RANDOMIZED TRIAL OF INITIAL THERAPY WITH MELPHALAN VERSUS CISPLATIN-BASED COMBINATION CHEMOTHERAPY IN PATIENTS WITH ADVANCED OVARIAN-CARCINOMA - INITIAL AND LONG-TERM RESULTS - EASTERN-COOPERATIVE-ONCOLOGY-GROUP STUDY E2878

BACKGROUND. Following surgical debulking, most patients with Internati onal Federations of Gynecology and Obstetrics (FIGO) Stage III or IV c arcinoma of the ovary receive treatment with combination chemotherapy. However, the optimal postsurgical therapy for ovarian carcinoma remai ns to be defined. METHODS. To define better the role of initial therap y with a cisplatin-based chemotherapy regimen, the Eastern Cooperative Oncology Group (ECOG) initiated a randomized, Phase III trial, EST 28 78, comparing initial therapy with a single, orally administered alkyl ating agent, melphalan, versus a complex regimen employing cyclophosph amide, hexamethylmelamine, doxorubicin, and cisplatin (CHAD). Women wh o failed treatment with melphalan were crossed-over to treatment with CHAD minus the cyclophosphamide (HAD). Study endpoints included respon se to therapy, time to treatment failure, and overall survival. RESULT S. Between October, 1978, and November, 1980, EST 2878 accrued 253 pat ients with advanced epithelial carcinoma of the ovary. There were 118 eligible patients initially treated with melphalan and 126 with CHAD. Two patients experienced lethal toxicities, including gastrointestinal hemorrhage (1 patient) and neutropenic sepsis (1 patient), and 22 pat ients experienced life-threatening toxicities, including hematologic t oxicity (21 patients) and anaphylaxis (1 patient). Response to treatme nt and clinical complete response rates were higher in women receiving CHAD (60% and 38%, respectively) versus melphalan (42% and 21%, respe ctively) (P = 0.037 and P = 0.024, respectively), but these difference s were confined to women older than 50 years of age. Likewise, time to treatment failure was significantly longer in women receiving CHAD (P = 0.014), but the difference was again confined to women older than 5 0 years of age and to women suboptimally debulked at the time of surge ry. Survival did not differ between the two arms (median survivals of 17.5 months with initial melphalan therapy and 19.5 months with CHAD), probably because women treated initially with melphalan received salv age therapy with HAD. Twenty-three patients survived longer than 10 ye ars. Among 18 long term survivors who had retrospective pathologic rev iew, 8 had borderline tumors of the ovary. CONCLUSIONS. In women with advanced ovarian cancer, initial therapy with a cisplatin-based combin ation chemotherapy regimen resulted in higher clinical complete respon se rates and longer time to failure compared with initial therapy with a single, oral alkylating agent; however, the benefits of this approa ch were confined to women older than 50 years of age at diagnosis, and there was no significant difference in survival. (C) 1996 American Ca ncer Society