The role of combination chemotherapy regimens in the management of ovarian cancer patients with tumors resistant to platinum compounds has not yet been defined. This multicenter prospective phase II study evaluated the activity and toxicity of the docetaxel-plus-irinotecan combination in ovarian cancer patients whose tumors were resistant to platinum compounds and who had been exposed to paclitaxel. Treatment consisted of docetaxel 60 mg/m2 i.v. followed by irinotecan 200 mg/m2 i.v. both on day 1 followed by prophylactic recombinant human granulocyte-colony stimulating factor (rhG-CSF) support from days 2 to 6, every 3 weeks. Thirty-one patients were enrolled in the study. The median age was 60 years, and the median performance status (ECOG) was 1. Eight (26%) patients had primary tumors resistant to platinum, while the rest of the population had tumor recurrence within 6 months from the last cisplatin treatment. Four chemotherapy cycles per patient were administered, with the delivered dose intensity at 75% of the planned dose for both agents. Among 30 patients evaluable for response, there were 2 (7%) complete and 4 (14%) partial responses (overall response rate 20%; (95% confidence interval, CI, 11%-33%). Stable disease was recorded in 8 (28%) patients and progressive disease in 15 (51%). The median response duration was 4.5 months (range, 3-12), the median time to progression 5 months (range, 2-17) and the median survival 11 months (range, 1-40); the 1-year survival was almost 50%. Myelotoxicity was moderate, with grade 3 and 4 neutropenia occurring in 23% of the patients, grade 3-4 thrombocytopenia in 6% and febrile neutropenia in 13%. Grade 3 diarrhea was observed in 2% of the patients. There was one treatment-related death due to sepsis. In conclusion, the combination of docetaxel plus irinotecan with rhG-CSF support, appears to be a moderately effective regimen with acceptable toxicity for platinum-resistant, paclitaxel-pretreated ovarian cancer patients. Further investigation in comparative studies is required to define the role of combination versus single agent chemotherapy in this group of patients.