The taxoids: same roots, different drugs.

The discovery and development of the taxoid class of antitumor compounds, most notably paclitaxel, originally extracted from the Pacific yew, and its semisynthetic analog docetaxel, represent significant advances in the treatment of patients with a variety of malignancies. Although paclitaxel and docetaxel have a similar chemical root, extensive research and clinical experience indicate that important biological and clinical differences exist between the two compounds. Although the mechanism by which they disrupt mitosis and cell replication is novel and unique to this class of compounds, there are small but important differences in the formation of the stable, nonfunctional microtubule bundles and in the affinity of the two compounds for binding sites. These differences may explain the lack of complete cross-resistance observed between docetaxel and paclitaxel in preclinical and clinical studies. The two taxoids also exhibit slightly different toxicity and clinical efficacy profiles. Docetaxel-induced adverse events have been shown to occur most frequently in patients with impaired liver function, and a reduction in dosage in patients with raised levels of transaminases and alkaline phosphatase is recommended to improve the tolerability of the drug in these patients. The incidence and severity of problematic adverse effects such as hypersensitivity, skin reactions, and a cumulative fluid retention syndrome are minimized with the routine administration of a 3- to 5-day corticosteroid-based premedication regimen with each docetaxel infusion. The results of ongoing studies of taxoid-based monotherapies and combination regimens will further optimize the benefits achievable with these drugs, and new preclinical findings also may lead to new clinical uses for these and future drugs of the taxoid class.