Pharmacology of Paclitaxel and Docetaxel

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Paclitaxel and docetaxel are taxoid drugs extracted from the bark of the Pacific yew and the needles of the English yew, respectively. Both work against cancer by interfering with mitosis, but they each do it a little differently.

Paclitaxel, which is sold as Taxol by Bristol-Myers Squibb, binds to microtubules and inhibits their depolymerization (molecular disassembly) into tubulin. This means that paclitaxel blocks a cell's ability to break down the mitotic spindle during mitosis (cell division). With the spindle still in place the cell can't divide into daughter cells (this is in contrast to drugs like colchicine and the Vinca alkaloids, which block mitosis by keeping the spindle from being formed in the first place).

Paclitaxel is given intravenously (it irritates skin and mucous membranes on contact), and is most effective against ovarian carcinomas and advanced breast carcinomas. Slightly less than half of the patients receiving paclitaxel during clinical trials developed an allergic reaction to it, which resulted in problems ranging from rashes or a mild drop in blood pressure to major breathing problems, hives and/or fluid buildup around the heart. To counteract this risk of developing a reaction, patients are pre-treated with corticosteroids and diphenhydramine (an antihistamine) before they undergo paclitaxel therapy. Other adverse reactions include abnormally low neutrophil (which can leave the patient vulnerable to infection) and abnormally low platelet counts, which can cause hard-to-control bleeding. Anemia and bone and muscle pain were also common side effects.

[image of docetaxel molecule]

Docetaxel has been trademarked as Taxotere by Rhone-Poulenc Rorer as an investigational drug. Like paclitaxel, it prevents the mitotic spindle from being broken down by stabilizing the microtubule bundles, but clinical trials indicate it's about twice as effective as paclitaxel in doing so.

Docetaxel, which is also given intravenously, is being tested on carcinomas of the bladder, cervix, lung, and ovaries; on malignant melanoma; and on non-Hodgkin's lymphoma.

Thus far, side effects of docetaxel therapy include allergic reactions, skin rashes, fluid buildup (edema), abnormally low neutrophil counts, and peripheral nervous system disorders.

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Reference:

1995 Physician's Desk Reference ©. Montvale, NJ, Medical Economics Data Production Company.

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