The group of taxanes includes the active ingredients paclitaxel, docetaxel, and cabazitaxel. Their action is due to the disruption of cell division (mitosis), which medicine uses to treat various cancers.
What are taxanes?
Taxanes form a group of agents that belong to the cytostatic drugs and are also known as taxoids. They are used in the treatment of various types of cancer, where they serve as chemotherapeutic agents. In this context, they can often be found in combinations with other active ingredients. The taxane that was first discovered was paclitaxel. In 1962, physicians extracted it for the first time from the bark of the Pacific yew tree and in subsequent studies established its effect on cancer cells. In 1993, paclitaxel received approval in Germany as a drug to treat ovarian cancer. Docetaxel, which was developed later, is a derivative of paclitaxel and is also a taxane. Its pharmaceutical production is based on a substance derived from the European yew tree, where it is found in the bark. Since the tree grows faster than the Pacific yew, this production offers practical advantages. Improved active ingredients in the form of second-generation taxanes have not yet been approved, but are under development.
Pharmacological action
The exact mechanism of action of taxanes may vary slightly depending on the agent. What they all have in common is that they inhibit the natural process of cell division. The process, known as mitosis, is as relevant to healthy cells as it is to cancer cells. In tumors, however, the increased formation of new cells leads to the development of the ulcer. During the first phase of mitosis, prophase, the centriole duplicates and one of each migrates to one pole of the cell. From there, the cell organelle forms the spindle fibers, which are composed of microtubules and form the spindle apparatus. In undisturbed mitosis, the spindle fibers attach to the chromosomes in metaphase and separate them centrally into two parts during anaphase, giving each of the two halves of the cell a chromatid. The spindle apparatus dissolves again in the final telophase and the cell finally divides. Taxanes interfere with mitosis by preventing the degradation of the spindle apparatus in telophase. For this reason, taxanes are also considered spindle poisons. The cell is subsequently no longer able to duplicate and the body initiates programmed cell death instead. This process is also known as apoptosis and leads to the destruction of the cell. Because tumor cells have a particularly high rate of division, the effect of taxanes hits them harder than healthy cells, most of which reproduce more slowly.
Medical application and use
Taxanes are used in cancer therapy. Because they represent a group of active substances, the indication for a taxane depends not only on the type of substance but also on the preparation of the particular drug. In addition, the use depends on individual factors and can only be decided on a case-by-case basis. Combinations with other cytostatics and drugs from other drug groups are also common in practice after careful coordination. Paclitaxel is used for bronchial carcinoma of the lung and breast carcinoma of the breast. Breast cancer represents the most common cancer in women. In addition, paclitaxel is used as part of chemotherapy for ovarian cancer in women or prostate cancer in men. In addition, medicine sometimes uses the taxane paclitaxel for drug-eluting stents. These are stents that are coated with a pharmacological substance and release their drug over several weeks. Cabazitaxel is indicated primarily for mHRPC. The abbreviation stands for “metastatic hormone refractory prostate cancer” and refers to a more severe course of the cancer in which spread of the tumor occurs. Cabazitaxel is used after prior treatment with docetaxel. Medicine uses it in combination with prednisone or prednisolone. Prednisone and prednisolone belong to the group of glucocorticoids and generally have an anti-allergic and anti-inflammatory effect. In addition to prostate carcinoma, ovarian, breast, gastric and non-small cell bronchial carcinoma are also possible reasons for using docetaxel.
Risks and side effects
Risks and side effects of taxanes differ depending on the specific agent and preparation. However, the substances have in common that they act primarily on cells that divide rapidly. Allergic and hypersensitive reactions are possible with all taxanes. The respective contraindications that apply to a given preparation must also be observed. In general, taxanes can affect blood cells and decrease the amount of platelets (thrombocytopenia), decrease the number of neutrophil granulocytes (neutropenia), or decrease hemoglobin concentration (anemia). Common side effects of the taxane paclitaxel include hair loss (alopecia) and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Neuropathy and muscle pain (myalgia) are other potential side effects. Docetaxel use is also associated with neuropathy. Liver dysfunction is also possible. Known side effects of cabazitaxel include a reduction in leukocytes (leukocytopenia) in addition to the aforementioned blood count abnormalities, which can also occur with the other two taxanes. Diarrhea, constipation, vomiting, lack of appetite, and taste disturbances may also manifest. Possible side effects of cabazitaxel also include cardiac arrhythmias, general aches and joint pain, fever, and fatigue.
