Regorafenib-induced hyperammonemic encephalopathy

Kuo, James; Parakh, Sagun; Yip, Desmond

doi:10.1111/jcpt.12160

Cited by 15 publications

(12 citation statements)

References 16 publications

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“…[2,13–15] Among these, only 1 case of regorafenib-induced HE is described, [2] whereas the other have been related to sorafenib (1 case) and sunitinib (3 cases). [13,15] In 4 out of 5 patients, liver was involved as primary or metastatic site of disease; in all cases HE was developed after about 2 week after the start of TKI therapy and resolution of symptoms occurred mostly after 24 to 72 hours after stopping treatment and starting of antihyperammonemic therapy (Table 1).…”

Section: Discussionmentioning

confidence: 99%

“…Occurrence of liver toxicity was higher in the regorafenib than in the placebo group; the difference was attributable mainly to grade 1 or 2 events, but 1 fatal case of drug-induced liver injury was reported. Hyperammonemic encephalopathy (HE) related to regorafenib use has reported only in 1 patient with advanced GIST, [2] and it is a rare occurrence even with other TKIs. To our knowledge, this is the 1st case of HE under regorafenib treatment in a patient affected by mCRC with normal hepatic reserve.…”

Section: Introductionmentioning

confidence: 99%

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Unexpected side effect in mCRC

et al. 2017

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Rationale:Regorafenib represents a treatment option in heavily pretreated patients affected by metastatic colorectal cancer (mCRC). Its safety profile is typical of small-molecule tyrosine-kinase inhibitors (TKIs) and most adverse events are manageable.Patient concerns:A 56 years-old Caucasian man affected by mCRC with normal hepatic reserve was treated with regorafenib as second-line treatment. After only 2 days of therapy, the patient presented to the emergency department due to impairment of both spatial and temporal orientation and motor function with bradylalia.Interventions:Serum ammonia level was 191 mmol/L, liver function tests and complete blood count were normal. Regorafenib was withheld and branched chain amino acids and lactulose were administered.Outcomes:Serum ammonia level returned within the normal range, but when regorafenib was restarted at a lower dose level, a new episode of acute confusion arised.Main lesson:Discontinuation of regorafenib after confirmation of hyperammonemia is strongly recommended; reintroduction of the therapy at lower doses after resolution of symptoms related to hyperammonemic encephalopathy has to be discouraged.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Unexpected side effect in mCRC

et al. 2017

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“…There are four cases of sunitinib-induced hyperammonemic encephalopathy [10][11][12], one case of sorafenib-induced hyperammonemic encephalopathy [13], and one case of regorafenib-induced hyperammonemic encephalopathy [4] ( Table 1). The underlying mechanism of encephalopathy remains unclear, but in light of similar presentations, it can be reasonably suspected to be a result of a class effect of these TKIs [9].…”

Section: Discussionmentioning

confidence: 99%

“…Hyperammonemic encephalopathy is a life-threatening complication in patients with severe liver cirrhosis, and is often observed in liver dysfunction/failure cases. Regorafenib-induced hyperammonemic encephalopathy has been reported once in GIST, though it is a less common complication for CRC [4]. We first report two cases of hyperammonemic encephalopathy induced by regorafenib in patients with mCRC.…”

Section: Introductionmentioning

confidence: 88%

Regorafenib-Induced Hyperammonemic Encephalopathy in Metastatic Colon Cancer

Kitamoto¹,

Satake²,

Hatachi³

et al. 2015

JCPCR

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Regorafenib, a multi-targeted tyrosine kinase inhibitor (TKI), is used in metastatic colorectal cancer (mCRC) and gastrointestinal stromal tumors (GIST) for salvageline therapy. From clinical trials, the most commonly reported adverse events of regorafenib are hand-foot skin reactions, fatigue, diarrhea and hypertension. We report two cases of hyperammonemic encephalopathy induced by regorafenib in patients with mCRC. Hyperammonemic encephalopathy is a life-threatening complication in patients with severe liver cirrhosis, and is often observed in liver dysfunction/failure cases. Cases of hyperammonemic encephalopathy have been reported with various multi-targeted TKIs. The underlying mechanism of encephalopathy remains unclear, but in light of similar presentations, it can be reasonably suspected to be a result of a class effect of these TKIs. We suggest checking ammonia levels in patients on regorafenib presenting with altered consciousness, even if they have normal liver function. Discontinuation of regorafenib, as well as ammonia-lowering therapy, is essential to the management of this adverse effect, and recommencement of regorafenib should be discouraged.

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“…Steroids, commonly used for premedication or as part of chemotherapeutic regimens, can contribute to the development of HAE [20][21][22]. HAE has been reported with novel and more recently approved agents, such as tyrosine kinase inhibitors (TKIs), including sunitinib, sorafenib, and regorafenib [19,23,24]. There is no established management algorithm for cancer-or chemotherapy-related HAE.…”

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confidence: 99%

Hyperammonemic Encephalopathy Associated With Fibrolamellar Hepatocellular Carcinoma: Case Report, Literature Review, and Proposed Treatment Algorithm

et al. 2016

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We report a case of a 31-year-old man with metastatic fibrolamellar hepatocellular carcinoma (FLHCC) treated with gemcitabine and oxaliplatin complicated by hyperammonemic encephalopathy biochemically consistent with acquired ornithine transcarbamylase deficiency. Awareness of FLHCC-associated hyperammonemic encephalopathy and a pathophysiology-based management approach can optimize patient outcome and prevent serious complications. A discussion of the management, literature review, and proposed treatment algorithm of this rare metabolic complication are presented. The Oncologist 2016; 21:514-520Implications for Practice: Pathophysiology-guided management of cancer-associated hyperammonemic encephalopathy can improve patient outcome and prevent life-threatening complications. Community and academic oncologists should be aware of this serious metabolic complication of cancer and be familiar with its management.

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Regorafenib-induced hyperammonemic encephalopathy

Cited by 15 publications

References 16 publications

Unexpected side effect in mCRC

Unexpected side effect in mCRC

Regorafenib-Induced Hyperammonemic Encephalopathy in Metastatic Colon Cancer

Hyperammonemic Encephalopathy Associated With Fibrolamellar Hepatocellular Carcinoma: Case Report, Literature Review, and Proposed Treatment Algorithm

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