Article

Sunitinib-induced hyperammonemic encephalopathy in gastrointestinal stromal tumors.

Division of Hematology/Oncology, Research Institute of Clinical Medicine, Advanced Research Cancer Center, Chonbuk National University, Jeonbuk, South Korea.
Annals of Pharmacotherapy (impact factor: 2.13). 09/2011; 45(10):e56. DOI:10.1345/aph.1Q038 pp.e56
Source: PubMed

ABSTRACT To report 2 cases of hyperammonemic encephalopathy induced by sunitinib in patients with metastatic gastrointestinal stromal tumor (GIST).
A 58-year-old man with imatinib-resistant metastatic GIST presented to the emergency department with confusion that developed 17 days after the initiation of sunitinib 50 mg/day. His serum ammonia level was markedly elevated (210 μg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. His neurologic status normalized within 24 hours and his serum ammonia level decreased to 64 μg/dL. A 68-year-old woman with imatinib-resistant metastatic GIST was admitted into the emergency department with confusion and irritability that developed 10 days after the start of sunitinib therapy. Her serum ammonia level was markedly elevated (389 μg/dL). Sunitinib was discontinued, and an enema with lactulose was administered every hour. Within 24 hours, her mental status was improved and her serum ammonia level was decreased to 116 μg/dL. Sunitinib was reintroduced, and the same symptoms occurred after day 7 of administration. Sunitinib was not prescribed afterward and the woman did not experience any further encephalopathic symptoms.
Sunitinib is a small molecule that inhibits multiple receptor tyrosine kinases such as stem cell factor receptor, vascular endothelial growth factor, and platelet-derived growth factor. It is used as second-line therapy for patients with imatinib-resistant GIST. Hyperammonemic encephalopathy is an uncommon fatal complication of chemotherapy. According to the Naranjo probability scale, sunitinib was a probable cause of hyperammonemic encephalopathy in the patients described here. Although the mechanism of hyperammonemia is unclear, hyperammonemic encephalopathy might be caused by a vascular disorder related to the antiangiogenic properties of sunitinib, and it has ethnic differences associated with genetic polymorphisms.
Sunitinib may induce hyperammonemic encephalopathy in some patients. Although further studies are warranted, clinicians should be aware of this severe adverse event when using sunitinib for treatment of GIST.

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    [show abstract] [hide abstract]
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Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

58-year-old man
 
antiangiogenic properties
 
day 7
 
developed 10 days
 
developed 17 days
 
emergency department
 
hyperammonemic encephalopathy induced
 
imatinib-resistant GIST
 
imatinib-resistant metastatic GIST
 
inhibits multiple receptor tyrosine kinases
 
Naranjo probability scale
 
neurologic status normalized
 
probable cause
 
report 2 cases
 
second-line therapy
 
serum ammonia level
 
sunitinib 50 mg/day
 
sunitinib therapy
 
uncommon fatal complication
 
vascular endothelial growth factor
 

Na-Ri Lee