HIGH-DOSE MEGESTROL-ACETATE IN ADVANCED OR RECURRENT ENDOMETRIAL CARCINOMA - A GYNECOLOGIC-ONCOLOGY-GROUP STUDY

Purpose: Progestins represent the most widely used form of endocrine t herapy in advanced or recurrent endometrial carcinoma. Based on encour aging response rates in breast cancer with high-dose megestrol acetate (MA) 800 mg/d, this phase II trial assessed response rates in patient s with endometrial carcinoma treated with high-dose MA. Patients and M ethods: Sixty-three patients with recurrent or advanced endometrial ca rcinoma were entered into this Gynecologic Oncology Group (GOG) study. Patients had either failed to respond to or were considered incurable with local therapy and had not received prior cytotoxic or hormonal t herapy. MA 800 mg/d was administered orally in divided doses. Standard GOG toxicity criteria were used. Results: Of 63 patients entered, 58 were assessable for toxicity and 54 for response. Of 13 responders (24 %), six (11%) had a complete and seven (13%) a partial response. Four of the responses lasted greater than 18 months. Twelve patients (22%) had stable disease. The response rate of patients with grade 1 or 2 le sions (11 of 30, 37%) was significantly higher (P=.02) than that of pa tients with more poorly differentiated tumors (two of 24, 8%). There w as no difference in response rates comparing advanced versus recurrent disease, cell type, including papillary serous lesions, site of disea se, prior radiation, age, or weight. The median progression-free survi val (PFS) and overall survival intervals were 2.5 and 7.6 months, resp ectively. Grade 3 weight gain (> 20%) was seen in three patients and g rade 3/4 hyperglycemia in three. Three deaths secondary to cardiovascu lar events were possibly related to therapy; diabetes was also a contr ibuting factor in all three cases. Conclusion: High-dose MA is active in endometrial carcinoma, but appears to have no advantage over lower- dose progestins. (C) 1996 by American Society of Clinical Oncology.