Summary
The combination of the histamine H2 antagonist cimetidine (CMT) and the anticancer agent cisplatin (CDDP) was studied in normal and tumorbearing mice. CMT doses of 100 mg/kg produced no alteration in the survival of DBA/2J mice bearing P-388 leukemia treated with CDDP doses of 3 mg/kg or 6 mg/kg. In these groups, the median survival was 13 days and 16 days, respectively, compared to 10 days in untreated controls. However, when adult CD-1 mice were given higher but nonlethal CDDP doses of 10, 15, or 18 mg/kg, the addition of CMT significantly increased CDDP lethality (P<0.05 by Wilcoxon analysis). For the 3 groups, CMT-inhanced lethality occurred in 10% of mice given 10 mg/kg CDDP, 80% of mice given 15 mg/kg, and 100% of mice given 18 mg/kg CDDP. Thus, CMT can acutely alter CDDP toxicity without affecting antitumor efficacy in mice.
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Dorr, R.T., Soble, M.J. Cimetidine enhances cisplatin toxicity in mice. J Cancer Res Clin Oncol 114, 1–2 (1988). https://doi.org/10.1007/BF00390477
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DOI: https://doi.org/10.1007/BF00390477