Second-Line Irinotecan and Carboplatin for Advanced Ovarian Cancer: Phase 1
Second-Line Irinotecan and Carboplatin for Advanced Ovarian Cancer: Phase 1
Abstract & Commentary
By William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC and is Editor of Clinical Oncology Alert. Dr. Ershler is on the speaker’s bureau for Amgen and does research for Ortho Biotech.
Synopsis: In a phase I trial for patients with advanced ovarian cancer, irinotecan and carboplatin were administered at 6 different dose levels to determine maximum tolerated dose. The dose-limiting toxicity was hematologic (neutropenia and thrombocytopenia). The recommended dose for the Phase II study was irinotecan 60 mg/m2 on Days 1, 8, and 15 and carboplatin 5 mg/mL (AUC) on day 1, repeated every 4 weeks. Of note, of the ten patients with measurable disease, criteria for treatment response were achieved in 5. This level of response bodes well for this combination.
Source: Yonemori K, et al. A phase I study and pharmacologic evaluation of irinotecan and carboplatin for patients with advanced ovarian carcinoma who previously received platinum-containing chemotherapy. Cancer. 2005;104:1204-1212.
Ovarian cancer is the leading cause of death from malignancy in women. Although 60 to 80 percent of women with advanced ovarian cancer treated with platinum-containing chemotherapy initially respond, the responses for many are only temporary. Thus, a focus of clinical research remains the definition of optimal treatment for relapsed patients.
The purpose of the current study was to establish the maximum tolerated dose (MTD) for irinotecan and carboplatin when used in combination for patients with advanced ovarian cancer who had received prior platinum-based therapy. Additionally, pharmacokinetic and pharmacodynamic studies were performed.
Irinotecan (CPT-II), a DNA topoisomerase I inhibitor, has proven useful in the setting of drug resistance, and preliminary evidence has suggested potential synergism with carboplatin. Ovarian cancer patients with active disease who had prior platinum-containing chemotherapy, whether platinum-sensitive or platinum-resistant, were enrolled (n = 19) between August 1996 through July 1999. Carboplatin was administered as a 60 minute intravenous infusion on Day 1 and was followed by irinotecan, which was administered as a 90-minute infusion on Days 1, 8, and 15. Six different dose levels of the 2 drugs were explored.
The dose limiting toxicities were hematologic (Grade 4 neutropenia and/or thrombocytopenia). The response to therapy was assessed using World Health Organization (WHO) criteria and 5 of the 10 patients with measurable disease were found to have an objective response.
Based on these results, irinotecan and carboplatin appear to be a reasonable option for women with advanced ovarian cancer who have already received platinum based chemotherapy. The recommended dose for Phase II investigation is irinotecan 60 mg/m2 on Days 1, 8, and 15 with carboplatin given on day 1. The dose of Carboplatin based on the Chatelut formula, was 5 mg/mL (AUC) on Day 1 repeated every 4 weeks.
Commentary
By design, this was a Phase 1 trial with a goal of determining MTD was achieved by standard clinical trial methodology. It is noteworthy that half of the patients with measurable disease met established criteria for response. Thus, the rationale for a Phase II trial with this combination is strengthened, both for those who have demonstrated platinum resistance and for those who have not.
In a phase I trial for patients with advanced ovarian cancer, irinotecan and carboplatin were administered at 6 different dose levels to determine maximum tolerated dose. The dose-limiting toxicity was hematologic (neutropenia and thrombocytopenia). The recommended dose for the Phase II study was irinotecan 60 mg/m2 on Days 1, 8, and 15 and carboplatin 5 mg/mL (AUC) on day 1, repeated every 4 weeks. Of note, of the ten patients with measurable disease, criteria for treatment response were achieved in 5. This level of response bodes well for this combination.Subscribe Now for Access
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