BACKGROUND: 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 (Tomudex), 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: ZD1694 has an acceptable safety profile but limited activity in patients with advanced pancreatic cancer.
BACKGROUND: 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 (Tomudex), 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. PATIENTS AND METHODS: 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. RESULTS: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. CONCLUSIONS:ZD1694 has an acceptable safety profile but limited activity in patients with advanced pancreatic cancer.
Authors: R A Wolff; P Chiao; R Lenzi; P W Pisters; J E Lee; N A Janjan; C H Crane; D B Evans; J L Abbruzzese Journal: Invest New Drugs Date: 2000-02 Impact factor: 3.850
Authors: M Reni; L Pasetto; G Aprile; S Cordio; E Bonetto; S Dell'Oro; P Passoni; L Piemonti; C Fugazza; G Luppi; C Milandri; R Nicoletti; A Zerbi; G Balzano; V Di Carlo; A A Brandes Journal: Br J Cancer Date: 2006-03-27 Impact factor: 7.640
Authors: J J Arends; H P Sleeboom; M B L Leys; D Ten Bokkel Huinink; R S de Jong; J M Smit; J W R Nortier; M E T Tesselaar Journal: Br J Cancer Date: 2005-02-14 Impact factor: 7.640
Authors: I Judson; T Maughan; P Beale; J Primrose; P Hoskin; J Hanwell; C Berry; M Walker; F Sutcliffe Journal: Br J Cancer Date: 1998-11 Impact factor: 7.640