Despite the high objective response rate of advanced ovarian cancer to combination platinum/taxane-based chemotherapy, the majority of patients ultimately experience disease progression. Thus, there is a need to find new management strategies that can improve upon the results of existing therapies. We are currently conducting a phase II trial to explore the toxicity and potential efficacy of a three-drug program, which adds irinotecan (CPT-11, Camptosar) at 100 mg/m2 to carboplatin (Paraplatin) at an area under the concentration-time curve of 5 and paclitaxel at 150 mg/m2 over 3 hours. Treatment was initially given on an every-3-week schedule, but was subsequently changed to an every-4-week schedule due to excessive bone marrow toxicity. The study remains in progress, with 26 patients currently evaluable for toxicity, which has included grade 4 neutropenia (42% incidence), grade 4 thrombocytopenia (12%), and grade 3 emesis (12%), with one patient each experiencing grade 3 diarrhea, hepatic dysfunction, and insomnia. Data regarding response rates are immature. Our preliminary analysis reveals that the combination of carboplatin/paclitaxel/irinotecan can be administered to women with advanced ovarian cancer with significant, but overall acceptable, toxicity. Randomized trials will be required to define a possible role for this three-drug combination chemotherapy regimen in the standard management of advanced ovarian cancer.