Phase II study with sequential l-asparaginase and methotrexate in advanced refractory breast cancer

The combination of sequential L-asparaginase and methotrexate (MTX) was evaluated in 33 patients with advanced refractory breast cancer. There were nine partial responses and one complete response, giving an overall response rate of 30% and a median duration of response of 8 months. Five of 17 patients (28%) who had received prior MTX at doses of <50 mg/m ³ responded. Toxicity was acceptable. Moderate-to-severe stomatitis occurred in most patients and was the dose-limiting factor. Myelosuppression was minimal until the dose of MTX was escalated to ≥ 180 mg/m ². The maximum tolerated dose of MTX was 280 mg/m ² and the median toxic dose was 220 mg/m ². These data indicate a selective 'rescue' from MTX damage to normal target tissue by L-asparaginase. The antitumor effect observed even in patients who had been previously exposed to conventional doses of MTX suggests a possible improved therapeutic index of MTX given sequentially with L-asparaginase in this combination.