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Reversible Hepatic Cytolysis Secondary to Sunitinib in Metastatic Renal Carcinoma

Abstract

Omar El Mesbahi and Fatima Zahra El M’rabet

Liver damage is further characterized into hepatocellular (predominantly initial Alanine transferase elevation) and cholestatic (initial alkaline phosphatase rise) types. However they are not mutually exclusive and mixed type of injuries are often encountered. Serious drug-induced hepatotoxicity is an infrequent but life-threatening complication often identified through post marketing drug safety surveillance. The main toxicities of Tyrosine Kinase Inhibitors (TKI) therapy are fatigue, rash, diarrhea, hypertension, stomatitis, hand-foot syndrome, hypothyroidism and cardiac toxicity. Whilst most multitargeted TKI exhibit most of the side-effects noted above, each TKI has its particular profile. Sunitinib is an oral multikinase inhibitor that blocks the activity of VEGFR-2 and PDGFR, as well as Src, Abl, insulin-like growth factor receptor-1 and fibroblast growth factor receptor-1 tyrosine kinases, approved by the United States Food and Drug Administration (FDA) in January 2006 for treatment of renal cell carcinoma and gastrointestinal stromal tumor after disease progression or intolerance of Imatinib mesylate. In preapproval clinical trials, two patients reportedly experienced hepatotoxicity during treatment with sunitinib. Although both patients had evidence of liver metastasis before receiving sunitinib, the FDA deemed the suggestion of hepatotoxicity equivocal. We report the case of a patient treated for metastatic renal carcinoma who presented a hepatic cytolysis after introduction the sunitinib: 50mg/day, this is a second report case in the English literature in our knowledge. Clinicians should be aware of this possible adverse effect of sunitinib, and continued pharmacovigilance is imperative to accurately quantify the possible risk of sunitinib-related hepatotoxicity.