Randomized phase III trial of paclitaxel/carboplatin (PC) versus cisplatin/irinotecan (CPT-P) as first-line chemotherapy in patients with clear cell carcinoma (CCC) of the ovary: A Japanese Gynecologic Oncology Group (JGOG)/GCIG study

Background: CCC is a histologic subtype of epithelial ovarian cancer showing different clinical and biological characteristics. CCC has become well known for its resistance to current standard chemotherapy (PC). Our previous trial demonstrated the potential benefit of CPT-P regimen on CCC. Methods: Patients (pts) with Stage I-IV CCC were randomized to receive paclitaxel 175mg/m2 plus carboplatin AUC6 IV q3wk or irinotecan 60mg/m2 IV (days 1, 8, 15) plus cisplatin 60mg/m2 IV (day 1) q4wk for 6 cycles. International central pathologic review was performed for all cases. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), response rate per RECIST, and adverse events. Adverse events were graded according to NCI-CTCAE, version 3.0. Results: From November 2006 to March 2011, 667 patients were registered, and 619 pts were clinically and pathologically eligible for evaluation (305 pts in PC arm and 314 pts in CPT-P arm). Median age was 53 years. Baseline pt characteristics were not significantly different. Following 44.3 months median follow-up, 2-years PFS was 73.0% (95% CI:67.7-77.5) in the CPT-P arm vs. 77.6% (95% CI:72.4-81.9) in the PC arm, which was not significantly different (HR:1.171, 95% CI:0.867-1.581, p=0.303). Two-years OS was 85.5% in CPT-P arm (95% CI:81.1-89.0) and 87.4% in PC arm (95% CI:83.1-90.7), respectively (HR:1.133, 95% CI:0.796-1.613, p=0.486). Grade 3/4 leukopenia, neutropenia, thrombocytopenia, peripheral sensory neuropathy and joint pain occurred more frequently in the PC arm, whilst grade 3/4 anorexia, diarrhea, nausea, vomiting and febrile neutropenia occurred more frequently in the CPT-P arm. Conclusions: In this first CCC-specific international clinical trial, survival benefit was not observed by CPT-P. Since both regimens were well tolerated and the toxicity profiles were different, CPT-P can be an alternative regimen for CCC.