Tomudex (ZD1694, NSC 639186) in platinum-pretreated recurrent epithelial ovarian cancer: A phase II study by the Gynecologic Oncology Group

Purpose: Tomudex is a second-generation folate analogue that when polyglutamated is a potent inhibitor of thymidylate synthase (TS). Methods: Based on indications of antitumor activity in phase I trials, the Gynecologic Oncology Group initiated a phase II study of Tomudex 3 mg/m² intravenously every 3 weeks in patients with epithelial ovarian cancer, who had been pretreated with platinum drugs, and had subsequently recurred more than 6 months following such treatment. Results: Of 30 patients entered into the trial, 2 were pathologically ineligible, leaving 28 fully evaluable. In this patient population, Tomudex was generally well tolerated, but only three objective (partial) responses were documented. Conclusions: With the level of activity seen, the drug was not considered for further clinical development in ovarian cancer by the Gynecologic Oncology Group. However, it may be worthwhile to explore whether quantitation of TS could lead to selection of patients more likely to respond to this TS inhibitor.