Taxotere Side Effects

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.

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.

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% of patients may experience potentially life-threatening reactions.

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

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.

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

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 (H2) receptor blocker before docetaxel.

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.

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.

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% 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% 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% 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% to 15% 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.

Studies have linked Taxotere to a type of eye problem called epiphora, a condition where the eyes produce excessive tears. Doctors attribute the condition to canalicular stenosis caused by Taxotere. Canalicular stenosis is a condition that causes narrowing or blockage of the tear ducts.

In some patients, epiphora was severe enough to adversely affect quality of life by preventing daily activities, such as reading, watching TV or driving.

The first reports of ephiphora as a Taxotere side effect appeared in the journal Ophthalmology in 2001, and more reports have found up to 50% of patients who have weekly Taxotere treatments reported epiphora. Symptoms don’t usually resolve after Taxotere treatment stops.

Symptoms of epiphora include excessive wetness in the eyes, excessive overflow of tears and blurred vision. In order to treat epiphora, doctors have to place silicone tubes in the eyes to help tears drain properly. In severe cases, doctors perform a dacryocystorhinostomy (DCR). DCR creates a new path for tears to drain.