Antihistamines and Ovarian Cancer Survival: Nationwide Cohort Study and in Vitro Cell Viability Assay

J Natl Cancer Inst. 2020 Sep 1;112(9):964-967. doi: 10.1093/jnci/djz217.

Abstract

Antihistamines with cationic amphiphilic drug (CAD) characteristics induce cancer-specific cell death in experimental studies. Epidemiologic evidence is, however, limited. In a Danish nationwide cohort of ovarian cancer patients diagnosed during 2000-2015 (n = 5075), we evaluated the association between filled antihistamine prescriptions and cancer mortality. We used Cox regression models to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for ovarian cancer mortality. In an in vitro cell viability assay, we evaluated cell death in three ovarian cancer cell lines after treatment with clinically relevant doses of eight antihistamines. In our cohort study, CAD antihistamine use (≥1 prescription; n = 133) was associated with a hazard ratio of 0.63 (95% CI = 0.40 to 0.99) compared to use of non-CAD antihistamines (n = 304), and we found a tendency toward a dose-response association. In our cell viability assay, we found consistent and dose-dependent cytotoxicity for all CAD but not non-CAD antihistamines. In this nationwide cohort study, use of antihistamines with CAD characteristics is associated with a prognostic benefit in ovarian cancer patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Ovarian Epithelial / complications
  • Carcinoma, Ovarian Epithelial / mortality*
  • Carcinoma, Ovarian Epithelial / pathology
  • Cations
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cohort Studies
  • Denmark / epidemiology
  • Drug Screening Assays, Antitumor
  • Female
  • Histamine Antagonists / pharmacology
  • Histamine Antagonists / therapeutic use*
  • Humans
  • Middle Aged
  • Mortality
  • Ovarian Neoplasms / complications
  • Ovarian Neoplasms / mortality*
  • Ovarian Neoplasms / pathology
  • Surface-Active Agents / pharmacology
  • Surface-Active Agents / therapeutic use*

Substances

  • Cations
  • Histamine Antagonists
  • Surface-Active Agents