Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxelin patients with metastatic or locally advanced breast cancer: National surgical adjuvant breast and bowel project protocol B-26

Purpose: Paclitaxel is an active drug for the treatment of breast cancer; h owever, the appropriate duration of administration is unknown. We assessed and compared the response rate, event-free survival, survival, and toxicity of paclitaxel 250 mg/m(2) delivered every 3 weeks as a 3-hour or 24-hour i nfusion. Patients and Methods: A total of 563 women with stage IV or IIIB breast can cer were randomized into one of two groups: 279 received 3-hour paclitaxel and 284 received 24-hour paclitaxel, Patients were stratified by age, stage of disease, and prior therapy. Results: A significantly higher rate of tumor response occurred in the firs t four cycles of therapy in patients who received the 24-hour infusion of p aclitaxel (51% v 41%, respectively; P = .025), Tumor response over all cycl es was also significantly higher in the group that received 24-hour infusio n (51% v 44%, respectively; P = .023), There were no significant difference s in event-free survival or survival between the two arms of the study (P = .9 and .8, respectively), No treatment by stage or by age interactions wer e observed. During the first four cycles of therapy, at least one episode o f greater than or equal to grade 3 toxicity (excluding nadir hematologic va lues, alopecia, and weight change) occurred in 45% of patients who received the 3-hour paclitaxel infusion and in 50% of those who received the 24-hou r paclitaxel infusion. Febrile neutropenia, greater than or equal to grade 3 infection, and greater than or equal to grade 3 stomatitis were less freq uent, and severe neurosensory toxicity was more frequent in those who recei ved the 3-hour paclitaxel infusion. Ten treatment-related deaths occurred i n the first tour cycles. Age, stage, and prior chemotherapy did not influen ce the effect of treatment. Conclusion: When administered as a continuous 24-hour infusion, high-dose p aclitaxel results in a higher tumor response rate-than when administered as a 3-hour infusion but does not significantly improve event-free survival o r survival, paclitaxel as a 24-hour infusion results in increased hematolog ic toxicity and decreased neurosensory toxicity. (C) 1999 by American Socie ty of Clinical Oncology.