January 2010 COMMUNITY ONCOLOGY 23 Volume 7/Number 1 Quality Care Commun Oncol 2010;7:23–29 © 2010 Elsevier Inc. All rights reserved. Practical considerations in the management of hand-foot skin reaction caused by multikinase inhibitors Laura S. Wood, RN, MSN, OCN, 1 Harvey Lemont, DPM, 2 Aminah Jatoi, MD, 3 Mario E. Lacouture, MD, 4 Caroline Robert, MD, 5 Karen Keating, RPT, MBA, 6 and Roger Anderson, PhD 7 1 Cleveland Clinic Taussig Cancer Institute, Cleveland, OH; 2 Temple University School of Podiatric Medicine, Philadelphia, PA; 3 Department of Oncology, Mayo Clinic Cancer Center, Rochester, MN; 4 Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY; 5 Service de Dermatologie, Institut Gustav Roussy, Villejuif, France; 6 Global Health Economics, Outcomes, and Reimbursement, Bayer Healthcare Pharmaceuticals, Montville, NJ; 7 Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA Multikinase inhibitors (MKIs, eg, sorafenib and sunitinib) are oral anticancer agents associated with hand- foot skin reaction (HFSR), a cutaneous adverse event affecting 20%–40% of patients treated with these drugs. Although usually mild, symptoms of HFSR can evolve into a painful condition, resulting in a shortened duration or intensity of cancer treatment. An international, interdisciplinary panel of experts recently provided the first consensus recommendations for the management of MKI-associated HFSR. Manuscript received July 15, 2009; accepted December 2, 2009. This study has been supported by an educational grant from Bayer Healthcare Pharmaceuticals, Montville, NJ. Correspondence to: Laura S. Wood, RN, MSN, OCN, Cleve- land Clinic Cancer Institute, 9500 Euclid Avenue R-33, Cleve- land, OH 44195; telephone: 216-444-9822; fax: 216-444-0114; e-mail: woodl@ccf.org C hemotherapeutic agents such as capecitabine (Xeloda) and doxoru- bicin have long been noted for their potential to cause skin toxicities that affect the hands and feet, vary- ing in occurrence and severity by agent and dos- ing schedule. 1–5 Novel oral targeted therapies with efficacy against advanced renal cell carcinoma, he- patocellular carcinoma, gastrointestinal stromal tu- mor, and other tumor types are now available. Some of the newer multikinase inhibitors (MKIs), such as sorafenib (Nexavar) and sunitinib (Sutent), are associated with the cutaneous toxicity known as hand-foot skin reaction (HFSR) in 20%–40% of treated patients, a distinct variant of the more wide- ly known hand-foot syndrome (HFS), or palmar plantar erythrodysesthesia (PPE), which occurs with older chemotherapies, such as capecitabine. 1–4 The recently approved kinase inhibitor pazopanib (Votrient) and others in clinical development, such as axitinib and cediranib, have also displayed HFSR toxicity. 6–8 When kinase inhibitors are used in combination with older chemotherapeutic agents, such as 5-flu- orouracil (5-FU), capecitabine, or doxorubicin, known to cause HFS, both HFSR and HFS may occur simultaneously, resulting in increased derma- tologic toxicity, thereby posing important challeng- es in patient management. Recently, a study found that the incidence and severity of HFSR were higher when sorafenib and bevacizumab (Avastin), an antivascular endothelial growth factor receptor (VEGF) antibody, were combined (31% for single- agent sorafenib vs 79% for the combination). 9 Presentation of MKI-associated HFSR MKI-associated HFSR is a clinically and patho- logically distinct skin toxicity from the HFS seen with older chemotherapeutic agents. 10 The appear- ance of HFSR usually presents as a mild to mod- erate cutaneous reaction, 5 developing within 2–4 weeks of starting treatment and with increasing cu- mulative MKI dose, 9–11 preceded or accompanied by paresthesias. 11,12 The National Cancer Institute (NCI) grading systems for dermatologic toxicities (NCI Common Terminology Criteria [CTC] v2.0 and CTC for Adverse Events [CTCAE] v3.0 and the recently released v4.0) are the most widely used methods of grading for HFSR and HFS. However, other modified grading systems that are more spe-