Taxotere

About 3 million women in the U.S. are living with breast cancer, according to Breastcancer.org. Over 300,000 new cases are expected each year.

Oncologists use Taxotere (known generically as docetaxel) in a vast majority of breast cancer patients.

Up to 75 percent of these women will receive the chemotherapy drug for treatment.

In studies, Taxotere performed better than other drugs in extending survival of breast cancer patients. However, the drug may also have a distressing side effect for breast cancer survivors: permanent hair loss, also called alopecia. In women, this side effect is particularly disfiguring.

In addition to hair loss, Taxotere has also been linked to toxic deaths and other potentially life-threatening side effects. In 2014, the FDA also issued a safety communication about the potential for patients to experience intoxication during or following the administration of the drug due to alcohol in the active ingredient, docetaxel.

Taxotere is used to treat various types of cancer, including breast cancer, non-small cell lung cancer (NSCLC), prostate cancer, gastric adenocarcinoma (stomach cancer), and head and neck cancer. Its earliest FDA-approval was for the treatment of NSCLC in 1999. Prostate and breast cancer approvals followed in 2004, with stomach, head and neck cancers obtaining approval for treatment with Taxotere in 2006.

Cancer is when the body’s cells divide without stopping and spread into surrounding tissues, according to the National Institutes of Health (NIH). This can occur almost anywhere in the human body.

Under healthy conditions, the body’s cells grow and divide to form new cells as needed. The old or damaged cells then die off, so the new cells can take their place. With cancer, this process breaks down. Old or damaged cells remain alive when they should otherwise die. New cells form when they’re not needed. As these extra cells begin to divide, they can form growths called tumors.

Cancerous tumors are called malignant, meaning they can spread to nearby tissues. Some cancer cells can also break off and travel through the blood or the lymphatic system, forming new tumors distant from the original one.

In patients with breast cancer, Taxotere is used to treat those cases that are locally advanced or metastatic after failure of prior chemotherapy. Taxotere is also used as an adjuvant (a substance that aids another or modifies the effect of other agents) treatment in patients with operable node-positive breast cancer (meaning it has been found in the lymph nodes in the armpit area) in combination with doxorubicin and cyclophosphamide.

Like other types of chemotherapy drugs, Taxotere works by stopping cells from dividing and multiplying. Normal, healthy cells stop dividing when they are around similar cells. Cancer cells, however, are damaged. They no longer have the ability to stop dividing. This is how cancer continues to spread. Chemotherapy drugs like Taxotere attack the cancer cells’ DNA or RNA so the tumor can no longer copy itself and spread.

Along with another chemo drug called Paclitaxel, Taxotere belongs to a specific class of drug called a taxane. Taxanes are made from plant alkaloids. Specifically, Taxotere is made from the bark of the Pacific Yew tree. It works by inhibiting microtubules within cancer cells. Microtubules are necessary for cell division and replication. When the cell can no longer divide or replicate, it dies.

While chemotherapy is known to cause hair loss, most cases resolve in three to six months after the treatment is finished, and the patient’s hair completely regrows. Hair loss following chemotherapy is one of the most distressing side effects of treatment. Studies show it has a direct impact on quality of life. Permanent hair loss can be devastating.

Some studies now show that Taxotere can cause permanent, irreversible alopecia. All body hair is affected, including eyebrows, eyelashes and pubic hair.

The GEICAM 9805 funded by Sanofi, revealed that about 9.2 percent of patients suffered hair loss that lasted 10 years or longer, according to data presented in the lawsuit of Ami Dodson.

Another study conducted by Dr. Scot Sedlacek of the Rocky Mountain Cancer Centers showed that Taxotere could cause 6 percent of women to suffer permanent alopecia.

A 2012 study published in the Annals of Oncology followed 20 women on Taxotere. Nineteen had permanent hair loss, including eyebrow and eyelash loss. One patient treated for reoccurring breast cancer previously underwent chemotherapy with different drugs and had complete hair regrowth. After she received Taxotere, she suffered permanent hair loss.

Taxotere has a number of other side effects associated with its use. Many of these are reversible, though in some cases these complications can result in death.

*Occurs in 10 to 29 percent of patients

Toxic death occurred in about 2 percent (19 out of 965) of metastatic breast cancer patients using Taxotere, according to the medication insert. The deaths occurred at a dose of 100 mg/m2. Death occurred in 11.5 percent (7 out of 61) of patients with other tumor types with abnormal liver function.

Taxotere includes a black box warning (or boxed warning), the FDA’s most serious type of warning, for several conditions that can result in serious injury or death for patients given the chemotherapy drug. Patients experiencing any of these serious side effects resulting from treatment with Taxotere, may require dose adjustments or may need to discontinue the drug.

On June 20, 2014, the FDA issued a safety announcement warning that the drug contains ethanol (also known as alcohol), and therefore, may cause patients to experience intoxication or its effects, meaning they may feel drunk during and after treatment. The federal agency required a revision of drug labels for all docetaxel-containing drugs to reflect this warning.

The FDA further advised that health care professionals should consider the alcohol content of docetaxel when prescribing and administering the chemotherapy drug to patients, especially for those individuals for whom alcohol intake should be avoided or minimized and when used along with other medications. The agency advised that the alcohol content in a single dose of docetaxel may affect the central nervous system and therefore, a docetaxel formulation with the lowest possible alcohol content should be used in patients who experience adverse reactions.

Administering the drug at a slower infusion rate was also found to be helpful in resolving symptoms of alcohol intoxication in some patients, according to the FDA. Data reviewed from the FDA Adverse Event Reporting System (FAERS) database, along with medical literature identifying three cases of alcohol intoxication associated with docetaxel, found that one patient did not experience any symptoms of intoxication during drug administration, but did experience symptoms within 24 hours following treatment.

There is no oral pill form of Taxotere. The drug is given intravenously. One day before therapy starts, patients take corticosteroid pills to reduce fluid retention and allergic reactions to the drug. This continues for three days. Depending on a patient’s height, weight, type of cancer and general health, the doctor will determine the dose and schedule of chemotherapy.

Doctors will first try to reduce the dose, but if the symptoms worsen or continue at lower doses, the treatment should be discontinued.

In case of a possible overdose, patients need to be monitored and given granulocyte-colony stimulating factor (G-CSF). G-CSF is a protein that causes the bone marrow to produce stem cells and white blood cells and release them into the bloodstream. These cells will help prevent infection and fever.

According to the medication insert, two overdoses were reported in patients. Both patients experienced asthma, skin reactions and tingling or prickling of the skin; but they both recovered following appropriate treatment.

When Taxotere is used along with cytochrome P450 3A4 (CYP3A4) inducers, inhibitors or substrates it may alter the metabolism of the drug’s active ingredient docetaxel (a CYP3A4 substrate). Cytochrome P450 3A4 is an important enzyme in the body, mainly occurring in the liver and the intestine. It metabolizes approximately 50 percent of all marketed drugs in the body, according to the National Institutes of Health (NIH).

In pregnant women, Taxotere can cause harm to the fetus, as shown in animal studies. The drug label advises that women taking Taxotere should avoid becoming pregnant. It is not known if Taxotere is excreted into a nursing mother’s milk, but there is a potential for serious adverse reactions to nursing infants if exposure occurs.

When Taxotere is administered to children, the alcohol content of docetaxel should be considered with dosing. In general, dosing for an elderly patient should be cautious, reflecting the greater frequency of decreased liver, kidney and cardiac function, and the presence of other diseases and/or drug treatments, in this specific population.

Patients with impaired liver function exhibiting unusually high bilirubin levels should not be given Taxotere. Bilirubin is a brownish-yellow substance found in bile that is produced when old red blood cells are broken down in the liver. High levels of the substance can lead to jaundice, which often results in the yellowing of the skin and eyes. The alcohol content of Taxotere should be taken into account when administering the drug to patients with liver impairment.