Regorafenib-induced hyperammonemic encephalopathy

Area of Science:

• Oncology
• Pharmacology
• Neurology

Background:

• Regorafenib is a multitargeted tyrosine kinase inhibitor (TKI) used for metastatic gastrointestinal stromal tumors (GIST).
• Expected adverse events of regorafenib are similar to other TKIs like imatinib, sunitinib, and sorafenib.
• Metastatic GIST treatment often involves late-line therapies such as regorafenib.

Observation:

• A 61-year-old male patient with metastatic GIST on regorafenib presented with acute confusion.
• Confusion resolved upon discontinuation of regorafenib.
• Confusion and hyperammonemia recurred upon re-initiation of regorafenib, resolving again after cessation.

Findings:

• This case demonstrates a probable relationship between regorafenib and metabolic encephalopathy.
• The patient experienced reversible hyperammonemic encephalopathy.
• Withdrawal and re-challenge with regorafenib correlated with the patient's confusional state and hyperammonemia.

Implications:

• Regorafenib may induce hyperammonemic encephalopathy, a potential adverse effect not previously reported.
• A class effect for metabolic encephalopathy among multitargeted TKIs may be postulated.
• Clinicians should consider monitoring for metabolic encephalopathy in patients treated with regorafenib or similar TKIs.