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Research article:

Exposure to sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the QResearch primary care database


Caroline Fairhurst, Ian Watt, Fabiola Martin, Martin Bland, and William J. Brackenbury(2014) Exposure to sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the QResearch primary care database. BMJ Open, doi:

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Introduction: Metastasis from solid tumours is associated with significant morbidity and mortality, and is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) are drug targets for the treatment of epilepsy. VGSCs are also present in cancer cells, where they regulate metastatic cell behaviours, including cellular movement and invasion. Treating cancer cells with the VGSC-inhibiting anticonvulsant phenytoin reduces cellular invasion and migration. Together, these suggest that VGSCs may be useful targets for inhibiting metastasis. The purpose of this study is to test the hypothesis that use of VGSC-inhibiting drugs will reduce metastasis, and therefore increase survival time in cancer patients. Methods and analysis: A cohort study based on primary care data from the QResearch database will include patients with one of three common tumours: breast, bowel, and prostate. The primary outcome will be overall survival from date of cancer diagnosis. Cox proportional hazards regression will be used to compare the survival of cancer patients taking VGSC-inhibiting drugs (including anticonvulsants and Class I antiarrhythmic agents) with cancer patients not exposed to these drugs, adjusting for age and sex. Exposure to VGSC-inhibiting drugs will be defined as having at least one prescription for these drugs prior to cancer diagnosis. High and low exposure groups will be identified based on length of use. A number of sensitivity and secondary analyses will be conducted. Ethics and dissemination: The protocol has been independently peer-reviewed and approved by the QResearch Scientific Board. The project has also been approved by the University of York Ethical Review Process. The results will be presented at international conferences and published in an open access peer-reviewed journal, in accordance with the STROBE criteria.
Author for correspondence
William J. Brackenbury
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Res17: Breast cancer Download this codelist
Res17: Colorectal cancer Download this codelist
Res17: Prostate cancer Download this codelist
Res17: Alcohol status Download this codelist
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Res17: Metastases Download this codelist
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