Amlodipine improves the outcomes of regorafenib in metastatic colorectal cancer

Abstract

Regorafenib is a multikinase inhibitor. It is used for metastatic colorectal cancer (mCRC) treatment. It has a mild effect. Regorafenib outcomes, and side effects may vary across patients. This study was aimed to evaluate the factors that affect regorafenib outcomes in mCRC patients. We conducted a single-center and retrospective study. Fifty-six patients were included. All patients had received regorafenib for mCRC. Some clinical and pathological factors and the effects of these factors on overall survival (OS), progression-free survival (PFS), and disease control rates (DCR) were analyzed. Concomitant amlodipine intake with regorafenib improved OS [14.26 vs. 6.97 months; 95% confidence interval, 4.04-20.84; P = 0.031] and DCR at 12th week (90% vs. 46%; P = 0.012). Hepatic metastasis was found as the poorest prognostic factor in both univariate and multivariate analyses. Patients who received chemotherapy after regorafenib had better OS. Good performance status was the strongest indicator of better OS. Patients taking amlodipine for arterial hypertension at the same time with regorafenib had numerically better OS and PFS and statistically better DCR. Amlodipine itself already has anticancer effects, and it has additive anticancer effects with regorafenib. The presence of hepatic metastases was found to be the most important prognostic factor for OS. There were not any predictive factors of side effects to regorafenib.

Anticancer Activity of Calcium Channel Blockers in Colon Cancer Cell Culture

“…Amlodipine has a special place among repuposed molecules in cancer treatment. In our previous retrospective studies, we have shown that especially regorafenib and amlodipine combination increases the effectiveness at colorectal cancer [2]. In out another study, we showed that amlodipine inproves outcomes of erlotinib in non-small cell lung cancer [3].…”

Drug Repurposing to Enhance Antitumor Response to PD-1/PD-L1 Immune Checkpoint Inhibitors

“…Recently, the CCB amlodipine (commonly used to treat arterial hypertension) was found to markedly enhance the therapeutic response to gemcitabine chemotherapy in pancreatic cancer, extending survival and reducing the risk of distant metastases [ 53 ]. In addition, the drug was found to enhance the response to the multikinase inhibitor regorafenib in patients with metastatic colorectal cancer [ 54 ]. Several in vitro/in vivo studies have revealed that amlodipine, lercanidipine, and other structurally related CCBs can exert an antiproliferative action toward cancer cells and/or promote the efficacy of different anticancer drugs [ 55 , 56 , 57 , 58 , 59 , 60 ].…”