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Taxol, a substance obtained from the bark of Pacific yew , has
inhibited the growth of various types of cancer cells in experimental
tests [1,44]. Clinical trials indicate that taxol produces a definite
but limited activity against metastatic melanoma and some types of
leukemia . It may also be useful in treating ovarian cancer and in
inhibiting the growth of carcinosarcoma cells [11,44,38]. Taxol
inhibits the replication of Trypanosoma cruzi, a pathogenic protozoan
which causes Chagas disease , as well as the disease-causing
flagellate Trichomonas vaginalis .
Taxol, a diterpene alkaloid, has poor aqueous solubility and is formulated as a solution in 50% Cremophor EL and 50% dehydrated alcohol, USP (Adams et al., 1993). For medical use, it is administered intravenously by a 3 to 24 hour infusion three times per week (Guchelaar et al., 1994).
Taxol's mechanism of antitumor activity is unique because it promotes microtubule assembly and stabilizes the microtubules, thus preventing mitosis (Huizing et al., 1995). Taxol does this by reversibly and specifically binding to the B subunit of tubulin, forming microtubule polymers leading to growth arrest in the G2/M phase of the cell cycle (Gotaskie and Andreassi, 1994). This makes taxol unique in comparison to vincristine and vinblastine which cause microtubule disassembly (Gatzemeier et al., 1995). Additionally, recent evidence indicates that the microtubule system is essential to the release of various cytokines and modulation of cytokine release may play a major role in the drug's antitumor activity (Smith et al., 1995).
Due to taxol's antimitotic activity, it is a useful cytotoxic drug in treating several classic refractory tumors including head and neck cancer, small cell and non-small cell lung cancer and most notably breast and ovarian carcinomas. It may also slow the course of melanoma. Response rates to taxol treatment varies among cancers. Advanced drug refractory ovarian cancer responds at a 19-36% rate, previously treated metastatic breast cancer at 27-62%, and various lung cancers at 21-37%. Taxol has also been shown to produce complete tumor remission in some cases (Guchelaar et al., 1994).
In addition, taxol plus radiation treatment has an additive but not synergistic effect as shown in an experiment using a cervical carcinoma line (Minarik and Hall, 1994). Elderly patients aged more than 60 years did not differ with respect to administered dose intensity, number of cycles of therapy administered, or the occurrence of serious or mild toxicities (Bichner et al., 1993). Thus, elderly patients receiving taxol can be treated as aggressively as younger patients. Clinically, taxol treatment is a possible adjunct to radiation.