Ohtaki_2026_Anticancer.Res_46_359

BACKGROUND/AIM: Regorafenib, a multikinase inhibitor widely used to treat metastatic colorectal cancer (mCRC), is associated with elevations in pancreatic enzyme levels. However, clinical predictors of this adverse event have yet to be adequately defined. This study aimed to identify risk factors for regorafenib-induced enzyme elevation in routine clinical practice. PATIENTS AND METHODS: We retrospectively evaluated 47 patients with mCRC who received regorafenib between May 2013 and October 2024. Pancreatic enzyme elevation was defined as a Common Terminology Criteria for Adverse Events (CTCAE) grade <=1 increase in serum lipase or amylase levels within 28 days of treatment initiation. Clinical data were extracted from medical records, and risk factors were assessed using univariate and multivariate logistic regression. Sensitivity analyses were performed to confirm the robustness of the findings. RESULTS: Lipase elevation occurred in 48.9% of patients, whereas amylase elevation was observed in 8.5% of patients. Severe enzyme elevation (CTCAE grade <=3) was detected in 17.0% and exclusively involved lipase. The median onset time was 7 days, with no cases of acute pancreatitis reported. Multivariate analysis identified prior anti-vascular endothelial growth factor (VEGF) therapy lasting <=300 days as an independent risk factor (adjusted odds ratio 5.99, 95% confidence interval 1.49-31.41, p=0.01). Sensitivity analyses supported this association. CONCLUSION: The elevation of pancreatic enzymes, predominantly lipase, is a frequent early adverse event associated with regorafenib treatment. A history of prolonged anti-VEGF therapy may predispose patients to toxicity, highlighting the need for close monitoring during the initial treatment phase. These findings provide novel insights that may help to optimize the safe clinical use of regorafenib.