A phase II trial of pemetrexed in combination with carboplatin in patients with recurrent ovarian or primary peritoneal cancer

Abstract Objective Carboplatin-based combinations are commonly used in platinum-sensitive ovarian cancer (PSOC). Pemetrexed in combination with carboplatin has been shown to be feasible in a phase I study in PSOC. The primary objective of this subsequent phase II study was to determine the overall response rate (ORR; defined by Response Evaluation Criteria in Solid Tumors) of this combination in patients with recurrent PSOC. Secondary objectives included progression-free survival (PFS), overall survival (OS), and toxicity. Methods Patients with PSOC (defined by recurrence ≥6months after completion of up to two lines of prior platinum-based therapy), measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. Pemetrexed 500mg/m 2 was administered as a 10-minute infusion followed by carboplatin AUC 6 as a 30-minute infusion on day 1 of a 21-day cycle. Results Sixty-six patients were treated. Of the 61 patients evaluable for response, there were 20 responders (one complete response and 19 partial responses), for an ORR of 32.8% (95% CI: 21.3%, 46.0%). For the intent-to-treat population (all 66 patients), the median PFS was 9.4months (95% CI: 8.3, 11.1), with 22.7% censoring. Median OS was not reached due to the high censoring rate. There was one drug-related death (multi-organ failure). The most common drug-related grade 3/4 toxicities were neutropenia (39.4%), thrombocytopenia (24.2%), carboplatin hypersensitivity (9.1%), nausea (6.1%), and vomiting (6.1%). Conclusions Carboplatin AUC 6 and pemetrexed 500mg/m 2 has a low incidence of serious toxicities. Defining the platinum-based combination with the best therapeutic index would require a prospective phase III study.