Taxol: the first of the taxanes, an important new class of antitumor agents.
The taxanes represent the first class of antimicrotubule agents with a new mechanism of cytotoxic action since the introduction of the vinca alkaloids several decades ago. These compounds may prove to be the "anticancer drugs of the 1990s," just as the anthracyclines and the platinum compounds were the "anticancer drugs" of the 1970s and 1980s. Like the platinums, taxol, the prototypic taxane, has shown significant antineoplastic activity in patients with advanced ovarian cancer, with response rates ranging from 20% to 50%. Moreover, taxol has been shown to be useful in patients with platinum-resistant ovarian cancer. Although phase II screening is not yet complete, the results of phase II studies of taxol in advanced cancers of the ovary, breast (response rates, 56% to 62%), and lung (response rates, 21% to 24%) have rekindled interest in the microtubule as a prime strategic target for cancer therapy. After briefly reviewing the mechanisms of antineoplastic action and resistance and the results of preliminary clinical and pharmacological studies, this review will discuss several critical issues that will be addressed in future clinical trials, developmental directions, and drug supply. Although this review will focus primarily on taxol, the results of preliminary investigations with the semisynthetic taxane analog taxotere will also be discussed.
Division of Pharmacology and Experimental Therapeutics, Johns Hopkins Oncology Center, Baltimore, MD 21205.
E K
EK
Rowinsky
N
N
Onetto
R M
RM
Canetta
S G
SG
Arbuck
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005544:Forecasting; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology / Q000627:therapeutic use; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D015507:Drugs, Investigational; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel