High-dose platinum versus standard dose in advanced ovarian carcinoma: A randomized trial from the Gynecologic Cooperative Group of the French Comprehensive Cancer Centers (FNCLCC)

Objective. The aim of this study was to evaluate the impact of platinum dos e intensity on pathological response rate and overall survival in patients with advanced ovarian adenocarcinoma. Methods. Between February 1992 and December 1996, 195 previously untreated patients with FIGO stage IIb-c, IIIb-c, or IV with macroscopic residual dis ease after suboptimal debulking surgery were randomized to receive CCC (100 mg/m(2) of cisplatin, 300 mg/m(2) of cyclophosphamide, 300 mg/m(2) of carb oplatin, n = 96) or CC (100 mg/m(2) of cisplatin, 600 mg/m(2) of cyclophosp hamide, n = 99) for six courses at 28-day intervals. A second-look laparoto my was planned at the end of chemotherapy, Results. In the CCC arm, the platinum compound received dose intensity and relative total dose were 85 and 76%; in the CC arm, they were 94 and 85%. G rade 3-4 toxicity was more frequent in the CCC arm than in the CC arm for l eukopenia (56% vs 26%, P < 0.001), febrile neutropenia (18% vs 4%, P = 0.00 2), anemia (31% vs 5%, P < 0.001), thrombopenia (55% vs 4%, P < 0.001), and ototoxicity (8% vs 0%, P < 0.001), The pathologic complete response rate w as 22 and 14% in the CCC and CC arms, respectively (P = 0.19). With a media n follow-up of 53 months, the median time to failure and the 3-year treatme nt failure-free survival rate were 17.4 months and 22% vs 13 months and 11% in the two arms, respectively (P = 0.01). The median survival time and the 3-year overall survival rate were, respectively, 30 months and 42% vs 25 m onths and 33% (P < 0.20). Conclusion. The platinum dose intensification (1.6-fold increase) obtained with the CCC association improves the treatment failure-free survival witho ut significant impact on overall survival when compared with the CC regimen in suboptimal debulked ovarian adenocarcinoma. However, because of its hig h rate of hematologic toxicity and ototoxicity, this association cannot be recommended for routine practice. (C) 2000 Academic Press.