Phase II study of irinotecan plus oral etoposide in patients with platinum and taxane-resistant ovarian cancer

Abstract

5099 Background: Although there are many difficulties in the management for platinum-and taxane-resistant ovarian cancer patients, topoisomerase-1 inhibitor or oral etoposide (topoisomerase-2 inhibitor) has been chosen singly as a salvage therapy and showed 14–25% of response rate. Still we have no promising combination therapy for refractory ovarian cancer. Patients and Methods: We conducted a phase II study with the combination of irinotecan (topoisomerase-1 inhibitor) (60 or 70mg/m2 iv, day 1 and 15) and oral etoposide (50mg/body day 1–21) every four weeks. Cycles were repeated in the absence of progressive disease or prohibitive toxicity. Patients with advanced ovarian cancer who had prior-exposure to at least one platinum and taxane regimen, age 18–75, PS 0–2 and adequate organ function were eligible. Resistance to platinum and taxane was defined as progression during initial chemotherapy with platinum and taxane regimen, or relapsed within 6 months after completion of platinum and taxane regimen. Toxicity profile was assessed according to NCI-CTC ver.2 and response was measured by RECIST criteria or assessed by CA-125 (Rustin’s criteria). Response rate and toxicity were the primary endopoints and the progression free survival and over all survival were secondary endopoints. Results: Twenty-six patients entered the study. The median interval from the previous chemotherapy was 3 months. The median number of previous chemotherapeutic regimens was 2 (range: 1–4). Grade 3/4 hematologic toxicities included neutropenia (46% of patients), leukopenia (50%) and anemia (31%). Grade 3/4 non-hematologic toxicities included diarrhea (7.7%), and nausea/vomiting (15%). No treatment related death was observed. Twelve patients (46%) responded and seven patients (27%) demonstrated stabilization of their disease (PR+SD rate:73%). After a median follow-up of 11 months, progression free survival was 6 months (range: 1–18), duration of response was 6 months (0–17) and median survival was 9 months (2–20). Conclusions: The combination of irinotecan plus oral etoposide appears to have manageable toxicities and encouraging active regimen in patients with platinum-and taxane-resistant ovarian cancer. No significant financial relationships to disclose.