Oral medroxyprogesterone acetate in the treatment of advanced or recurrentendometrial carcinoma: A dose-response study by the Gynecologic Oncology Group

advanced or recurrent endometrial carcinoma. Both parenteral and oral proge stins yield similar serum levels and response rates, which range from 18% t o 34%. The one major study that used oral medroxyprogesterone acetate (MPA) noted a response rate at the lower end of the range (18%) and much poorer progression-free and overall survival times (4 and 10.5 months, respectivel y) than previously reported. The present study sought to confirm this earli er study of oral MPA, to assess the importance of prognostic factors such a s histologic: grade and receptor levels, and to determine whether a higher dose of MPA would yield a higher response rate. Patients and Methods: Two hundred ninety-nine eligible women with advanced or recurrent endometrial carcinoma were randomized ta receive oral MPA eith er 200 mg/d or 1,000 mg/d until unacceptable toxicity intervened dr their d isease progressed. Results: Among 145 patients receiving the low-dose regimen,there were 25 co mplete (17%) and 11 partial (8%) responses for an overall response rate of 25%. The 154 patients receiving the high-dose regimen experienced 14 (9%) c omplete and 10 (6%) partial responses far an overall response rate of 15%. Median durations of progression-free survival were 3.2 months and 2.5 month s for the low-dose and high-dose regimens, respectively. Median survival du rations were 11.1 months and 7.0 months, respectively. The adjusted relativ e odds of responding to the high-dose regimen compared with the low-dose re gimen was 0.61 (90% confidence interval, 0.36 to 1.04). prognostic factors having a significant impact on the probability of response included initial performance status, age, histologic grade, and progesterone receptor conce ntration. Compliance with oral therapy was documented with serum levels 1 m onth after starting therapy, when possible. MPA levels were commensurate wi th the assigned dose and schedule. Conclusion: Oral MPA is active against endometrial carcinoma. Response to p rogestin therapy is more frequent among patients with a well-differentiated histology and positive progesterone receptor status. This study provides n o evidence to support the use of MPA 1,000 mg/d orally instead of MPA 200 m g/d orally In fact, the trends suggest the opposite. The use of oral MPA 20 0 mg/d is a reasonable initial approach to the treatment of advanced or rec urrent endometrial carcinoma, particularly those lesions that are well-diff erentiated and/or progesterone receptor-positive(> 50 fmol/mg cytosal prote in). Patients with poorly differentiated and/or progesterone receptor level s less than 50 fmol/mg cytosol protein had only an 8% to 9% response rate. (C) 1999 by American Society of Clinical Oncology.