Fifty consecutive patients with documented advanced or recurrent endometrial carcinoma from 1978 through 1985 were prospectively treated with melphalan, 5-fluorouracil, medroxyprogesterone acetate (MFP) as first-line chemotherapy. From 1987 through 1993, 50 consecutive patients with documented advanced or recurrent endometrial carcinoma were prospectively treated with cisplatin, Adriamycin, etoposide, megestrol acetate (PAV-M) as first-line chemotherapy. Response rates for MFP versus PAV-M, 2- and 5-year survival, median survival, 2- and 5-year progression-free survival, and median progression-free survival were not statistically different. However, there was a significant improvement favoring PAV-M in 2-year (45 versus 14%), 5-year (30 versus 5%), and median survival (22.3 versus 8.7 months) (P = 0.008) compared to MFP in patients with primary advanced endometrial adenocarcinoma. Moreover, there was a significant improvement in 2- and 5-year and median survival (55 and 15% and 26.7 months) for PAV-M compared to MFP (7 and 0% and 7.3 months) (P = 0.002) for the more aggressive other adenocarcinomas (adenosquamous, clear cell, papillary serous, undifferentiated) compared to the more common endometrioid adenocarcinoma. The current data suggest that cisplatin- and adriamycin-based chemotherapy results in some long-term survival benefit for patients with primary advanced endometrial adenocarcinoma and the more aggressive nonendometrioid adenocarcinoma histologies.