Because currently available chemotherapeutic agents are largely ineffective in the treatment of pancreatic cancer, novel treatments are urgently needed to improve outcomes in this disease. The purpose of this phase II study was to evaluate the anti-tumor activity of topotecan, a hydrophilic camptothecin analog that has demonstrated a wide range of anti-tumor activity in preclinical and phase I studies. Topotecan was administered as a 30 min infusion at a dose of 1.5 mg/m2/day for five consecutive days every 3 weeks, to chemotherapy-naive patients with advanced pancreatic cancer. Neutropenia was the principal toxicity of topotecan on this dosing schedule. No significant anti-tumor responses were observed in 27 patients with measurable disease. The median time to disease progression was 7 weeks and the median survival duration was 17.5 weeks. Thus, topotecan, administered on this schedule, is ineffective for patients with pancreatic carcinoma.