TY - JOUR

T1 - Antihistamines and ovarian cancer survival

T2 - nationwide cohort study and in vitro cell viability assay

AU - Verdoodt, Freija

AU - Dehlendorff, Christian

AU - Jäättelä, Marja

AU - Strauss, Robert

AU - Pottegård, Anton

AU - Hallas, Jesper

AU - Friis, Søren

AU - Kjær, Susanne K

PY - 2020

Y1 - 2020

N2 - 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 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 HR of 0.63 (95% CI: 0.40 to 0.99) compared to use of non-CAD antihistamines (n = 304), and we found a tendencytowards 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.

AB - 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 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 HR of 0.63 (95% CI: 0.40 to 0.99) compared to use of non-CAD antihistamines (n = 304), and we found a tendencytowards 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.

U2 - 10.1093/jnci/djz217

DO - 10.1093/jnci/djz217

M3 - Journal article

C2 - 31688928

VL - 112

SP - 964

EP - 967

JO - National Cancer Institute. Journal (Print)

JF - National Cancer Institute. Journal (Print)

SN - 0027-8874

IS - 9

ER -