Cancer Chemotherapy and Pharmacology

, Volume 16, Issue 2, pp 139–147 | Cite as

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

  • Ernest S. Harpur
  • Simon P. Langdon
  • Serap A. K. Fathalla
  • John Ishmael
Original Articles cis-Platinum, N-Methylformamide
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Accepted:

Summary

N-Methylformamide (NMF), currently under-going 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.

Keywords

Sarcoma Clinical Evaluation Cytotoxic Effect Target Organ CDDP 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer-Verlag 1986

Authors and Affiliations

  • Ernest S. Harpur
    • 1
  • Simon P. Langdon
    • 2
  • Serap A. K. Fathalla
    • 1
  • John Ishmael
    • 3
  1. 1.Medical Research Council Mechanisms of Drug Toxicity Group, Pharmaceutical Sciences InstituteAston UniversityBirminghamUK
  2. 2.Cancer Research Campaign Experimental Chemotherapy Group, Pharmaceutical Sciences InstituteAston UniversityBirminghamUK
  3. 3.Imperial Chemical Industries PLC Central Toxicology LaboratoryNr MacclesfieldUK

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