Fatal Liver Failure in a Patient Treated With Sunitinib for Renal Cell Carcinoma

Impaired clearance of sunitinib leads to metabolic disorders and hepatotoxicity

“…Although the clinical dose of sunitinib (50–150 mg·day −1 ) is not too high, sunitinib is given to patients continuously for several months, which might cause accumulation of sunitinib and its reactive metabolites. This might explain why sunitinib does not induce liver injury after the first round of use, with liver injury typically occuring during later cycles of sunitinib (Guillen et al, ; Mermershtain et al, ; Mueller et al, ; Taran et al, ; Weise et al, ).…”

“…A population‐based cohort study also found that severe liver injury occurred infrequently during exposure to sunitinib: 7.4–9.3% patients had doubled alanine transaminase (ALT) elevation; 8.6–18.1% patients had elevated bilirubin (Shantakumar et al, ). Furthermore, many clinical cases were reported on liver failure following sunitinib administration (Guillen, Meijer, & de Jongh, ; Mermershtain, Lazarev, Shani‐Shrem, & Ariad, ; Mueller, Rockey, & Rashkin, ; Taran, Ignatov, Smith, Costa, & Bischoff, ; Weise, Liu, & Shields, ). Recent studies reported that mitochondrial damage, inhibition of glycolysis, and metabolic activation contributed to sunitinib hepatotoxicity (Amaya et al, ; Paech, Bouitbir, & Krahenbuhl, ).…”

Lethal acute liver failure in a patient treated with sunitinib

“…We found four cases of liver failure in patients treated with sunitinib. Mermershtain et al 5 described a patient with acute liver failure during the first cycle of sunitinib for RCC. Another case report mentioned sunitinib-related acute liver failure in a woman with RCC during the fifth treatment cycle, which was reversible after discontinuation of the drug 6.…”

Multikinase inhibitor-induced liver injury in patients with cancer: A review for clinicians

“…DILI related to MKI use is hepatocellular (elevated aminotransferase levels with either no or a small increase in alkaline phosphatase levels), but cases of mixed DILI (elevation of both aminotransferase and alkaline phosphatase levels) have been published for dasatinib [56], imatinib [62], pazopanib [63], sorafenib [52], everolimus [64], and vemurafenib [65]. Elevated bilirubin levels meeting Hy's law criteria (hepatocellular type injury seen concurrently with bilirubin > 2X ULN) has been reported for crizotinib (2 cases -death) [35,66] [61,81], and the vemurafenib-ipilimumab association (2 casesrecovery) [48] (Table 2).…”

“…Glucocorticoids (20-40 mg/day) were necessary in addition to drug discontinuation in case reports of DILI related to imatinib [74], pazopanib [103], and the vemurafenib-ipilimumab combination [48]. Nevertheless, a fatal evolution despite drug withdrawal was reported for crizotinib [35,66], erlotinib [49,50,67,68], imatinib [58,72], pazopanib [63], regorafenib [46,77], sorafenib [80], and sunitinib [61,81,105]. Two cases of cirrhosis were reported after 18 and 24 months of imatinib treatment [74,106].…”