Trimetrexate, a lipophilic, 2,4-diaminoquinazoline derivative of methotrexate, enters cells by passive diffusion rather than via a transport system. Trimetrexate has shown promising activity in animal model systems. A total of 16 patients with metastatic soft-tissue sarcoma who had received only one prior chemotherapy regimen were treated with trimetrexate (8 mg/m2 given intravenously daily for 5 days) every 3 weeks. Treatment-related toxicity included ≥ grade 2 neutropenia (8/16), thrombocytopenia (3/16), mucositis (4/16) and skin rash (3/16). No partial or complete responses were observed in 15 evaluable patients (95% confidence interval for true response rate, 0–22%) Six subjects showed stabilization of disease for periods ranging from 2 to 9 months. At this dose and on this schedule, trimetrexate appears to have little activity against refractory soft-tissue sarcomas.
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J. D. L. is supported by a physician-scientist award from the National Cancer Institute
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Licht, J.D., Gonin, R. & Antman, K.H. Phase II trial of trimetrexate in patients with advanced soft-tissue sarcoma. Cancer Chemother. Pharmacol. 28, 223–225 (1991). https://doi.org/10.1007/BF00685515
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