Combination of ametopterine (MTX) and cyclophosphamide (CPM) based on the principle of partial synchronization of cell proliferation in lung cancer. Phase II study.

Twenty-three patients with histologically proven bronchogenic carcinoma of the lung were treated with regimen consisting of 3 intravenous doses of 0.4 mg/kg of MTX and intravenous infusion of 30-50 mg/kg body weight of CPM. Interval between 1st and 2nd dose of MTX, which served as synchronizing agent in phase G1/S, was 12 hrs, and interval between 2nd and 3rd dose -- 6 hrs. Infusion of CPM, which was considered to be a preferably S-phase killer was started simultaneously with administration of 3rd dose of MTX. Such courses were repeated every 21-30 days. Objective responses were noted in 10 of 19 adequately treated patients. MTX-CPM favourably influenced survival of the responders. The therapy was, however associated with a number of adverse reactions, from which neutropenia and complicating bacterial infections were particularly dangerous.