Background: Sunitinib is one of the most commonly used first line treatments for metastatic renal cell carcinoma (mRCC). While toxicities are common, rhabdomyolysis is rare. The case presented here describes the quick and severe nature of this toxicity.
Case: The patient is a 71-year-old white male with mRCC admitted on 3/29/17 due to muscle weakness, fatigue, poor oral intake, and difficulty swallowing for 2 weeks. He was diagnosed with RCC and had a right nephrectomy in 2014. He developed biopsy proven lung metastasis, and sunitinib was started in May 2016. Sunitinib dose at that time was 37.5 mg per oral daily x 4 weeks every 6 weeks. On admission, he had a platelet count of 13,000, serum creatinine 2.23 mg/dL, total bilirubin 4 mg/dL, AST/ALT > 2,000 U/L, INR 2.9, calcium 7.5, creatinine kinase > 5,000 U/L, uric acid 12 mg/dL, and severe global hypokinesia with LVEF 30-35%. He quickly developed lactic acidosis and ARDS. In ICU he received bicarbonate, oxygen, furosemide, and treatment for hyperkalemia. Despite all treatment support he continued to decline. His family chose to deescalate care, and he died on 4/1/17.
Discussion: Sunitinib induced rhabdomyolysis has been reported in 2 patients with metastatic RCC. The proposed mechanism suggests sunitinib could interfere with fatty acid b-oxidation and glycogenolysis. Under these conditions AMP-kinase activity usually acts as a rescue pathway. Sunitinib inhibits AMP-Kinase thus causing decline in intracellular ATP and elevation in myoplasmic Ca2+. Sufficient ATP supply by mitochondrial respiratory chain fails and extrusion of Ca2+ to the extracellular space is reduced. Long-lasting Ca2+ elevations leads to myoplasmic Ca2+ overload and activate calpain proteases. The skeletal muscle specific calpain 3 protease may cause destruction of the myofibrils. Increase in creatinine kinase is the main clinical presentation.
Conclusions: Sunitinib-induced rhabdomyolysis is a very rare occurrence. Our case will be the third reported case in literature. Initial recognition of this toxicity is very important to ensure timely care.
References: (1) Ruggeri EM, Cecere FL, Moscetti L, Doni L, Padalino D, Di Costanzo F. Severe rhabdomyolysis during sunitinib treatment of metastatic renal cell carcinoma. A report of two cases. Ann Oncol. 2010;21(9):1926-1927. (2) Hohenegger M. Drug induced rhabdomyolysis. Curr Opin Pharmacol. 2012;12(3):335-339.
