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 ≥ 20% in six of ten patients who received doses ≥ 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 ≥ 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.