A110: Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: a population-based study
1University of York, York, UK,2Hull York Medical School, York, UK
Metastasis is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) are present in cancer cells, where they regulate invasion and metastasis. VGSCs are inhibited by carbamazepine, lamotrigine, phenytoin and valproate. Several VGSC-inhibiting drugs reduce metastasis in murine cancer models. We aimed to test the hypothesis that patients on long-term VGSC-inhibiting drugs who developed cancer live longer than those not taking these drugs, benefiting from their anti-metastatic effects.
A cohort study was performed on primary care data from the QResearch database, including patients with breast, bowel or prostate cancer. Overall survival was used as a surrogate indicator of metastasis because metastasis is not reliably recorded in general practice data. 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 (95% CI 8·8 to 10·2) in the exposed group (n=5 440) and 18·4 years (95% CI 18·1 to 18·7) in the control group (n=87 825) (log-rank , p<0·001). Mortality was increased in the exposed group compared to the control group (hazard ratio 1·42, 95% CI 1·36 to 1·49, p<0·001). Sensitivity analyses considering level of exposure to the drugs, most commonly prescribed drug, and cancer type showed the results to be robust.
Contrary to the preclinical data, the overall survival of patients with breast, bowel and prostate cancer, who had been prescribed VGSC blockers prior to their cancer diagnosis, was significantly shorter than for patients not exposed to these drugs. However, we were unable to rule out confounding by indication, or determine cause of death. Further research is needed to investigate the relationship between VGSC-inhibiting drugs and cancer survival.