Phase II trial of ZD1694 (TomudexTM) in patients with advanced pancreatic cancer
Currently available therapies for advanced pancreatic cancer offer only palliative benefits, and patients with this disease have a poor prognosis. We undertook a phase II trial of ZD1694 (TomudexTM), a quinazoline folate analogue that is a potent and selective thymidylate synthase inhibitor, to determine this analogue's efficacy and safety in patients with advanced pancreatic adenocarcinoma. ZD1694, 3.0 mg/m2, was administered to 42 adult patients with pancreatic adenocarcinoma as a 15-minute intravenous infusion every 3 weeks for up to 6 doses. Objective tumor response was assessed every 6 weeks; clinical examinations, adverse event assessments, and clinical laboratory tests were performed every 3 weeks. ZD1694 produced an overall response rate of 5% (95% confidence limits [CI], 1% to 16%) in the study group. Of 42 patients, 2 (5%) had a partial response, 12 (29%) had stable disease, 21 (50%) had disease progression, and 5 (11%) could not be evaluated for response. Grade 3 vomiting, grades 3 and 4 fever, grade 3 leukopenia, grade 4 thrombocytopenia, and grades 3 and 4 liver function elevations were reported. Toxic effects with ZD1694 were reversible and manageable. ZD1694 has an acceptable safety profile but limited activity in patients with advanced pancreatic cancer.