Increased therapeutic index using moderate dose methotrexate and leucovorin twice weekly vs. weekly high dose methotrexate-leucovorin in patients with advanced squamous carcinoma of the head and neck: a safe new effective regimen.

A new intensive methotrexate regimen for the treatment of advanced squamous carcinoma of the head and neck is presented, employing twice-weekly parenteral low-moderate doses of methotrexate and a single parenteral dose of leucovorin 24 hours following methotrexate. Toxicity and therapeutic results in 20 patients treated with this regimen favorably with results of weekly high-dose methotrexate-leucovorin in 36 patients treated immediately before initiation of the new regimen. Moderate nephrotoxicity and mild gastrointestinal/mucosal toxicity were common to both, while myelotoxicity was rarely seen with the low dose regimen and was more frequent with the high-dose regimen. Partial response was observed in 60% of patients treated on the intensive low-moderate dose schedule, and 50% of patients previously untreated with methotrexate on the weekly high-dose schedule. None of 12 patients previously failing low-moderate doses of methotrexate responded to high doses administered in this trial. The characteristics of antitumor response with low-moderate and high-dose schedules were similar except for the median dose required to attain response (50 mg/m2 vs. 3 g/m2) and the lesser toxicity of intensive lower dose therapy with leucovorin.