Trimetrexate: a phase 2 study in previously treated patients with metastatic breast cancer

Trimetrexate, a nonclassical antifolate, was administered to 28 patients with progressive, metastatic breast cancer. The starting dose was 8 mg/m2 administered intravenously (IV) as a short infusion daily for 5 days, repeated every 3 weeks with dose adjustments depending on patient tolerance. The median age of the 28 females in this study was 58.5 years. Their median performance status on the Zubrod scale was 1. Nine of the patients were estrogen-receptor positive. The sites of metastasis included the pulmonary system (50%), bone (40%), and liver (35%). Twenty patients were evaluable for response. Three patients (15%; [95% confidence interval 0.0, 30.6]) achieved a partial response with a median time to partial response of 9.1 weeks and a median duration of partial response of 13.1 weeks. Two of the responders were estrogen-receptor positive. Median survival for all 28 patients was 41 + weeks with 15 patients alive at the last follow-up. Hematologic grade 3-4 toxicity occurred as follows: leukopenia (21%), thrombocytopenia (18%), and granulocytopenia (18%). There was no significant nonhematologic toxicity seen.