Dose-response trial of megestrol acetate in advanced breast cancer: Cancerand leukemia group B phase III study 8741

Purpose: To investigate whether dose escalation of megestrol acetate (MA) i mproves response rate and survival in comparison with standard doses of MA. Patients and Methods: Three hundred sixty-eight patients with metastatic br east cancer, positive and/or unknown estrogen and progesterone receptors, z ero or one prior trial of hormonal therapy and no prior chemotherapy for me tastatic disease were prospectively randomized into three groups. The group s of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day). Results: patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were includ ed in the analyses. The response rates were 23%, 27%, and 27% For the 160-m g, 800-mg, and 1,600-mg arms, respectively. Response duration correlated in versely with dose, Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively No sig nificant differences in the treatment arms were noted for time to disease p rogression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The mast frequent and troubles ome toxicity, weight gain, was dose-related, with approximately 20% of pati ents on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm. Conclusion: With a median follow-up of 8 years, these results demonstrate n o advantage for dose escalation of MA in the treatment of metastatic breast cancer. J Clin Oncol 17:64-73, (C) 1999 by American Society of Clinical Oncology.