Paclitaxel

Paclitaxel (Taxol) is a highly complex, organic compound isolated from the bark of the Pacific yew tree. It binds to tubulin dimers and microtubulin filaments, promoting the assembly of filaments and preventing their depolymerization. This increase in the stability of microfilaments results in disruption of mitosis and cyto-toxicity and disrupts other normal microtubular functions, such as axonal transport in nerve fibers.

The major mechanism of resistance that has been identified for paclitaxel is transport out of tumor cells, which leads to decreased intracellular drug accumulation. This form of resistance is mediated by the mul-tidrug transporter P-glycoprotein.

Paclitaxel's large volume of distribution indicates significant tissue binding. The drug is extensively metabolized by the liver, and doses must be reduced in patients with abnormal liver function or with extensive liver metastases. Very little of the drug is excreted in the urine.

Paclitaxel is among the most active of all anticancer drugs, with significant efficacy against carcinomas of the breast, ovary, lung, head, and neck. It is combined with cisplatin in the therapy of ovarian and lung carcinomas and with doxorubicin in treating breast cancer.

Myelosuppression is the major side effect of pacli-taxel. Alopecia is common, as is reversible dose-related peripheral neuropathy. Most patients have mild numbness and tingling of the fingers and toes beginning a few days after treatment. Mild muscle and joint aching also may begin 2 or 3 days after initiation of therapy. Nausea is usually mild or absent. Severe hypersensitivity reactions may occur. Cardiovascular side effects, consisting of mild hypotension and bradycardia, have been noted in up to 25% of patients.

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