Taxol: A Novel Investigational Antimicrotubule Agent

Abstract

Microtubules are among the most strategic subcellular targets of anticancer chemotherapeutics. Despite this fact, new antimicrotubule agents that possess unique mechanisms of cytotoxic action and have broader antineoplastic spectra than the vinca alkaloids have not been introduced over the last several decades--until the recent development of taxol. Unlike classical antimicrotubule agents like colchicine and the vinca alkaloids, which induce depolymerization of microtubules, taxol induces tubulin polymerization and forms extremely stable and nonfunctional microtubules. Taxol has demonstrated broad activity in preclinical screening studies, and antineoplastic activity has been observed in several classically refractory tumors. These tumors include cisplatin-resistant ovarian carcinoma in phase II trials and malignant melanoma and non-small cell lung carcinoma in phase I studies. Taxol's structural complexity has hampered the development of feasible processes for synthesis, and its extreme scarcity has limited the use of a conventional, broad-scale screening approach for evaluation of clinical antitumor activity. However, taxol's unique mechanism of action, its spectrum of preclinical antitumor activity, and tumor responses in early clinical trials have generated renewed interest in pursuing its development.

Phase I study of temozolomide plus paclitaxel in patients with advanced malignant melanoma and associated in vitro investigations

“…It was discovered in the early sixties by the National Cancer Institute (Rowinsky and Donehower, 1995). Early clinical studies indicated activity against a number of tumours including ovarian, breast, lung and melanoma (Rowinsky et al, 1990;Einzig et al, 1991b;Ettinger, 1993;Martin, 1993). Paclitaxel was first approved by the FDA in 1992 to be used as a second-line treatment for ovarian carcinoma (Arbuck et al, 1993).…”

A phase II study of paclitaxel, weekly, 24-hour continuous infusion 5-fluorouracil, folinic acid and cisplatin in patients with advanced gastric cancer

“…Paclitaxel is an antimitotic agent with the unique cytotoxic mechanism of tubulin stabilization and polymerization, resulting in nonfunctional microtubules (Rowinsky et al, 1990). Paclitaxel exhibits an antitumour activity against various tumours including gastric cancer cell lines (Vanhoefer et al, 1995;Chang et al, 1996).…”

Paclitaxel combined with fractionated radiation in vitro: A study with vulvar squamous cell carcinoma cell lines

“…1 The mechanism of action of paclitaxel is based on promotion of microtubule assembly and the stabilization of these microtubules. This results in arrest in the G 2 /M phase of the cell cycle.…”