PHASE-I TRIAL OF 10-DEAZA-AMINOPTERIN IN PATIENTS WITH ADVANCED CANCER

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  • 1 January 1983
    • journal article
    • research article
    • Vol. 67  (2) , 149-154
Abstract
The clinical effects of 10-deaza-aminopterin, an inhibitor of dihydrofolate reductase with a better therapeutic index against several murine tumors than that of methotrexate, were examined during the course of a phase I study in patients with advanced malignant neoplasms. The following 3 escalating dose schedules were explored: single i.v. injections once daily, single i.v. injections twice weekly, and continuous infusion. The maximum tolerated doses were as follows: single injections at a dose of 7 mg/m2 per day for 5 days; single injections at a dose of 15 mg/m2 twice weekly for 4-6 doses; continuous infusion at a dose of 3 mg/m2 per day for 5-6 days in patients with solid tumors and until bone marrow hypoplasia in patients with leukemia. Mucositis was dose-limiting in all schedules. Occasionally, mild leukopenia, thrombocytopenia and skin rash were noted. A minor antitumor response was seen in a patient with gallbladder carcinoma. Marked leukemic cell kill was observed in several patients with acute leukemia or blastic phase of chronic myelogenous leukemia.