Cancers often spread to distant sites in the body. This process is called metastasis and is regulated by sodium channels located in the membranes of cancer cells. Sodium channels are also found in the nervous system, and drugs used that block these channels are used in the treatment of epilepsy. One such drug, phenytoin, has been found to reduce metastasis in mice, suggesting that anti-epileptic drugs may have a role in treating cancer. However, in previous research we found that patients taking similar drugs were less likely to survive following a diagnosis of cancer, possibly because they also had epilepsy. We now wish to use a richer dataset to study the relationships between epilepsy, cancer, sodium channel blocking drugs and survival in more detail, including examining specific causes of death. If successful, this would facilitate clinical trials of sodium channel blocking drugs for patients with breast cancer.
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 cancer patients, but we were unable to control for cause of death or indication for prescription. The purpose of the present study is to interrogate a different database in order to further investigate the relationship between VGSC-inhibiting drugs and cancer-specific survival. A cohort study using primary care data from the CPRD database will include patients with diagnosis of breast, bowel and prostate cancer. The primary outcome will be cancer-specific survival from 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 cancer patients 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 protocol has been peer reviewed and published.
Cancer-specific survival; overall survival, cancer-specific outcome (e.g. hospital admission, treatment).
William Brackenbury - Chief Investigator - University of York
Tim Doran - Corresponding Applicant - University of York
Caroline Fairhurst - Collaborator - University of York
Ian Watt - Collaborator - University of York
Martin Bland - Collaborator - University of York
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation