Paclitaxel (Taxol®): A new natural product with major anticancer activity

Abstract

Paclitaxel, the first of a new class of microtubule-stabilizing anti-tumor agents, has been hailed as the most significant chemotherapy advance in 15 years. Early clinical results showed response rates of 24%-30% in platinum refractory ovarian cancer at doses ranging from 110-250 mg/m(2) repeated every three to four weeks. The dose limiting toxicity is neutropenia which is characteristically profound, but brief. Severe hypersensitivity reactions which occurred in the phase I studies can be prevented by the use of anti-allergic pre-medication. From a slow start constrained by drug availability, the clinical development of paclitaxel has accelerated dramatically as the issue of product supply has been solved. Substantial activity has been reported in advanced breast cancer (56% RR in pre-treated patients; 62% RR in patients untreated for advanced disease) and non-small cell lung cancer (NSCLC) (20%-30% RR in advanced stage IIIb/IV patients). Significant activity has been reported also in melanoma, small cell lung cancer (SCLC), bladder cancer, squamous cell carcinoma of the head and neck, and of the esophagus, cervical and endometrial cancer, as well as lymphomas. Combination chemotherapy studies have shown high activity in a variety of tumor types. Superiority over standard therapy has been demonstrated in ovarian and lung cancer in phase III randomized studies. Paclitaxel's novel mechanism of action and relative lack of clinical cross-resistance with other agents suggest a role in the combination therapy of early stage disease.