Paclitaxel: a new antimitotic chemotherapeutic agent

Paclitaxel, a compound derived from the bark of the Pacific yew, Taxus brevifolia, is an antimitotic cytotoxic agent with a mechanism of action different from other antimitotics such as vincristine and vinblastine. Instead of causing disassembly of microtubules, paclitaxel forms extremely stable and nonfunctional microtubules, which causes inhibition of many cell functions and the interruption of the cell cycle. Procurement of paclitaxel has raised environmental concerns, leading researchers to explore a variety of approaches to obtain the drug: extraction from yew needles of a paclitaxel precursor that can be converted to paclitaxel, genetic manipulation of plants to increase yield, propagation of yew trees, semisynthesis, total chemical synthesis, and paclitaxel-producing fungus. Clinical trials involving paclitaxel have demonstrated antineoplastic effects in several classically refractory tumors: ovarian cancer, breast cancer, non-small-cell lung cancer, and head and neck tumors. Several toxic effects have been attributed to paclitaxel, including hypersensitivity reactions, cardiotoxicities, neutropenia, peripheral neuropathy, mucositis, gastrointestinal toxicities, alopecia, arthralgias, and myalgias. Clinical implications for these toxicities are addressed.