Phase I trial of N-methylformamide (NMF, NSC 3051).
N-methylformamide (NMF) is a polar-planar solvent with both cytotoxic and differentiating activity in preclinical models; it also acts as a radiosensitizer. We treated 17 patients with 18 courses of NMF on a schedule of six weekly doses, administered on a rapid intravenous infusion, which were escalated from 875 to 2,000 mg/m2/wk. The predominant toxicity was a dose-related syndrome of fatigue, malaise, nausea, and anorexia, which was reflected by a decrease in performance status (Karnofsky) of greater than or equal to 20% in six of ten patients who received doses greater than or equal to 1,500 mg/m2/wk. Other gastrointestinal toxicities included moderate vomiting and mild diarrhea. Reversible increase of liver enzymes occurred in six of ten patients at doses greater than or equal to 1,500 mg/m2/wk. The maximum tolerated dose on this schedule is 1,500 mg/m2/wk; the dose recommended for phase II studies is 1,125 mg/m2/wk. Future studies of this regimen in a combined modality setting are planned.
D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D056486:Chemical and Drug Induced Liver Injury; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005559:Formamides / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008107:Liver Diseases / Q000097:blood; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D005559:Formamides; C002950:methylformamide