An overview of experience with TAXOL (paclitaxel) in the U.S.A

TAXOL (paclitaxel) is a unique new antineoplastic agent that has generated a considerable amount of scientific interest from many disciplines since it entered clinical trials in the early 1980s. There are a number of reasons for this interest. The natural biological source for this agent is the bark of the Pacific yew in the ancient forests of the northwestern U.S.A. The initial problems with supply of the agent and the desirability of a renewable source has stimulated the creativity of medicinal chemists and others interested in alternate sources of supply. The unique mechanism of action and the effect of TAXOL on microtubule structure and function continues to be the subject of intense investigative interest. Clinical investigators have had to contend with troublesome and potentially serious toxicities, which have threatened the development of TAXOL, but have been rewarded with a drug that appears to have broad antitumor activity against a number of advanced solid tumors in man. The purpose of this review is to provide an overview of the clinical experience with TAXOL, which has been developed in the U.S.A. over the last 10 years with more than 4,000 patients, and to outline what issues remain in the optimization of its use.