Cimetidine enhancement of cyclophosphamide antitumour activity

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Abstract

Male DBA2 mice were given 106 P-388 leukaemic cells i.p. and cimetidine (CMT) at 100 mg/kg 1 day for 10 days, or as a single 100mg/kg injection 30 min before cyclophosphamide (CTX). CMT significantly prolonged the survival of groups of mice receiving 50, 100 and 200 mg/kg of CTX 3 days after tumour inoculation. Median survival increased by 5.5 days (P<0.05), 10 days (P<0.05) and 13 days (P<0.05) respectively. The addition of CMT had the effect of roughly doubling the CTX dose, without increasing the lethality. CMT produced the only long-term survival seen in the study (1-2/10) CMT alone had no apparent antitumour activity. CMT significantly prolonged mean pentobarbital sleep to 28.6-60 min vs only 10 min for phenobarbital treated mice. Both CMT regimens increased the plasma concentration time products for CTX-induced metabolites (NBP) by about 1.3 fold (in contrast to a 33% reduction with phenobarbital). On average the single-dose CMT regimen produced the greatest effect on survival, on pentobarbital sleep duration and on total NBP reactive species. Probably mechanisms for the CMT-CTX interaction include competitive microsomal enzyme inhibition and/or acutely depressed hepatic blood flow. Caution should be used in combining CMT with full doses of CTX and any other highly metabolized antineoplastic agents in man.

Original languageEnglish (US)
Pages (from-to)35-43
Number of pages9
JournalBritish Journal of Cancer
Volume45
Issue number1
StatePublished - 1982

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Cimetidine
Cyclophosphamide
Survival
Pentobarbital
Phenobarbital
Sleep
Antineoplastic Agents
Injections
Liver

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Cimetidine enhancement of cyclophosphamide antitumour activity. / Dorr, Robert T; Alberts, David S.

In: British Journal of Cancer, Vol. 45, No. 1, 1982, p. 35-43.

Research output: Contribution to journalArticle

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