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First Published Online September 8, 2008
The Oncologist, Vol. 13, No. 9, 1001-1011, September 2008; doi:10.1634/theoncologist.2008-0131
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Symptom Management and Supportive Care

Evolving Strategies for the Management of Hand–Foot Skin Reaction Associated with the Multitargeted Kinase Inhibitors Sorafenib and Sunitinib

Mario E. Lacouturea, Shenhong Wub, Caroline Robertc, Michael B. Atkinsd, Heidi H. Konge, Joan Guitarta, Claus Garbef, Axel Hauschildg, Igor Puzanovh, Doru T. Alexandrescui, Roger T. Andersonj, Laura Woodk, Janice P. Dutcherl

aDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA; bDivision of Medical Oncology, Department of Medicine, Stony Brook University Cancer Center, Stony Brook, New York, USA; cDermatology Unit, Gustave-Roussy Institute, Villejuif, France; dDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA; eDermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA; fDepartment of Dermatology, Eberhard Karls University, Tübingen, Germany; gDepartment of Dermatology, University of Kiel, Kiel, Germany; hDivision of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA; iGeorgetown Dermatology, Washington, District of Columbia, USA; jPennsylvania State College of Medicine, Hershey, Pennsylvania, USA; kCleveland Clinic Taussig Cancer Center, Cleveland, Ohio, USA; lOur Lady of Mercy Medical Center, Comprehensive Cancer Center, New York Medical College, Bronx, New York, USA

Key Words. Sorafenib • Sunitinib • Hand–foot skin reaction • Forum consensus • Skin

Correspondence: Mario E. Lacouture, M.D., Department of Dermatology, Northwestern University Feinberg School of Medicine, 676 North St. Clair Street, Suite 1600, Chicago, Illinois 60611, USA. Telephone: 312-695-8106; Fax: 312-695-0537; e-mail: m-lacouture{at}northwestern.edu

Received June 11, 2008; accepted for publication July 30, 2008; first published online in THE ONCOLOGIST Express on September 8, 2008.

Disclosure: Employment/leadership position: None; Intellectual property rights/inventor/patent holder: None; Consultant/advisory role: Michael B. Atkins, Bayer/Onyx; Doru T. Alexandrescu, Bayer; Roger T. Anderson, Bayer; Claus Garbe, Bayer; Axel Hauschild, Bayer, Onyx; Janice P. Dutcher, Bayer/Onyx, Pfizer, Wyeth, Genentech; Mario E. Lacouture, Onyx, Bayer; Igor Puzanov, Spirogen; Caroline Robert, Bayer; Shenhong Wu, Onyx; Honoraria: Axel Hauschild, Bayer, Onyx; Laura Wood, Bayer/Onyx, Pfizer; Janice P. Dutcher, Bayer/Onyx, Pfizer, Wyeth, Novartis; Igor Puzanov, Pfizer, Novartis, Bayer; Shenhong Wu, Pfizer; Research funding/contracted research: Michael B. Atkins, Bayer/Onyx; Axel Hauschild, Bayer (Germany), Onyx (USA); Janice P. Dutcher, Bayer/Onyx, Pfizer, Wyeth, Genentech, Novartis; Mario E. Lacouture, Onyx; Ownership interest: None; Expert testimony: None; Other: None. The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the authors, planners, independent peer reviewers, or staff managers.

The multitargeted kinase inhibitors (MKIs) sorafenib and sunitinib have shown benefit in patients with renal cell carcinoma, hepatocellular carcinoma (sorafenib), and gastrointestinal stromal tumor (sunitinib). Their efficacy in other malignancies is currently being investigated because of their broad range of activity. The effectiveness of these drugs is somewhat diminished by the development of a variety of toxicities, most notably hand–foot skin reaction (HFSR). Although HFSR does not appear to directly affect survival, it can impact quality of life and lead to MKI dose modification or interruption, potentially limiting the antitumor effect. Currently, no standard guidelines exist for the prevention and management of MKI-associated HFSR. To address this issue, an international, interdisciplinary panel of experts gathered in January 2008 to discuss and evaluate the best-practice management of these reactions. Based on these proceedings, recommendations for the management of HFSR have been provided to offer patients the best possible quality of life while taking these drugs and to optimize the patient benefit associated with MKI therapy.




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