Calcium channel blockers are associated with improved survival in pancreatic cancer patients undergoing neoadjuvant chemotherapy and resection

BACKGROUND:Repurposing existing drugs for use in oncology is more efficient, cost-effective and safe than novel drug discovery. Calcium signalling is increasingly recognised to have a key role in chemoresistance. This study assessed the impact of calcium channel blockers (CCB) in pancreatic cancer. METHODS:Retrospective population study of patients undergoing resection (curative intent) of pancreatic ductal adenocarcinoma (SEER-Medicare, 2007-2017). Cox models were built to assess the impact on overall survival. As laboratory studies suggest a chemosensitising effect, the impact of CCB was assessed separately in patients receiving neoadjuvant chemotherapy. RESULTS:6,223 patients were included, of whom 660 were prescribed CCB. In total, 591 received neoadjuvant chemotherapy; in this cohort CCB prescription was associated with improved overall survival when adjusting for multiple prognostic factors (aHR = 0.715, 0.514-0.996, P = 0.047). This effect was not observed in patients not receiving neoadjuvant chemotherapy (aHR = 1.082, 0.982-1.191, P = 0.112). CONCLUSION:CCB prescription was associated with improved overall survival in patients receiving neoadjuvant chemotherapy prior to pancreatic cancer resection. The association was specific to the group of patients receiving neoadjuvant chemotherapy, mirroring the chemosensitising effect in laboratory studies. This defines patients receiving neoadjuvant chemotherapy as a target population for prospective clinical trials of CCB in pancreatic cancer.