The antitumour effect and toxicity of cis-platinum and N-methylformamide in combination

N-Methylformamide (NMF), currently undergoing phase II clinical evaluation for the treatment of cancer, and the established antitumour agent cis-platinum (CDDP) have nonoverlapping toxicities, with the exception of gastrointestinal side effects. The major target organs for the toxicities of the compounds are the liver (NMF) and the kidney (CDDP). Furthermore, NMF is nonleukopenic. In view of this, and of recent evidence that NMF enhances the cytotoxic effect of CDDP in vitro the activity of NMF and CDDP against the M5076 sarcoma implanted in mice was investigated, together with the various toxicities in mice and rats. The antitumour effect of NMF in combination with CDDP was additive, but NMF did not alter the leukopenia produced by CDDP in the tumour-bearing mice. CDDP produced only a minimal increase in the hepatotoxicity of NMF in mice, and NMF did not augment the nephrotoxicity of CDDP in rats (except for a small effect on calcium excretion). The results support suggestions that clinical evaluation of combination chemotherapy with NMF and CDDP is warranted.