PHASE-II TRIAL OF ZD1694 (TOMUDEX(TM)) IN PATIENTS WITH ADVANCED PANCREATIC-CANCER

Background: Currently available therapies for advanced pancreatic canc er offer only palliative benefits, and patients with this disease have a poor prognosis. We undertook a phase II trial of ZD 1694 (Tomudex(T M)), a quinazoline folate analogue that is a potent and selective thym idylate synthase inhibitor, to determine this analogue's efficacy and safety in patients with advanced pancreatic adenocarcinoma. Patients a nd methods: ZD1694, 3.0 mg/m(2), was administered to 42 adult patients with pancreatic adenocarcinoma as a 15-minute intravenous infusion ev ery 3 weeks for up to 6 doses. Objective tumor response was assessed e very 6 weeks; clinical examinations, adverse event assessments, and cl inical laboratory tests were performed every 3 weeks. Results: ZD 1694 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 re sponse, 12 (29%) had stable disease, 21 (50%) had disease progression, and 5 (11%) could not be evaluated for response. Grade 3 vomiting, gr ades 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. Conclusions: ZD1694 has an acceptable safety profile but limited activity in patients with advan ced pancreatic cancer.