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Search for Evidence-Based Approaches for the Prevention and Palliation of Hand–Foot Skin Reaction (HFSR) Caused by the Multikinase Inhibitors (MKIs)

^aPenn State University College of Medicine, Hershey, Pennsylvania, USA; ^bMayo Clinic Cancer Center, Rochester Minnesota, USA; ^cInstitut Gustav Roussy, Villejuif, France; ^dCleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA; ^eBayer Healthcare Pharmaceuticals, Montville, New Jersey, USA; ^fRobert H. Lurie Comprehensive Cancer Center, Chicago, Illinois, USA

Key Words. Hand–foot skin reaction • Acral erythema • Palmar–plantar erythrodysesthesia • Multikinase inhibitors

Correspondence: Correspondence: Roger Anderson, Ph.D., A210 Public Health Sciences, Penn State University College of Medicine, 500 University Drive, Hershey, Pennsylvania, USA. Telephone: 717-531-2044; Fax: 717-531-4359; e-mail: randerso@hes.hmc.psu.edu

Received November 1, 2008; accepted for publication February 2, 2009.

Disclosures: Roger Anderson: Consultant/advisory role: Bayer Healthcare; Aminah Jatoi: None; Caroline Robert: Consultant/advisory role: Pfizer-Bayer; Laura S. Wood: Honoraria: Bayer, Onyx, Pfizer, Wyeth; Karen N. Keating: Employment/leadership position: Bayer Healthcare; Mario E. Lacouture: Consultant/advisory role: Bayer, Onyx; Research funding/contracted research: Bayer, Onyx. 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 independent peer reviewers.

Background. The anticancer multikinase inhibitors (MKIs) are associated with cutaneous adverse events, including hand–foot skin reaction (HFSR), a condition affecting 20%–40% of patients. Symptoms are usually mild, but can evolve into a painful condition that limits function and impacts quality of life (QoL), resulting in shortened cancer treatment duration or intensity. The goal of this study was to systematically review the literature on the prevention and palliation of MKI-associated HFSR, to identify areas for further clinical study, and to provide a foundation for evidence-based guidelines for HFSR management.

Methods. Systematic searches of the National Library of Medicine's PubMed database, Cochrane Reviews, BIOSIS, CancerLit, and the American Society of Clinical Oncology website were conducted using search terms for cutaneous toxicities associated with chemotherapeutic agents. Articles were categorized (C) based on type of agent and cutaneous reaction as: C1 (MKI and HFSR); C2 (MKI and other cutaneous toxicity); C3 (other antineoplastic agents and HFSR); and C4, other.

Results. Of the 2,069 abstracts screened, 350 (17%) met the criteria for C1–C4, with 56 (16%) coded as C1 with details of HFSR histology, pathogenesis, clinical outcome, QoL impact, and/or prevention and treatment approaches in MKI-treated patients. No randomized, controlled trials (RCTs) on prevention/palliation of HFSR were identified. Anecdotal evidence or expert opinion advocated protective measures, preventive and therapeutic skin care, systemic analgesics for pain, vitamin B₆, and MKI dose modification.

Conclusion. No articles containing evidence from RCTs on preventive/palliative approaches to MKI-associated HFSR have been published. Systematic study of optimal treatment strategies for HFSR is needed to advance development of evidence-based treatment guidelines.