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Hand-Foot and Stump Syndrome to Sorafenib

Department of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, IL

Timothy Kuzel

Division of Hematology/Oncology, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL

Mario E. Lacouture

Skin and Eye Reactions to Inhibitors of EGFR and Kinases (SERIES) Clinic and Cancer Skin Care Program, Robert H. Lurie Comprehensive Cancer Center and Department of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, IL

A 47-year-old white man, who had an above-the-knee amputation of his left leg, was treated with single-agent sorafenib 400 mg orally twice daily for metastatic renal cell carcinoma. The patient regularly wore a prosthesis that encases his left stump. After approximately 8 weeks on sorafenib, the patient developed a tingling sensation of bilateral hands, his right sole, and his left stump. These quickly progressed to well-demarcated, tender, erythematous, scaling lesions on his palms, right sole (Fig 1) and left stump (Fig 2). Painless distal subungual splinter hemorrhages were also seen in all of his fingernails. Based on clinical findings and history, a diagnosis of hand-foot and stump syndrome (HFSS) secondary to sorafenib therapy was made.

View larger version (51K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 1.

View larger version (46K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2.

Other cutaneous adverse effects that can be caused by sorafenib warrant attention, including a seborrheic dermatitis-like rash, alopecia, stomatitis, splinter hemorrhages, and inflammation of actinic keratoses.⁵ The splinter hemorrhages may possibly be explained by the blockade of the vascular endothelial growth factor receptor, which might impair the intrinsic repair mechanisms of delicate injury-prone spiral capillaries.⁶ Depigmentation of terminal hairs has also been witnessed in clinical practice, occurring in as few as 8 weeks. In mice, blockade of c-kit signaling leads to complete but reversible hair depigmentation with inhibition of melanocyte proliferation and differentiation.⁷

Multitargeted tyrosine kinase inhibitors can induce a variety of dermatologic adverse events, which require early recognition and effective management,⁸ in order to ensure continued lifesaving antineoplastic therapy. It is anticipated that observations such as the one described here, will contribute to a better understanding and further investigations towards the optimization of multitargeted therapies.

Authors' Disclosures of Potential Conflicts of Interest

Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment: N/A Leadership: N/A Consultant: Mario E. Lacouture, Bayer Pharmaceuticals Stock: N/A Honoraria: N/A Research Funds: N/A Testimony: N/A

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