Clinical Evaluation of High Intermittent Intravenous Doses of Methotrexate in Advanced Lung Cancer

Methotrexate (MTX) was given by weekly intravenous injections to 43 patients with inoperable or metastatic lung cancer (32 cases were untreated while 11 received radiotherapy or chemotherapy prior to administration of MTX). In 35 cases the dose was 40 mg/m²/week and in 8 cases 60 mg/m²/week. 36 patients were adequately evaluable. In most cases it was possible to continue the administration of MTX for 6–8 weeks (table 1). In responsive cases maintenance treatment was given at the dose of 15 mg/m² every 4 days either orally or intramuscularly. Response to treatment was evaluated according to Karnofsky's scale. Considering only the category I responses 12/30 patients adequately treated with 40 mg/m² showed objective improvement and 2/6 of those given 60 mg/m². Regressions were short-lived and in no case did they last longer than 5 months (table 2). Regressions were seen in practically all histologic types (table 3). Of 43 patients receiving MTX 30 (70%) had one or more side-effects: 27 showed oral or gastrointestinal toxicity, 8 varying degrees of bone marrow depression, 6 hepatic and 4 renal toxicity. Four patients died because of toxicity, renal damage being present in all cases (table 4). The relatively small number of consistent objective regressions (about 40%), their short duration and the high incidence of severe toxicity, as observed in the present series, indicate that weekly high-dose intravenous MTX is of moderate therapeutic usefulness in lung cancer.