching. Chest tightness. Back pain. Shortness of breath and drug fever or chills).Severe reactions (accompanied by arterial hypotension and / or bronchospasm or generalized rash / Erythema) – see “Precautions”.
Others. Peripheral neuropathy (paresthesia. Dysesthesia or pain. Weakness). Peripheral edema (initially usually appears on the lower extremities). Ascites. Asthenia. Arthralgia and myalgia. Reactions at the injection site (hyperpigmentation. Inflammation. Redness or dryness of the skin. Phlebitis. Hemorrhage or swelling of a vein). Updating information.
As of July 31, 2012. Health Canada received 31 reports of respiratory adverse reactions. Possibly related to the use of docetaxel. Among which are pneumonitis. Interstitial lung disease. Lung infiltration or respiratory failure – 23 patients required hospitalization. Death was reported in 9 cases.
Several cases of serious respiratory adverse reactions have been reported in the literature in patients using docetaxel either alone or in combination with other antineoplastic agents.These adverse reactions include pneumonitis or interstitial pneumonitis, pulmonary infiltrates, acute respiratory distress syndrome, respiratory failure, interstitial lung disease, interstitial infiltrates, and Pneumocystis pneumonia. Some of these cases have been fatal.
Source of information.
Whoint [Updated. 05.09.2013].

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Docetaxel Ebeve®

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Trade name of the drug : Docetaxel Ebeve®
(Docetaxel)

Active ingredients : Docetaxel

Pharmacotherapeutic group : Antineoplastic agent, Antineoplastic agent

Release form :

A vial made of colorless glass I with a hydrolytic cork and a caucholytic cork crimp cap with or without ONCO-SAFE protective plastic cap.Packaged:
1 bottle of 20 mg / 2 ml
1 bottle of 80 mg / 8 ml
1 bottle of 160 mg / 16 ml.

Dosage form :

Concentrate for preparation of solution for infusion 10 mg / ml, 20 mg / 2 ml; 80 mg / 8 ml (vials)

Composition :

1 ml of concentrate for solution for infusion contains 10 mg of docetaxel.
1 bottle of concentrate for solution for infusion contains docetaxel in the form of trihydrate, which corresponds to 20 mg or 80 mg of docetaxel (anhydrous).1 bottle with 2 ml of the drug contains 20 mg of docetaxel (10 mg / ml).
1 bottle with 8 ml of the drug contains 80 mg of docetaxel (10 mg / ml).
1 bottle with 16 ml of the drug contains 160 mg of docetaxel (10 mg / ml).

The preparation contains an excipient: 27% (v / v) ethanol 96%.
Auxiliary ingredients
Citric acid anhydrous
Macrogol 300
Polysorbate 80
Ethanol (see section 4.4)

Pharmacokinetics :

The pharmacokinetics of docetaxel was studied in cancer patients who received the drug at doses of 20-115 mg / m2 body surface during phase I studies.Population pharmacokinetic analysis of data on 577 patients showed that the pharmacokinetics of docetaxel does not depend on the age and sex of the patient. The pharmacokinetic parameters described by the model were very close to those obtained in phase I studies.
Absorption
After the introduction of docetaxel at a dose of 100 mg / m2 of body surface by a one-hour intravenous infusion, the maximum concentration of docetaxel in the blood plasma was 3.7 μg / ml, and the area under the pharmacokinetic curve (AUC) was 4.6 h ∙ μg / ml.Distribution
The pharmacokinetic profile of docetaxel is dose-independent and is described by a three-chamber model. The half-lives in the alpha, beta and gamma phase are 4 minutes, 36 minutes and 11.1 hours, respectively. The prolonged terminal phase is partly due to the relatively slow release of docetaxel from the peripheral chamber.
More than 96% of docetaxel binds to blood plasma proteins.
Elimination
The average indicators of the total clearance and the equilibrium volume of distribution were, respectively, 21 l / h ∙ m2 and 113 liters.Interindividual variability in total clearance was approximately 50%.
A study with the introduction of 14C-docetaxel was conducted on three cancer patients. Docetaxel was excreted in urine and feces within 7 days after P450-mediated oxidative metabolism of the tert-butyl ester group. Excretion in urine and feces was 6% and 75% of the dose, respectively. Approximately 80% of the radioactivity found in feces was excreted within 48 hours as the main inactive metabolite and three minor inactive metabolites.Docetaxel was found unchanged in the feces in very small amounts.
In a small number of patients (n = 23) with mild or moderate liver dysfunction (ALT and AST levels are more than 1.5 times higher than ULN in combination with an increase in alkaline phosphatase activity more than 2.5 times higher than ULN), the total clearance of docetaxel was 27% below average (see section 4.2). Docetaxel clearance did not differ from the mean in patients with mild to moderate fluid retention; there is no information on drug clearance in patients with severe fluid retention.Pharmacokinetic interaction with other drugs
With combined chemotherapy, docetaxel does not affect the clearance of doxorubicin and the plasma level of doxorubicinol (a metabolite of doxorubicin). The pharmacokinetic parameters of docetaxel, doxorubicin and cyclophosphamide do not change with their simultaneous use.
A phase I clinical study, which examined the mutual effect of capecitabine and docetaxel on the pharmacokinetics of each other, showed no effect of capecitabine on the pharmacokinetics of docetaxel (judging by Cmax and AUC) and no effect of docetaxel on the pharmacokinetics of the metabolite of capecitabine 5 ‘DFUR.The clearance of docetaxel in combination therapy with cisplatin is comparable to that of docetaxel alone. When cisplatin is given shortly after docetaxel, its pharmacokinetic profile is comparable to that of cisplatin alone.
A study on 12 patients with solid tumors did not reveal a mutual influence on the pharmacokinetics of each other’s docetaxel, cisplatin and 5-fluorouracil with this combination chemotherapy.
The study of the effect of prednisone on the pharmacokinetics of docetaxel in 42 patients who received standard premedication with dexamethasone did not reveal any changes in the pharmacokinetics of docetaxel.Docetaxel is an antineoplastic agent that promotes the formation of stable microtubules from tubulin and inhibits their breakdown, which leads to a pronounced decrease in the concentration of free tubulin. Binding of docetaxel to microtubules does not affect the number of protofilaments.
In vitro studies have shown that docetaxel damages the microtubular network in cells and thus disrupts cellular functions during the interphase and mitotic stages.
In vitro studies have shown that docetaxel has a cytotoxic effect against various tumor cell lines in mice and humans, as well as freshly isolated human tumor cells in clonogenic assays.Intracellular concentrations of docetaxel reach high levels and persist over time. In addition, docetaxel has been shown to be active against some, though not all, cell lines with overexpression of the p-glycoprotein encoded by the multiple resistance gene. In vivo, docetaxel has a wide spectrum of antitumor activity (regardless of the regimen) against common tumors of mice and transplanted human tumors.

Indications for use :

Breast cancer
Docetaxel Ebeve in combination with doxorubicin and cyclophosphamide is used for the adjuvant therapy of patients with resectable breast cancer with lymph node involvement.Docetaxel Ebeve in combination with doxorubicin is used to treat patients with locally advanced or metastatic breast cancer who have not previously received cytotoxic chemotherapy for this condition.
Docetaxel Ebeve as monotherapy is used to treat patients with locally advanced or metastatic breast cancer in case of failure of previous cytotoxic chemotherapy, including anthracyclines or alkylating drugs.
Docetaxel Ebeve in combination with trastuzumab is used to treat patients with metastatic breast cancer with overexpression of the HER-2 oncogene who have not previously received chemotherapy for metastases.Docetaxel Ebeve in combination with capecitabine is used to treat patients with locally advanced or metastatic breast cancer in case of failure of previous cytotoxic chemotherapy, including anthracyclines. Non-small cell lung cancer
Docetaxel Ebeve is used to treat patients with locally advanced or metastatic non-small cell lung cancer if previous chemotherapy has failed.
Docetaxel Ebeve in combination with cisplatin is used to treat patients with unresectable, locally advanced, or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition.Prostate cancer
Docetaxel Ebeve in combination with prednisone or prednisolone is used to treat patients with hormone-refractory metastatic prostate cancer.
Adenocarcinoma of the stomach
Docetaxel Ebeve in combination with cisplatin and 5-fluorouracil is used to treat patients with metastatic adenocarcinoma of the stomach, including adenocarcinoma of the gastroesophageal junction, who have not previously received chemotherapy for metastases.
Head and neck cancer
Docetaxel Ebeve in combination with cisplatin and 5-fluorouracil is used for induction therapy in patients with locally advanced squamous cell carcinoma of the head and neck.

Route of administration :

Treatment with docetaxel should be carried out under the supervision of an oncologist in a specialized hospital (see section 6.6).
For breast cancer, non-small cell lung cancer, stomach cancer, as well as head and neck cancer, in the absence of contraindications, oral premedication with corticosteroids, for example, dexamethasone at a dose of 16 mg / day (8 mg 2 times a day), can be performed for 3 days, starting 1 day before the administration of docetaxel (see.section 4.4). In order to prevent hematological toxicity, granulocyte colony-stimulating factor (G-CSF) can be used.
For prostate cancer patients receiving concomitant prednisone or prednisolone therapy, oral premedication with dexamethasone 8 mg is recommended 12 hours, 3 hours, and 1 hour before docetaxel (see section 4.4).
Docetaxel Ebeve is administered as a one-hour intravenous infusion every 3 weeks. Recommendations regarding the preparation of solutions for infusion are given in section 6.6.
Measures should be taken to prevent perivenous extravasation.

Recommended doses
Mammary cancer
In the adjuvant therapy of operable breast cancer with damage to the lymph nodes, Docetaxel Ebeve is recommended to be administered at a dose of 75 mg / m2 of body surface 1 hour after administration of doxorubicin at a dose of 50 mg / m2 and cyclophosphamide at a dose of 500 mg / m2 of body surface. The courses of treatment are repeated at intervals of 3 weeks, a total of 6 courses are carried out (see also recommendations for adjusting doses during treatment).When monotherapy for locally advanced or metastatic breast cancer, Docetaxel Ebeve is recommended to be administered at a dose of 100 mg / m2 of body surface.
For first-line therapy of locally advanced or metastatic breast cancer, Docetaxel Ebeve is used at a dose of 75 mg / m2 of body surface in combination with doxorubicin at a dose of 50 mg / m2 of body surface.
In combination with trastuzumab Docetaxel Ebeve is recommended to be administered at a dose of 100 mg / m2 of body surface every 3 weeks, and trastuzumab – weekly.In a pivotal clinical trial, the first infusion of docetaxel was given the day after the first dose of trastuzumab. Subsequently, docetaxel was administered immediately after completion of the trastuzumab infusion, provided that the previous dose of trastuzumab was well tolerated. Recommendations regarding the dosage and route of administration of trastuzumab are given in the appropriate instructions for use of the drug.
In combination with capecitabine Docetaxel Ebeve is recommended to be administered at a dose of 75 mg / m2 of body surface every 3 weeks, and capecitabine at a dose of 1250 mg / m2 of body surface twice a day (30 minutes after a meal) for two weeks, followed by a week break …Refer to the capecitabine instructions for use for guidance on how to dose capecitabine based on patient surface area.
Non-small cell lung cancer
For first-line chemotherapy of non-small cell lung cancer, Docetaxel Ebeve is recommended to be administered at a dose of 75 mg / m2 of body surface, followed by immediate administration of cisplatin at a dose of 75 mg / m2 of body surface by intravenous infusion for 30-60 minutes.
In case of ineffectiveness of previous chemotherapy with platinum preparations, Docetaxel Ebeve is used as monotherapy at a dose of 75 mg / m2 of body surface.Prostate cancer
Docetaxel Ebeve is recommended to be used at a dose of 75 mg / m2 of body surface in combination with prednisone or prednisolone 5 mg orally 2 times a day for a long time (see section 5.1).
Adenocarcinoma of the stomach
Docetaxel Ebeve is recommended to be administered at a dose of 75 mg / m2 of body surface by intravenous infusion for 1 hour, after which cisplatin is administered at a dose of 75 mg / m2 of body surface by intravenous infusion for 1-3 hours (both drugs are administered on the first day of the course), and then 5 fluorouracil at a dose of 750 mg / m2 of body surface per day by 24-hour continuous infusion for 5 days, starting from the end of the cisplatin infusion.The courses of treatment are repeated at intervals of 3 weeks. It is necessary to premedication with antiemetics and appropriate hydration in connection with the administration of cisplatin. In order to prevent hematological toxicity, G-CSF should be used (see also recommendations for dose adjustment during treatment).
Head and neck cancer
It is necessary to premedication with antiemetics and appropriate hydration (before and after the administration of cisplatin). In order to prevent hematological toxicity, G-CSF can be used.All patients who received docetaxel in the TAX 323 and TAX 324 trials received antibiotic prophylaxis.
• Induction chemotherapy followed by radiation therapy (TAX 323 regimen)
For induction therapy of inoperable locally advanced squamous cell carcinoma of the head and neck, Docetaxel Ebeve is recommended to be administered at a dose of 75 mg / m2 of body surface by intravenous infusion for 1 hour, after which cisplatin is administered at a dose of 75 mg / m2 of body surface by intravenous infusion for 1 hour ( both drugs are administered on the first day of the course), and then 5 fluorouracil at a dose of 750 mg / m2 of body surface per day by 24-hour continuous infusion for 5 days.In total, 4 courses of treatment are carried out with a frequency of 3 weeks. After chemotherapy ends, patients receive radiation therapy.
• Induction chemotherapy followed by chemoradiotherapy (TAX 324 regimen)
When induction therapy is technically unresectable (with a low probability of surgical cure, in order to preserve organs) locally advanced squamous cell carcinoma of the head and neck, Docetaxel Ebeve is recommended to be administered at a dose of 75 mg / m2 of body surface by intravenous infusion for 1 hour on the first day of the course, after which cisplatin is administered at a dose of 100 mg / m2 of body surface by intravenous infusion lasting from 30 minutes to 3 hours, and then 5 fluorouracil at a dose of 1000 mg / m2 of body surface per day by 24-hour continuous infusion from the first to the fourth day.In total, 3 courses of treatment are carried out with a frequency of 3 weeks. After the end of chemotherapy, patients receive chemoradiation therapy.
Recommendations for dose adjustment of cisplatin and 5-fluorouracil are given in the respective instructions for use of the drugs.
Dose adjustments during treatment
General recommendations
Docetaxel Ebeve can be used only if the number of neutrophils in the peripheral blood exceeds 1500 cells / mm3. If febrile neutropenia develops during treatment with docetaxel, with duration of neutropenia ( Side effects :

Depending on the frequency, side effects are divided into the following groups: very frequent (≥ 1/10), frequent (≥ 1/100 – Contraindications :

• Hypersensitivity to the active substance or other ingredients of the preparation.• Initial number of neutrophils Drug interaction :

In vitro studies have shown that the metabolism of docetaxel can change with the concomitant administration of drugs that induce or inhibit the activity of enzymes of the cytochrome P450-3A system, as well as metabolized with their participation (this may lead to competitive inhibition enzyme). Therefore, with the concomitant administration of drugs such as cyclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin, caution is necessary, given the possibility of significant interactions.Docetaxel binds well to blood plasma proteins (> 95%). Although no formal studies have been conducted on the in vivo interaction of docetaxel with other drugs, in vitro studies have shown that substances with a high degree of binding to proteins (such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylates, sulfamethoxazole and sodium valproate) do not affect on the connection of docetaxel with blood plasma proteins. Dexamethasone also does not affect protein binding of docetaxel.Docetaxel does not affect the binding of digitoxin to blood plasma proteins.
The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide do not change with the simultaneous administration of these drugs. There are limited data from a single uncontrolled clinical study showing an interaction between docetaxel and carboplatin. In combination therapy with docetaxel, carboplatin clearance was approximately 50% higher than previously obtained values ​​with carboplatin monotherapy.The pharmacokinetics of docetaxel in the presence of prednisone was studied in patients with metastatic prostate cancer. Docetaxel is metabolized with the participation of the isoenzyme CYP3A4, and prednisone is known to be an inducer of CYP3A4. However, no statistically significant effect of prednisone on the pharmacokinetics of docetaxel was found.
Docetaxel should be used with caution in patients concurrently receiving potent inhibitors of the CYP3A4 isoenzyme, in particular protease inhibitors (eg ritonavir), azole antifungals (eg ketoconazole or itraconazole).An interaction study has shown that with the combined use of ketoconazole, the clearance of docetaxel decreases by half, probably due to the fact that docetaxel is metabolized with the participation of the CYP3A4 isoenzyme (this is the main or only metabolic pathway). Therefore, tolerance to docetaxel may be impaired even at lower doses.

Special instructions :

For breast cancer and non-small cell lung cancer, oral premedication with corticosteroids (in the absence of contraindications), for example, dexamethasone at a dose of 16 mg / day (8 mg 2 times a day) for 3 days, starting 1 the day before docetaxel administration, can reduce the frequency and severity of fluid retention in the body, as well as the severity of hypersensitivity reactions.Patients with prostate cancer are recommended to undergo oral premedication with dexamethasone at a dose of 8 mg 12 hours, 3 hours and 1 hour before docetaxel administration.
Elderly age
There are no data on combination therapy with docetaxel, doxorubicin and cyclophosphamide in patients over the age of 70 years.
Among the 333 prostate cancer patients who received docetaxel every 3 weeks during the clinical study, 209 were 65 years of age or older and 68 were over 75 years of age.The frequency of development of changes in the nails in patients over the age of 65 was more than 10% higher than the corresponding indicators in younger patients. The incidence of treatment-related fever, diarrhea, anorexia, and peripheral edema in patients over the age of 75 was more than 10% higher than in patients under the age of 65.
Among 300 patients with gastric cancer (221 patients in a phase III clinical trial and 79 patients in a phase II study) who received docetaxel in combination with cisplatin and 5-fluorouracil, 74 were 65 years of age or older, and 4 were older than 75 years.The incidence of serious adverse reactions was higher among older patients. The incidence of side effects (of all severity) such as lethargy, stomatitis, neutropenic infections in patients over the age of 65 was more than 10% higher than in younger patients. Elderly patients receiving combination therapy with docetaxel, cisplatin, and 5 fluorouracil should be closely monitored.
Special warnings
Docetaxel Ebeve contains 27% (by weight) ethanol 96% (alcohol), i.e.That is, the average dose (160 mg of docetaxel) contains 4100 mg of alcohol, which is equivalent to less than 100 ml of beer.
This should be taken into account when prescribing the drug to persons who are contraindicated to drink alcohol – alcoholic patients, pregnant or breastfeeding women, children, high-risk patients, in particular, with liver disease or neurological diseases (for example, epilepsy).
The amount of ethanol in this medicine may alter the effect of other medicines.Interaction with other medicinal products and
other types of interaction
In vitro studies have shown that the metabolism of docetaxel can change with the concomitant administration of drugs that induce or inhibit the activity of enzymes of the cytochrome P450-3A system, as well as metabolized with their participation (in this case, competitive inhibition of the enzyme can occur). Therefore, with the concomitant administration of drugs such as cyclosporine, terfenadine, ketoconazole, erythromycin and troleandomycin, caution is necessary, given the possibility of significant interactions.Docetaxel binds well to blood plasma proteins (> 95%). Although no formal studies have been conducted on the in vivo interaction of docetaxel with other drugs, in vitro studies have shown that substances with a high degree of binding to proteins (such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylates, sulfamethoxazole and sodium valproate) do not affect on the connection of docetaxel with blood plasma proteins. Dexamethasone also does not affect protein binding of docetaxel.Docetaxel does not affect the binding of digitoxin to blood plasma proteins.
The pharmacokinetics of docetaxel, doxorubicin and cyclophosphamide do not change with the simultaneous administration of these drugs. There are limited data from a single uncontrolled clinical study showing an interaction between docetaxel and carboplatin. In combination therapy with docetaxel, carboplatin clearance was approximately 50% higher than previously obtained values ​​with carboplatin monotherapy.The pharmacokinetics of docetaxel in the presence of prednisone was studied in patients with metastatic prostate cancer. Docetaxel is metabolized with the participation of the isoenzyme CYP3A4, and prednisone is known to be an inducer of CYP3A4. However, no statistically significant effect of prednisone on the pharmacokinetics of docetaxel was found.
Docetaxel should be used with caution in patients concurrently receiving potent inhibitors of the CYP3A4 isoenzyme, in particular protease inhibitors (eg ritonavir), azole antifungals (eg ketoconazole or itraconazole).An interaction study has shown that with the combined use of ketoconazole, the clearance of docetaxel decreases by half, probably due to the fact that docetaxel is metabolized with the participation of the CYP3A4 isoenzyme (this is the main or only metabolic pathway). Therefore, tolerance to docetaxel may be impaired even at lower doses. There is no information on the use of docetaxel during pregnancy. Docetaxel has been shown to have embryotoxic and fetotoxic effects in rabbits and rats, and also to reduce fertility in rats.Like other cytotoxic drugs, docetaxel can cause fetal harm when used during pregnancy, so docetaxel should not be given to pregnant women.
Patients of childbearing age receiving docetaxel should be advised to prevent conception, and in case of pregnancy, immediately notify the attending physician.
Docetaxel is a lipophilic substance, but it is not known whether it is excreted in breast milk. Due to the possible development of unwanted adverse reactions in infants, breastfeeding should be discontinued during treatment with docetaxel.Influence on the ability to drive vehicles and other mechanisms
Docetaxel Ebeve contains 27% (by weight) ethanol 96% (alcohol), i.e. the average dose (160 mg of docetaxel) contains 4100 mg of alcohol, which is equivalent to less than 100 ml of beer.
The amount of ethanol in this medicinal product may adversely affect the ability to drive vehicles and operate other mechanisms.

Overdose :

Only a few cases of docetaxel overdose have been reported.The specific antidote for docetaxel is unknown. In case of an overdose, the patient is monitored in a specialized department and the vital functions of the body are closely monitored. In case of an overdose, an increase in adverse reactions is possible. The likely major complications of docetaxel overdose are bone marrow suppression, peripheral neurotoxicity, and mucosal inflammation. After identifying an overdose, the patient should be prescribed G-CSF as soon as possible. Other symptomatic measures can be taken if necessary.

Storage conditions :

In original packaging:
Store at a temperature not exceeding 25 ° C.
Do not refrigerate or freeze.
Store in original packaging and protected from light.
Storage conditions for infusion solutions are given in section 6.3.
Container
A vial made of hydrolytic class I clear glass, sealed with a fluoropolymer-coated halobutyl rubber stopper and an aluminum crimp cap with or without ONCO-SAFE protective plastic cap.Packaged:
1 bottle of 20 mg / 2 ml
1 bottle of 80 mg / 8 ml
1 bottle of 160 mg / 16 ml.

Before use, it is necessary to check for mechanical impurities and discoloration. Vials with sediment must be disposed of.
Preparation of solutions for infusion
Before use, the concentrate for solution for infusion must be diluted with 5% glucose solution or 0.9% sodium chloride solution.
The solution for infusion should be prepared no earlier than 4 hours before use.The required amount of the drug is taken directly from the bottle. More than one bottle may be required to obtain the dose required for the patient.
Based on the dose required for the patient (expressed in mg) and the concentration of the drug (10 mg of docetaxel in 1 ml), the required volume of the drug is calculated and taken from the bottle (s) using a graduated syringe equipped with a needle, subject to the rules of asepsis. For example, a 140 mg dose of docetaxel will require 14 ml of concentrate for infusion solution.The required volume of the drug is injected into an infusion bag or vial containing 250 ml of 5% glucose solution or 0.9% sodium chloride solution. For doses above 200 mg of docetaxel, a larger volume of carrier solutions should be used so that the concentration of docetaxel does not exceed 0.74 mg / ml.
The contents of the infusion bag or bottle are mixed by rocking them.
The resulting infusion solution should be used within 4 hours. It should be administered aseptically by a one-hour intravenous infusion at room temperature and normal lighting.From a microbiological point of view, the infusion solution should be administered
immediately after cooking.
pH and osmolarity of infusion solutions
Solution for infusion with a concentration of 0.3 mg / ml, prepared by diluting with 5% glucose solution: pH ≈ 3.6; osmolarity 517 mOsm / kg.
Solution for infusion with a concentration of 0.74 mg / ml, prepared by diluting with 0.9% sodium chloride solution: pH ≈ 3.3-3.6; osmolarity 849 mOsm / kg.

Shelf life :

In original packaging: 24 months.After dilution: solutions for infusion with a concentration of docetaxel (0.30 mg / ml and 0.74 mg / ml), prepared by diluting the drug with 5% glucose solution or 0.9% sodium chloride solution, are physically and chemically stable for 4 hours if stored at a temperature of 2-8 ° C in a dark place or at room temperature up to 25 ° C in a place not protected from light.
From a microbiological point of view, the infusion solution should be administered immediately after preparation.If the solution is not used immediately, the user should monitor the duration and storage conditions.

Manufacturer :

Sandoz Pharmaceuticals d.d., Slovenia Produced by: Ebewe Pharma Ges.m.b.H. Nfg.KG, Austria

ATX Code:

L01CD02

instructions, use, analogues of the drug, composition, indications, contraindications, side effects in the reference book of medicines from UNIAN

Docetaxel use

Docetaxel – composition and release form of the drug

Docetaxel: how to take the drug

Docetaxel – contraindications, side effects

Docetaxel’s analogs

Docetaxel is an antineoplastic drug, the mechanism of action of which is based on promoting the union of tubulin into stable microtubules and inhibiting their breakdown, which leads to a significant decrease in the level of free tubulin.Binding of docetaxel to microtubules does not change the number of protofilaments.

Use of Docetaxel

Breast cancer. Docetaxel in combination with doxorubicin and cyclophosphamide is intended for the adjuvant therapy of patients with:

– operable breast cancer with lymph node involvement;

– operable breast cancer without affecting the lymph nodes.

Patients with resectable breast cancer without lymph node involvement should be treated with adjuvant therapy if patients are to be treated according to internationally accepted criteria for primary treatment of early stages of breast cancer.

Docetaxel – composition and release form of the drug

Active ingredient: docetaxel;

1 ml of concentrate for solution for infusion contains 20 mg of docetaxel;

excipients: anhydrous citric acid, anhydrous ethanol, polysorbate 80.

Dosage form – concentrate for solution for infusion.

Basic physical and chemical properties: transparent solution of light yellow color.

Docetaxel: how to take the drug

Recommended doses .In the treatment of breast cancer, non-small cell lung cancer, stomach cancer, and head and neck cancer, premedication with oral corticosteroids such as dexamethasone 16 mg daily (eg 8 mg twice daily) for 3 days may be used (if not contraindicated); the first dose is taken 1 day before the first administration of docetaxel.

Docetaxel – contraindications, side effects

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.Baseline neutrophil count <1500 cells / mm3. Severe liver dysfunction.

Contraindications for the use of other drugs that are prescribed in combination with docetaxel should also be considered.

Side effects.

Immune system disorders. Hypersensitivity reactions generally developed within minutes of starting docetaxel infusion and ranged from mild to moderate in severity.The most commonly reported symptoms were skin redness, rash (with or without itchy skin), chest tightness, back pain, shortness of breath, fever, or chills. Severe adverse reactions were manifested in the form of arterial hypotension and / or bronchospasm or generalized rash / erythema.

Disorders from the nervous system. The development of severe peripheral neurotoxic reactions requires a dose reduction. Mild to moderate neurosensory responses included paresthesia, dysesthesia, or pain, including a burning sensation.Neuromotor reactions were manifested by general weakness.

Docetaxel analogs

  • Docetaxel
  • Taxotere
  • Docetaxel-Vista
  • Docetaxel-Teva

Source: State Register of Medicines of Ukraine. The instructions are published with abbreviations for information only. Before use, consult your doctor and read the instructions carefully. Self-medication can be harmful to your health.

instructions for use, analogs, articles »Directory of drugs

From the side of hematopoiesis: most often – reversible neutropenia, incl. with fever, the addition of infections, the development of sepsis and pneumonia; thrombocytopenia (including bleeding) and anemia.
Allergic reactions: hot flashes, skin rash, itching, chest tightness, back pain, shortness of breath, drug fever or chills, decreased blood pressure, bronchospasm, generalized rash / erythema, Lyell’s syndrome, Stevens-Johnson syndrome.
From the skin of the appendages of the skin: alopecia, skin reactions (including rash accompanied by itching or limited erythema of the skin of the extremities, including severe syndrome of damage to the palms and feet, with edema and subsequent desquamation, as well as hands, face and chest) , hypo- or hyperpigmentation of nails, onycholysis.
From the digestive system: nausea, vomiting, diarrhea, anorexia, constipation, stomatitis, taste disturbances, esophagitis, gastralgia, colitis (including ischemic), enterocolitis, gastrointestinal perforation, rarely – gastrointestinal bleeding, intestinal obstruction; increased activity of ACT, ALT, ALP, hyperbilirubinemia, hepatitis (incl.including fatalities in patients with a history of liver disease).
From the nervous system: peripheral neuropathy (paresthesia, hyperesthesia, dysesthesia or pain, including burning), muscle weakness, convulsions, loss of consciousness.
From the CVS: arrhythmia (sinus tachycardia, atrial fibrillation), heart failure, increase or decrease in blood pressure, venous thromboembolism, myocardial infarction.
Respiratory system: shortness of breath, pulmonary edema, acute respiratory distress syndrome, interstitial pneumonia, pulmonary fibrosis and increased response to radiation.
From the musculoskeletal system: arthralgia, myalgia, muscle weakness.
From the senses: lacrimation, incl. in combination with conjunctivitis, transient visual disturbances (flashes of light, scotoma), occlusion of the lacrimal canal (excessive lacrimation).
Local reactions: hyperpigmentation, inflammation, hyperemia, dry skin, phlebitis, hemorrhage, vein edema.
Other: asthenia, generalized or local pain, incl. in the chest (not associated with diseases of the heart and lungs), peripheral edema, pleural and pericardial effusion, ascites, weight gain, dehydration.
Overdose. Symptoms: deep myelosuppression, peripheral neurotoxic effects, inflammation of the mucous membranes.
Treatment: with persisting severe neutropenia and neutropenia with fever, colony-stimulating factors are indicated.

Side effects of therapy

How to cope?

– In order to detect neutropenia, anemia or thrombocytopenia during therapy, a clinical blood test is performed. After receiving the test results, the doctor can adjust the treatment and explain how to avoid infection.

– Before and during therapy, the patient is assigned to check the condition of the liver and kidneys. Drinking plenty of fluids is prescribed to avoid kidney damage.

– Side effects affecting the gastrointestinal tract (nausea, vomiting, diarrhea, changes in taste) can lead to loss of appetite and anorexia. A doctor will help prevent or eliminate these side effects.

– To eliminate a side effect such as peripheral neuropathy, you must inform your doctor about any of its manifestations (tingling or numbness of the hands or feet).

– Tell your doctor right away about any change in hearing or tinnitus. Most often, hearing changes are temporary.

– For timely correction, it is necessary to inform the doctor about any skin reactions, fluid retention / edema. It is also necessary to report any changes in the nail structure, arthralgia and myalgia so that the doctor can find a way to eliminate these side effects.

– Alopecia (baldness) is a reason for the disorder of many patients.Your doctor will tell you how to deal with this side effect (sometimes a cooling cap can be used to slow hair loss)

– To prevent stomatitis / inflammation of the soft tissues of the mouth, it is necessary to maintain careful oral hygiene using steroid rinses and toothpaste for sensitive teeth. Steroid toothpaste can be used to treat ulcers.