A case of rhabdomyolysis related to sorafenib treatment for advanced hepatocellular carcinoma

A 70-year-old male was admitted to our hospital in August 2012. He had a 10-year history of hepatitis C virus infection, and had not received interferon therapy. In August 2011, computed tomography (CT) detected a small mass (about 1.8 × 1.6 cm) in the right lobe of the liver, which was diagnosed as HCC. In October 2011, he underwent partial resection of the liver for HCC. About three months later, CT revealed multiple masses in the liver, which were diagnosed as recurrent HCCs. In January and March 2012, he underwent transcatheter chemoembolization of the hepatic lesions. The drugs used for one of the cycles were epirubicin (20 mg) and lipiodol (3 mL). In June and July 2012, he received two cycles of intra-arterial infusion chemotherapy with cisplatin powder (IA-call) into the hepatic artery at a dose of 65 mg/m². Follow-up CT showed new metastatic lesions in the liver. He had Eastern Cooperative Oncology Group performance status 0 and Child-Pugh liver function class A (Table 1). Twelve days before admission he had started sorafenib therapy (400 mg twice a day); at this moment, 37 days had passed since the last intra-arterial infusion chemotherapy with IA-call. He was not taking any other new medications. No major adverse effects were observed during the first week of treatment. Although the skin rash and diarrhea did not appear, fatigue and myalgia appeared at 10 days after the onset of sorafenib treatment, and his symptoms gradually worsened.

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.

Physical examination revealed blood pressure 116/70 mmHg, heart rate 70 beats/min and body temperature 36.4 °C. He had proximal muscle weakness, but no other abnormality was observed. Laboratory testing showed increased serum creatine phosphokinase, myoglobin, aspartate aminotransferase and alanine aminotransferase levels, decreased platelet count, and increased urine myoglobin level (Table 1). Drug-induced rhabdomyolysis was suspected, and sorafenib was discontinued because the rhabdomyolysis had occurred within 2 weeks after the initiation of sorafenib treatment. The patient received infusion therapy (not including potassium) followed by a massive extracellular fluid infusion of >3 L per day for 2 days. After discontinuation of sorafenib and administration of intravenous fluids, his myalgia and fatigue resolved. Once his condition improved, the infusion volume was gradually reduced. Serum creatinine remained within normal limits throughout hospitalization, and renal failure was avoided. Creatinine phosphokinase levels returned to normal within one week (Fig. 1), i.e., compared to his laboratory test results upon admission which were similar to those seen in disseminated intravascular coagulation and severe liver damage. His condition improved rapidly with discontinuation of the sorafenib and administration of intravenous fluids only. There was no recurrence of rhabdomyolysis following reintroduction of other drugs except for sorafenib. He was discharged 20 days after hospitalization, with ongoing best supportive care for his HCC.