Phase I trial of 10-deaza-aminopterin in patients with advanced cancer.
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. Three escalating dose schedules were explored: single iv injections once daily, single iv injections twice weekly, and continuous infusion. The maximum tolerated doses were: single injections at a dose of 7 mg/m2/day for 5 days; single injections at a dose of 15 mg/m2 twice weekly for four to six doses; and continuous infusion at a dose of 3 mg/m2/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. Disease-oriented phase II trials are planned at this Center for several tumor varieties.
D000328:Adult; D000630:Aminopterin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001853:Bone Marrow / Q000187:drug effects; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005493:Folic Acid Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D007938:Leukemia / Q000188:drug therapy; D009092:Mucous Membrane / Q000187:drug effects; D012867:Skin / Q000187:drug effects
D005493:Folic Acid Antagonists; D000630:Aminopterin; C017178:10-deazaaminopterin