Regorafenib-induced hyperammonemic encephalopathy

J Clin Pharm Ther. 2014 Aug;39(4):446-8. doi: 10.1111/jcpt.12160. Epub 2014 Apr 7.

Abstract

What is known and objective: Regorafenib improves progression-free survival as a late-line treatment for patients with metastatic gastrointestinal stromal tumour (GIST). As a multitargeted tyrosine kinase inhibitor (TKI), the expected adverse events of regorafenib are similar to those reported with imatinib, sunitinib or sorafenib. We report the first case of hyperammonemic encephalopathy related to regorafenib in a patient with metastatic GIST.

Case summary: A 61-year-old man maintained on regorafenib for metastatic GIST presented with acute confusion. Discontinuation of regorafenib led to complete resolution of confusion, which later recurred with hyperammonemia on recommencing regorafenib. Cessation of regorafenib and normalization of hyperammonemia then resulted in resolution of confusion.

What is new and conclusions: Regorafenib withdrawal and recommencement had influenced the confusional state and hyperammonemia in this patient. There is a probable relationship between regorafenib and metabolic encephalopathy. There are case reports of similar encephalopathy thought to be induced by other multitargeted TKI, and, as such, a class effect could be postulated.

Keywords: adverse drug reactions; biological therapy; gastrointestinal stromal tumours; hepatic encephalopathy.

Publication types

  • Case Reports

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Agents / therapeutic use
  • Brain Diseases / chemically induced*
  • Brain Diseases / physiopathology
  • Gastrointestinal Stromal Tumors / drug therapy
  • Gastrointestinal Stromal Tumors / pathology
  • Humans
  • Hyperammonemia / chemically induced*
  • Hyperammonemia / physiopathology
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Phenylurea Compounds / adverse effects*
  • Phenylurea Compounds / therapeutic use
  • Pyridines / adverse effects*
  • Pyridines / therapeutic use

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Pyridines
  • regorafenib