Leg ulcers occurring under tyrosine kinase inhibitor therapy (sunitinib, nilotinib)

Certain anticancer drugs are known to induce leg ulcers, mainly chemotherapy agents such as hydroxyurea. We report 2 cases of leg ulcers in cancer patients treated with the tyrosine kinase inhibitors, sunitinib and nilotinib, and we discuss the role of these treatments in the pathogenesis of leg ulcers. Case 1. A 62-year-old patient on sunitinib for intrahepatic cholangiocarcinoma developed a lesion on her right foot. The vascular evaluation was negative. After progressive worsening, sunitinib was stopped and healing was observed within a few months. Case 2. A 83-year-old patient had been treated for chronic myeloid leukemia since 2005. Nilotinib was introduced in 2009. Peripheral arterial revascularization was required in May 2013. A few months later, worsening was noted with the onset of ulceration and necrosis of the third toe. Further revascularisation surgery was performed, and nilotinib was suspended and antiplatelets introduced. Healing occurred a few months later. Many skin reactions have been described in patients on nilotinib and sunitinib, but few publications report the development of de novo ulcers in patients without risk factors. The pathophysiology of the development of ulcers in patients receiving tyrosine kinase inhibitors is not clear, and probably involves several mechanisms of action. The increasing use of this type of treatment could lead to an upsurge in the incidence of vascular complications. We report two cases of leg ulcers developing in patients on tyrosine kinase inhibitors and raise the question of causal implication of these treatments in the pathogenesis of ulcers.