Docetaxel: Effects, Uses & Risks

The cytostatic drug docetaxel belongs to the group of taxanes. It is used for the therapy of various cancers.

What is docetaxel?

Docetaxel is a cytostatic drug that belongs to the taxane group of drugs. The drug is produced by the French pharmaceutical company Sanofi. Docetaxel is a structural derivative of the cytostatic drug paclitaxel. The drug is produced semisynthetically from precursors found in the European yew tree (Taxus baccata). While the first taxane paclitaxel was obtained from the Pacific yew tree or its bark, docetaxel succeeded in isolating the substance 10-deacetyl-baccatin-III from the European yew tree. The esterification is followed by the formation of docetaxel. The advantage is that the European yew is more readily available than the very slow-growing Pacific yew. The approval of docetaxel took place in Europe in the 1990s. As an infusion preparation, it is on the market in Germany under the trade name Taxere.

Pharmacologic action

The action of docetaxel is based on the inhibition of tumor growth. Before a cancer cell divides and multiplies, cleavage of the cell nucleus and separation of the two halves is required. For this purpose, small protein filaments called microtubules are formed by the cell. The filaments have the property of attaching themselves to the inner wall of the cell. The same is true for the half of the nucleus that faces the inner direction. Pulling the halves of the nucleus apart takes place by shortening the protein filaments. In this way, the cell walls of the daughter cells can be formed in the interstitial space. Docetaxel exerts its positive effect by interfering with the process of cell division. Thus, its influence leads to an excessive formation of microtubules, which in turn slows down their degradation for reuse. As a result, the cell no longer receives sufficient filaments, which serve as building material for cell division. In the further course, cell proliferation stops. This process has a more detrimental effect on cancer cells than on healthy body cells, as they divide more rapidly. Docetaxel also has the property of not only inhibiting but also killing the cancer cells. The reason for this is that the microtubules are also important for transporting important substances during cell division. Docetaxel is metabolized in the liver.

Medical application and use

Docetaxel is used for the treatment of various cancers. It can be administered as a monopreparation or combined with other cytostatic drugs. This is done, for example, in the treatment of breast cancer, in which the patient receives cyclophosphamide and doxorubicin in addition to docetaxel. This is particularly the case when the cancer originates in nodes that can be operated on. Together with doxorubicin, docetaxel is also used to treat breast cancer that has metastasized. In this case, however, no other chemotherapy may have been administered beforehand. As a mono-preparation, docetaxel is only used if the tumor has progressed locally or if daughter tumors have formed. It is also used when chemotherapy with alkylating cytostatic agents or anthracyclines has been unsuccessful. Occasionally, docetaxel is also administered together with capecitabine in such cases. Another indication is lung cancer. The cytostatic drug is used singly for locally advancing non-small cell lung cancers or the formation of metastases. If this form of cancer cannot be treated surgically, it is not uncommon for it to be combined with cisplatin. In the context of prostate cancer, treatment with docetaxel takes place when hormone therapy is unsuccessful and metastases have developed. In this case, the cytostatic drug is used together with prednisolone or prednisone. In the case of adenocarcinoma of the stomach, docetaxel is part of a combination treatment with 5-fluorouracil and cisplatin. This treatment takes place in the presence of daughter tumors, provided that no chemotherapy has been performed in advance. An additional area of application for docetaxel is cancers in the head and neck region. In this case, squamous cell carcinomas are treated.

Risks and side effects

Patients almost always suffer side effects from treatment with docetaxel.These primarily include neuropathies as well as moderately severe neutropenias in which a drop in neutrophil granulocytes occurs. However, dangerous febrile neutropenia accompanied by fever is rare. The blood formation disorders are seen in up to 95 percent of all patients, but can be mitigated with appropriate medication. Other frequent undesirable side effects include fever, disturbances in the sense of taste, sensory disturbances in the limbs, inflammation of the oral mucosa, breathing problems, disturbances in movement control, hair loss, diarrhea, nausea, vomiting, muscle pain, changes in the nails, skin reactions, infections such as pneumonia or blood poisoning, fluid retention, pain, feelings of weakness, and loss of appetite. Furthermore, patients may experience abdominal pain, constipation, low blood pressure, a lack of platelets, a blood-bilirubin increase, joint pain and chest pain. Occasionally, patients also suffer from inflammation of the esophagus. In the worst case, even heart failure is possible. The extent of side effects also depends on the amount of docetaxel dose administered and the use of other cytostatic drugs. If there is hypersensitivity to docetaxel, the chemotherapeutic agent must not be administered. The same applies in the case of a pronounced liver dysfunction and an abnormal blood count. In the case of a watery belly (ascites), consistent monitoring by the physician is required. Docetaxel must not be administered during pregnancy and breastfeeding. Consistent contraceptive measures are recommended if therapy is given.