Phase I trial of N-methylformamide.

N-methylformamide was administered iv and later orally to 19 patients in a phase I study, with a starting dose of 300 mg/m2/day X 5. The cycles were planned to be repeated every 2 weeks, and doses were escalated in four steps to 1200 mg/m2/day X 5. The principal toxic effect of the drug was nausea and vomiting, but this was not severe enough to interfere with oral medication. Parallel bioavailability studies confirmed excellent absorption of the drug. Biochemical disturbances included reversible elevation in transaminases not related to dose, peripheral neuropathy in one patient, and drug interaction with alcohol in another. The dose-limiting toxic effect was reversible hyperbilirubinemia. One patient became jaundiced. Among 15 evaluable patients, there were two partial responses (prostate and cervix carcinoma) and two minimal responses (ovarian carcinoma and hypernephroma). The recommended dose for the phase II study is 800 mg/m2/day X 5 orally, repeated every 2 or 3 weeks.