A case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma
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- Tsuji, K., Takemura, K., Minami, K. et al. Clin J Gastroenterol (2013) 6: 255. doi:10.1007/s12328-013-0381-2
We report on a case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma. A 70-year-old man was admitted to our hospital with fatigue, myalgia and an elevated creatine phosphokinase level. He was diagnosed as rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma. After discontinuation of sorafenib, his fatigue and myalgia resolved and his creatine phosphokinase level returned to normal. Rhabdomyolysis related to sorafenib treatment is rare adverse effect. This is the first detailed case report of rhabdomyolysis related to sorafenib treatment.
KeywordsRhabdomyolysis Sorafenib Adverse effect
Sorafenib is a small molecule that inhibits multiple kinases involved in angiogenesis and tumor growth [1, 2]. The efficacy of sorafenib for the treatment of advanced hepatocellular carcinoma (HCC) has been demonstrated in phase III randomized trials [3, 4], and sorafenib is now standard treatment for advanced HCC. The major adverse effects of sorafenib include skin rash, hand−foot skin reactions, diarrhea and hypertension.
Rhabdomyolysis related to sorafenib treatment has been identified during post-approval use of sorafenib. It is rare adverse effect. To our knowledge, there are no detailed case reports regarding rhabdomyolysis related to sorafenib treatment. Rhabdomyolysis is characterized by leakage of myoglobin and other intracellular proteins and electrolytes into the circulation, and may be associated with various diseases, injuries, medications and toxins . Early recognition of drug-induced rhabdomyolysis is important for successful management . Here, we report a case of rhabdomyolysis in a patient with advanced HCC who was taking sorafenib.
At the start of treatment
WBC (per μL)
Platelets (per μL)
11.4 × 104
3.5 × 104
Prothrombin time (%)
Total bilirubin (mg/dL)
Serum myoglobin (ng/mL)
Urine myoglobin (ng/mL)
The patient’s family history was unremarkable. He had no personal history of smoking or alcohol abuse. In addition to sorafenib (800 mg/day) for the past 12 days, he was taking magnesium oxide, bifidobacterium, sulpiride, ursodeoxycholic acid and alprazolam. For several years there had been no change to his drugs except for sorafenib.
This is the first case report of rhabdomyolysis related to sorafenib treatment. Sorafenib is an orally active multikinase inhibitor which has been approved for the treatment of advanced HCC and advanced renal cell carcinoma by the US Food and Drug Administration. Pivotal phase III randomized trials showed an overall survival benefit with sorafenib treatment, and established its efficacy and safety for the treatment of advanced HCC and advanced renal cell carcinoma [3, 4, 7, 8].
Rhabdomyolysis related to sorafenib treatment is rare. Rhabdomyolysis has been reported during post-approval use of sorafenib. Although there are no detailed reports regarding rhabdomyolysis related to sorafenib treatment for advanced HCC, nine cases have been reported to the enterprise up to March 2013 in Japan . As rhabdomyolysis was reported voluntarily from a population of uncertain size, the frequency of this adverse effect remains unclear.
The mechanism of rhabdomyolysis related to sorafenib treatment is not clear. Antoun et al.  reported statistically significant weight loss in patients taking sorafenib, which was associated with a significant reduction in skeletal muscle mass. Although the mechanism of this muscle loss is unclear, they suggested that kinases might play an important role in the regulation of muscle protein synthesis .
Rhabdomyolysis has been described in patients treated with the tyrosine kinase inhibitors imatinib and sunitinib [11, 12]. Two patients who developed severe rhabdomyolysis related to sunitinib treatment had a >50 % reduction in left ventricular ejection fraction . However, our patient had a normal ejection fraction. Sorafenib rarely causes a decrease in left ventricular ejection fraction , whereas sunitinib is known to cause decreased left ventricular ejection fraction. The inhibition of tyrosine kinase activity by sunitinib may accompany cardiac toxicity, but it is possible that this effect does not occur with sorafenib. Recurrence of rhabdomyolysis following reintroduction of sorafenib treatment has been reported in only one case up to March 2013; however, another case reported no recurrence of sorafenib-induced rhabdomyolysis after reintroduction of sorafenib treatment . Reintroduction of sorafenib treatment after drug-induced rhabdomyolysis may be dangerous, but there is currently no conclusive evidence for this.
We report a case of rhabdomyolysis related to sorafenib treatment. The therapeutic strategy for advanced HCC has not been definitively established; sorafenib treatment for advanced HCC improves survival, but median survival in Asian patients is less than that seen in Westerners [3, 4]. Intrahepatic arterial chemotherapy is often performed for intrahepatic advanced HCC in Japan. It has not yet been established whether sorafenib or chemotherapy treatment is superior for intrahepatic advanced HCC, and the results of an ongoing clinical trial are highly anticipated. In addition, since the survival benefit of intrahepatic arterial chemotherapy has not been demonstrated in randomized controlled studies, sorafenib treatment for advanced HCC seems appropriate at this time. It is important to note that rhabdomyolysis related to sorafenib treatment is a potentially life-threatening condition, and physicians need to consider the potential adverse effects of rhabdomyolysis in patients administered sorafenib.
Conflict of interest
The authors declare that they have no conflict of interest.
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