Sorafenib-Induced Bilateral Osteonecrosis of Femoral Heads

A 53-year-old man diagnosed with hepatocellular carcinoma(HCC) occurring in post–hepatitic C cirrhosis was first treated withright hepatectomy in May 2004. Because of cytologically proven re-currence as mediastinal and vertebral metastases, he was treated withchemotherapycombininggemcitabineandoxaliplatinefromDecem-ber 2004 to January 2005. The bone lesions extended and becamepainful, so the patient received analgesic lombar radiotherapy in Sep-tember 2005 and cimentoplasty in September 2007. In addition, sor-afenib (Nexavar; Bayer Pharmaceuticals Group, Montville, NJ) at adosage of 800 mg per day was started in February 2008. Initial serumlevel of alpha fetoprotein (AFP) was 180 ng/mL. Ten months afterstarting the treatment, the patient suffered from hip pain when walk-ing. Physical examination was normal except for pain on active andpassive leg mobilization. Blood tests were unremarkable, except forhepaticcytolysisrelatedtoongoinghepatitisC.TheserumlevelofAFPwas 600 ng/mL. Magnetic resonance imaging of the femoral headsshowedbilateralosteonecrosis(Fig1);asubchondrallineofdemarca-tion bounded a low signal intensity on T1- and T2-weighted images,corresponding to the necrotic area. There were bone marrow edemaand subchondral fissures. The patient did not receive (at that time orpreviously)corticosteroidorbiphosphonatetreatment.Sorafenibwasstopped and we declared this adverse event to the pharmacovigilancecenter of Lyon, France, in February 2009 (number LY20090440).SorafenibisanoralmultikinaseinhibitorthatinhibitsRafserine/threonine kinases and tyrosine kinase receptors involved in tumorgrowth and angiogenesis. It has demonstrated preclinical and clin-ical activity in several tumor types, including advanced HCC.