Sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the CPRD primary care database.
Voltage-gated sodium channel (VGSC)-inhibiting drugs are commonly used to treat epilepsy and cardiac arrhythmia. VGSCs are also widely expressed in various cancers, including those of the breast, bowel and prostate. A number of VGSC-inhibiting drugs have been shown to inhibit cancer cell proliferation, invasion, tumour growth and metastasis in preclinical models, suggesting that VGSCs may be novel molecular targets for cancer treatment. Surprisingly, we previously found that prior exposure to VGSC-inhibiting drugs may be associated with reduced overall survival in patients with cancer, but we were unable to control for the cause of death or indication for prescription. The purpose of the present study is to interrogate a different database to further investigate the relationship between VGSC-inhibiting drugs and cancer-specific survival.



A cohort study using primary care data from the Clinical Practice Research Datalink database will include patients with diagnosis of breast, bowel and prostate cancer (13 000). The primary outcome will be cancer-specific survival from the date of cancer diagnosis. Cox proportional hazards regression will be used to compare survival of patients taking VGSC-inhibiting drugs (including antiepileptic drugs and class I antiarrhythmic agents) with patients with cancer not taking these drugs, adjusting for cancer type, age and sex. Drug exposure will be treated as a time-varying covariate to account for potential immortal time bias. Various sensitivity and secondary analyses will be performed.



The project has been reviewed and approved by the University of York Ethical Review Process. Results will be presented at an international conference and published in open access peer-reviewed journals according to the STROBE and RECORD guidelines.
Department of Health Sciences, University of York, York, UK.
Caroline
C
Fairhurst
Hull York Medical School, York, UK Department of Biology, University of York, York, UK.
Fabiola
F
Martin
Department of Health Sciences, University of York, York, UK Hull York Medical School, York, UK.
Ian
I
Watt
Department of Health Sciences, University of York, York, UK.
Tim
T
Doran
Department of Health Sciences, University of York, York, UK.
Martin
M
Bland
Department of Biology, University of York, York, UK.
William J
0000-0001-6882-3351
WJ
Brackenbury
D000328:Adult; D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000401:mortality*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011320:Primary Health Care; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality*; D012107:Research Design; D012189:Retrospective Studies; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D016019:Survival Analysis; D006113:United Kingdom / Q000453:epidemiology
D000889:Anti-Arrhythmia Agents; D000927:Anticonvulsants; D026941:Sodium Channel Blockers
Anticonvulsants; Breast neoplasms; Colonic neoplasms; Prostatic neoplasms; Sodium channels