title: Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: a population-based study.
abstract: Metastasis is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) regulate invasion and metastasis. Several VGSC-inhibiting drugs reduce metastasis in murine cancer models. We aimed to test the hypothesis that patients taking VGSC-inhibiting drugs who developed cancer live longer than those not taking these drugs. A cohort study was performed on primary care data from the QResearch database, including patients with breast, bowel or prostate cancer. Cox proportional hazards regression was used to compare the survival from cancer diagnosis of patients taking VGSC-inhibiting drugs with those not exposed to these drugs. Median time to death was 9.7 years in the exposed group and 18.4 years in the unexposed group, and exposure to these medications significantly increased mortality. Thus, exposure to VGSC-inhibiting drugs associates with reduced survival in breast, bowel and prostate cancer patients. This finding is not consistent with the preclinical data. Despite the strengths of this study including the large sample size, the study is limited by missing information on potentially important confounders such as cancer stage, co-morbidities and cause of death. Further research, which is able to account for these confounding issues, is needed to investigate the relationship between VGSC-inhibiting drugs and cancer survival.
authors.affiliation: Department of Health Sciences, University of York, York, UK, YO10 5DD.
authors.forename: Caroline
authors.initials: C
authors.lastname: Fairhurst
authors.affiliation: Department of Health Sciences, University of York, York, UK, YO10 5DD.|Hull York Medical School, York, UK, YO10 5DD.
authors.forename: Ian
authors.initials: I
authors.lastname: Watt
authors.affiliation: Hull York Medical School, York, UK, YO10 5DD.|Department of Biology, University of York, York, UK, YO10 5DD.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Martin
authors.affiliation: Department of Health Sciences, University of York, York, UK, YO10 5DD.
authors.forename: Martin
authors.initials: M
authors.lastname: Bland
authors.affiliation: Department of Biology, University of York, York, UK, YO10 5DD.
authors.forename: William J
authors.initials: WJ
authors.lastname: Brackenbury
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000401:mortality*; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000401:mortality*; D012307:Risk Factors; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels