Acute Pancreatitis Secondary to Sorafenib Use

Abstract

Introduction: Sorafenib is indicated for the treatment of advanced renal cell carcinoma and unresectable hepatocellular carcinoma. Case Report: A 68-year-old male with metastatic renal cell carcinoma was started on sorafenib 200 mg orally bid. He presented to the ER 11 days afterward with severe epigastric pain radiating to the back. Serum amylase and lipase on admission were 148 U/L and 805 U/L, respectively. Abdominal CT revealed microlithiasis without evidence of cholecystitis, this was unchanged from imaging done a couple of months ago; there was no abnormality of the biliary and pancreatic ductal system. He had no history of alcohol abuse; serum triglyceride, calcium, and liver function tests were within normal limits. Sorafenib was discontinued upon admission, he was made NPO, IV fluids were started, and narcotics were administered as needed; there was complete symptom resolution within 48 hours. Sorafenib was re-started 7 days after admission at the same dose. During outpatient follow-up 3 weeks later, serum amylase and lipase were 50 and 99, respectively, and there was no recurrence of symptoms. He took sorafenib for a total of 10 weeks before voluntarily discontinuing it; he opted for hospice care. Discussion: Sorafenib is a small-molecule inhibitor that binds to serine/threonine Raf-1 kinase and multiple classes of receptor tyrosine kinases (RTKs), including vascular endothelial growth factor receptor (VEGFR)-2, VEGFR-3, platelet-derived growth factor receptor (PDGFR), Fms-like tyrosine kinase-3 (FLT-3), and c-kit. The VEGFR-2/PDGFR signaling cascade is involved in vasculogenesis, angiogenesis, tumor cell motility, and metastasis. The development of acute pancreatitis in patients on sorafenib may lie in the role of VEGF in the maintenance of adult pancreatic fenestrated capillaries and regulation of the cell cycle of the acinar cells; therefore, VEGF inhibition would lead to ischemia, acinar cell apoptosis, and release of autodigestive enzymes. In addition, sorafenib decreases GI motility, which in turn may cause reflux of duodenal contents into the pancreatic duct and induce the premature activation of zymogens within the pancreatic acinar cell, resulting in the release of active enzymes within pancreatic tissue, leading to autodigestion. Sorafenib may cause pancreatitis; patients initiating this medication should be made aware of this potential complication and monitored for it. Sorafenib should be interrupted in patients who develop pancreatitis, but may be re-started after carefully assessing the risks and benefits of treatment. If there's a recurrence of pancreatitis we recommend discontinuing the medication permanently.