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.
Hortobagyi
G N
GN
Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas, USA.
Holmes
F A
FA
D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D004334:Drug Administration Schedule; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic
D000972:Antineoplastic Agents, Phytogenic; D016179:Granulocyte Colony-Stimulating Factor; D017239:Paclitaxel