Single-agent paclitaxel for the treatment of breast cancer: an overview.

Initial trials using a 24-hour intravenous infusion of 250 mg/m2 paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of breast cancer yielded objective regression in 56% to 62% of patients with no or only one prior chemotherapy regimen. Tolerance to single-agent paclitaxel seemed acceptable, but after multiple cycles, peripheral neuropathy developed in a significant fraction of patients. Lower doses and, more recently, the 3-hour infusion schedule still produced objective responses, albeit lower, in the range of 20% to 35%. It became apparent that toxicity was dose and schedule dependent, and likely there was a dose-response correlation. A 96-hour infusion schedule yielded a maximum tolerated dose of 140 mg/m2, and no hypersensitivity reactions despite omission of the standard triple-drug premedication. More recently, a 1-hour infusion schedule (plus standard triple-drug premedication) was well tolerated, with activity in both lung and breast cancer similar to that observed after a 3-hour infusion treatment. Paclitaxel retained therapeutic activity, even among patients with anthracycline-refractory breast cancer, in clinical trials using the 3-, 24-, and 96-hour infusion of paclitaxel. Current ongoing trials will explore the range of paclitaxel activity of various doses and by alternative schedules, both as second-line therapy and in the adjuvant and neoadjuvant setting.