Antiepileptic drugs and metastasis
What is the aim of the study and why is it important?
Cancers often spread to distant sites in the body to form secondary tumours. This process is called metastasis. In order to metastasise, cancer cells need to invade through surrounding tissue. Metastasis is rarely curable. If we could slow the spread of cancer cells, we might be able to reduce metastasis. Sodium channels are drug targets for the treatment of epilepsy. Sodium channels are also present in cancer cells, where they regulate invasion. We have found that the antiepileptic drug phenytoin reduces invasion in preclinical models. Thus, sodium channels might be useful targets for inhibiting metastasis. We asked the question: do cancer patients who are taking antiepileptic drugs live longer than cancer patients not taking these drugs?
How is the research being done?
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.
Generic ethics approval reference
What were the main findings?
Surprisingly, we found that antiepileptic drugs associate with reduced survival in cancer patients.
Implications and Impact
We now need to know why the beneficial effect of these drugs seen in the lab is not reflected in the data from patients. One possible explanation that we are exploring is that most of the cancer patients taking these drugs will also have epilepsy and this might reduce their survival. In addition, the dose and timing of antiepileptic drugs may be important for them to have a beneficial effect in cancer patients.
This work was supported by the Medical Research Council [Fellowship G1000508] and the Wellcome Trust [ref: 097829] through the Centre for Chronic Diseases and Disorders (C2D2) at the University of York.
Caroline Fairhurst, Department of Health Sciences, University of York Ian Watt, Department of Health Sciences, University of York Fabiola Martin, Hull York Medical School and Department of Biology, University of York Martin Bland, Department of Health Sciences, University of York William Brackenbury, Department of Biology, University of York
Date research project approved
Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: a population-based study
Authors: Fairhurst C, Watt I, Martin F, et al.
Ref: Scientific Reports 2015;5:16758.
Exposure to sodium channel-inhibiting drugs and cancer survival: protocol for a cohort study using the QResearch primary care database
Authors: Fairhurst C, Watt I, Martin M, Bland M, Brackenbury WJ.
Ref: BMJ Open 2014; 4; e006604 doi: 10.1136/bmjopen-2014-006604