Phase II Evaluation of Oral Trimetrexate in Mixed Mesodermal Tumors of the Uterus: A Gynecologic Oncology Group Study

Abstract Objectives. This is a Phase II group-wide study of the Gynecologic Oncology Group to determine the toxicity and objective response rate of trimetrexate (TMTX) in patients with advanced, persistent, or recurrent mixed mesodermal tumors of the uterus who have failed higher priority treatment protocols. Methods. TMTX was administered orally at a dose of 5 mg/m 2 BID for 5 days and repeated in 14 days. The maximum total dose was 50 mg/m 2 /week given every other week. The minimum treatment period was one course. Patients who had a complete response, partial response, or stable disease were continued on treatment for at least three courses. Results. Twenty-eight patients were entered into the study. Three patients were ineligible based on review of pathologic materials. Twenty-five patients were evaluable for toxicity, and 21 were evaluable for response, as 4 patients did not complete one course of therapy. Eleven patients had heterologous mixed mesodermal tumor (MMT) and 10 had homologous MMT. Of the 25 evaluable for toxicity, one patient had grade 4 platelet toxicity. No patient had grade 4 neutropenia, while 4 patients had grade 3 decrease in absolute neutrophil count. One patient had grade 3 gastrointestinal toxicity, while 2 had grade 4 toxicity. There were no complete responses noted and only one partial response, for an overall response rate of 4.8%. The duration of the partial response was 15.2 months. Conclusion. Oral TMTX has insignificant activity in the treatment of advanced, persistent, and recurrent uterine MMT at the dose and schedule administered.