Phase II Trial of Alternating Courses of Megestrol Acetate and Tamoxifen in Advanced Endometrial Carcinoma: a Gynecologic Oncology Group Study

Objectives: To estimate the objective response rate and toxicity associated with alternating megestrol acetate (MA) and tamoxifen citrate (T) in women with endometrial carcinoma.

Methods: Consenting patients with measurable recurrent or advanced endometrial carcinoma were eligible if they had not received prior cytotoxic or hormonal treatment. MA 80 mg BID x 3 weeks alternating with T 20 mg BID x 3 weeks orally was given.

Results: Of 61 patients entered, 56 eligible patients were evaluable for toxicity and response. Fifteen patients responded (12 complete, 3 partial) for an overall response rate of 27% (90% Confidence Interval: 17-38%). In 8 of 15 (53%) responders, response duration exceeded 20 months. The response rate was 38% in patients with histologic grade 1 tumors (n = 16), 24% in those with grade 2 disease (n = 17), and 22% among patients with grade 3 disease (n = 23). Women less than or equal to 60 years (n = 16) appear to have a better response rate than those >60 years (n = 40), 44% versus 20%. The response rate in patients with extra pelvic disease (n = 42) was 31% as compared to 14% in those with strictly pelvic and/or vaginal disease (n = 14). The median progression-free survival (PFS) was 2.7 months and median overall survival was 14.0 months. Two patients experienced a grade 4 thromboembolic event. Additional toxicities included one of each grade 3 gastrointestinal, grade 3 neurologic, and grade 3 genitourinary.

Conclusion: A regimen of alternating megestrol acetate and tamoxifen is active in treating endometrial cancer and may result in a prolonged complete response (CR) in some patients.