PHASE-II TRIAL OF TRIMETREXATE IN ADVANCED ESOPHAGEAL CANCER - A SOUTHWEST-ONCOLOGY-GROUP STUDY

Trimetrexate (TMQ) is a synthetic folate antagonist that has demonstra ted non-cross resistance with methotrexate in preclinical screens. A p hase II trial was performed with TMQ given to patients with advanced s quamous cell carcinoma of the esophagus. TMQ was administered as an i. v. bolus on a daily x 5 schedule, every 3 weeks; a starting dose of 12 mg/m(2) was used for patients with no prior irradiation, and of 8 mg/ m(2) for patients with prior irradiation. Twenty-four patients were en tered onto study, with 23 patients eligible, and a median of 2 courses of TMQ administered per patient. Twenty-three patients were evaluable for toxicity. Toxicities of SWOG grade greater than or equal to 3 inc luded granulocytopenia (9 patients), leukopenia (7 patients), thromboc ytopenia (4 patients), anemia (3 patients), mucositis (3 patients), na usea and vomiting (2 patients), dermatitis (1 patient), diarrhea (1 pa tient), and fever (1 patient). Fifteen patients had some hematologic t oxicity, and eleven patients had hematologic toxicity of grade greater than or equal to 3. Two treatment related deaths occurred in associat ion with myelosuppression. One patient achieved a complete response an d one patient achieved a partial response, with response durations of 8.5 months and 6 months, respectively. The overall response rate was 8 % [95% confidence interval of 1 to 28%], with a median survival for th e 23 eligible patients of 5.1 months.