Phase I trial of metoprine in patients with advanced cancer.
The effects of metoprine administered orally every 2 weeks were studied in 71 evaluable adult patients with advanced malignant tumors. Two escalating dose schedules were explored in this phase I evaluation: (a) doses ranging from 20 to 65 mg/m2 without scheduled leucovorin, and (b) doses ranging from 100 to 300 mg/m2 with scheduled iv leucovorin. Thrombocytopenia was dose-limiting at 65 mg/m2 in the low-dose schedule; CNS toxicity was dose-limiting at 300 mg/m2 in the high-dose schedule. Occasionally leukopenia and mild nausea or vomiting were noted. Therapeutic responses were observed in patients with mycosis fungoides, non-Hodgkin's lymphoma, and adenocarcinoma of unknown origin. Phase II (disease-oriented) studies can appropriately be initiated with fortnightly metoprine at 50 mg/m2 without leucovorin. In the high-dose schedule, 225 mg/m2 of metoprine with 75 mg/m2 of iv leucovorin at 24 hours appears appropriate for good-risk patients; in marginal-risk patients, two doses of leucovorin should be given: 75 and 37.5 mg/m2 at 24 and 96 or 168 hours, respectively.
D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy*; D011739:Pyrimethamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013921:Thrombocytopenia / Q000139:chemically induced
D000970:Antineoplastic Agents; C006308:metoprine; D002955:Leucovorin; D011739:Pyrimethamine