Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in 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; however, 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 infusion. Patients and Methods: A total of 563 women with stage IV or IIIB breast cancer 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 first four cycles of therapy in patients who received the 24-hour infusion of paclitaxel (51% v 41%, respectively; P = .025), Tumor response over all cycles was also significantly higher in the group that received 24-hour infusion (51% v 44%, respectively; P = .023), There were no significant differences 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 were observed. During the first four cycles of therapy, at least one episode of greater than or equal to grade 3 toxicity (excluding nadir hematologic values, 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-hour paclitaxel infusion. Febrile neutropenia, greater than or equal to grade 3 infection, and greater than or equal to grade 3 stomatitis were less frequent, and severe neurosensory toxicity was more frequent in those who received the 3-hour paclitaxel infusion. Ten treatment-related deaths occurred in the first tour cycles. Age, stage, and prior chemotherapy did not influence the effect of treatment. Conclusion: When administered as a continuous 24-hour infusion, high-dose paclitaxel results in a higher tumor response rate-than when administered as a 3-hour infusion but does not significantly improve event-free survival or survival, paclitaxel as a 24-hour infusion results in increased hematologic toxicity and decreased neurosensory toxicity. (C) 1999 by American Society of Clinical Oncology.