Improved therapeutic index of methotrexate with "leucovorin rescue".

Abstract

Summary The effect of “leucovorin rescue” on the therapeutic index of methotrexate in epidermoid carcinomas of the head and neck was studied. Sixteen patients received maximally tolerated doses of methotrexate alone as 30-hr i.v. infusions at 2-week intervals and 44% responded. Significant hematological toxicity and 4 drug-related deaths were incurred. Twenty-five patients received higher doses of methotrexate followed by leucovorin rescue as 36- to 42-hr i.v. infusions every 2 weeks. This group experienced a response rate of 60% with fewer cases of severe toxicity. Seventeen of this group received more than 500 mg/sq m as a maximal dose and had a response rate of 76% with two drug-related deaths, while those receiving smaller doses had a response rate of only 25%. Serum methotrexate levels were proportional to the dose of drug. Leucovorin rescue enhances the therapeutic index of high-dose methotrexate infusions in epidermoid carcinomas of the head and neck.