In vivo interaction of anti-cancer drugs with misonidazole or metronidazole: methotrexate, 5-fluorouracil and adriamycin

Abstract

I have studied the effects on growth of two tumours in mice and on host toxicity, of combining Misonidazole (MISO) or Metronidazole (METRO) with Methotrexate (MTX)-5-fluorouracil (FU) or Adriamycin (ADR). The nitroimidazoles alone had no effect on the growth of either tumour, but MISO (1 mg/g) led to a small increase in delay to regrowth of the 16/C mammary carcinoma but not the KHT fibrosarcoma, when given after X-irradiation. MTX was active only against the KHT tumour, and growth delay was not increased by the addition of MISO or METRO. FU delayed growth of both tumours, and growth delay was increased slightly by single-dose MISO. ADR was active only against the 16/C tumour, and delay to regrowth was increased by adding MISO. Host toxicity assessed by death and loss of body weight was much greater when MISO or METRO were added to MTX, and a little greater when they were added to FU. ADR plus MISO caused no deaths and no greater loss of body weight than ADR alone. The addition of MISO to treatment with anticancer drugs led to a slightly greater and more prolonged myelosuppression. METRO and MISO increase the anti-tumour effects of some anti-cancer drugs, but may also increase host toxicity. Nitroimidazoles should be used with caution in combination with chemotherapy.