Trimetrexate glucuronate in combination therapy with cisplatin or etoposide was evaluated in non-small cell lung cancer patients in a pilot, dose escalation study. Trimetrexate was administered intravenously together with 20 mg/m2 cisplatin or 50 mg/ m2 etoposide for 5 consecutive days at an initial dose of 4 mg/m2. Courses were repeated at 3 week intervals with the trimetrexate dosage escalated according to patient tolerance. In the 12 patients treated to date, reversible myelosuppression, consisting of leukopenia and thrombocytopenia, and nonhematologic grade 1 and 2 toxicities were observed. The study is ongoing. The maximum tolerated trimetrexate dosage levels in combination therapy will be established. © 1988.