Combination chemotherapy in advanced lung cancer with increased survival

Twenty-eight patients with lung cancer, 26 with extensive disease, were treated with the drugs Cytoxan (Cyt) and methotrexate (MTX). The schedule was based on cellular kinetics concepts. Initial therapy was with Cyt 1.1 g/m2 (intravenously) followed by MTX 20 mg/m2 orally, twice weekly, started 9 days later, when the tumor was considered to be most susceptible to an S-phase-specific drug. The course was repeated at three-week intervals. Based on dose response curves, Cyt and MTX dose modifications were individually adjusted to the whit blood cell counts and platelet counts over a 3-week period. Twenty of 28 patients (five of seven large cell, five of eight adenocarcinoma, 10 or 11 small cell, none of two epidermoid) responded with greater than or equal 50% tumor reduction. Ten patients had complete responses, seven of whom had small cell carcinoma. Two of the nonresponders were nonevaluable. Five patients were alive and the extimated median survival time of the patients is almost 1 year, which compares quite favorably to previous reports. On this schedule of therapy, very high doses of Cyt and MTX were maintained with less than 3% incidence per course of a WBC less than 1,500/mm3 or a platelet count less than 50,000/mm3.