The Effect of Hand-Foot Skin Reaction Associated With the Multikinase Inhibitors Sorafenib and Sunitinib on Health-Related Quality of Life
November 2012 | Volume 11 | Issue 11 | Original Article | 61 | Copyright © November 2012
Beatrice Nardone MD PhD,a Jennifer R. Hensley MD,a Laura Kulik MD,b-e Dennis P. West PhD,a-e Mary Mulcahy MD,c-e Alfred Rademaker PhD,d,eMario E. Lacouture MDa,e,f
aDepartment of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL bDepartment of Medicine, Division of Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL cDepartment of Medicine, Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL dDepartment of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL eRobert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL fDermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY
Abstract
Introduction: The multikinase inhibitors sorafenib (SO) and sunitinib (SU) have shown benefit in a wide range of solid tumors. Although
these agents are generally well tolerated, they may be associated with dermatologic adverse events, particularly hand-foot
skin reaction (HFSR). The aim of this study is to evaluate the impact of HFSR associated with these multikinase inhibitors on patient
health-related quality of life (HRQOL).
Methods: Twenty-three patients with HFSR related to SO or SU were graded using the National Cancer Institute's Common Terminology
Criteria for Adverse Events (CTCAE) Version 3.0 for clinical severity and for impact on HRQOL through completion of the patient
self-administered Skindex-16 (SK-16). Clinical severity scores were compared to HRQOL assessments.
Results: Of the 23 patients with HFSR, clinical severity was grade 1 in 17.4%, grade 2 in 74%, and grade 3 in 8.6%. Median SK-16
scores were reported for symptoms (53.3), emotions (30.6), and functioning subscales (33.3). Median symptoms and emotions scores
positively correlated with HFSR clinical severity grade.
Conclusions: These findings demonstrate that HFSR related to SO or SU negatively impacts HRQOL, with the symptoms domain being
most significantly affected. In addition, CTCAE toxicity grading correlates with HRQOL.
J Drugs Dermatol. 2012;11(11)e61-e65.
INTRODUCTION
Sorafenib (SO) and sunitinib (SU) are small molecule inhibitors
with various targets that have shown benefits in
various malignancies, significantly improving progression-
free survival and overall survival, with reduced adverse
events (AEs) when compared with cytotoxic chemotherapy.1
Sunitinib malate is an oral multitargeted tyrosine kinase
inhibitor with antiangiogenic and antitumor activities. It is
currently approved for the treatment of advanced renal cell
carcinoma (RCC) and imatinib-resistant or imatinib-intolerant
gastrointestinal stromal tumor (GIST).2 Sorafenib tosylate is
also an orally active multikinase inhibitor (MKI) currently
approved for the treatment of advanced RCC3 and hepatocellular
carcinoma (HCC).4
Although targeted agents such as SO and SU are generally well
tolerated, they cause a variety of AEs that should be promptly
recognized for adequate clinical management.5 Cutaneous AEs
associated with SO and/or SU are noteworthy for their relatively
high frequency of occurrence: mucositis (up to 20% of patients),
rash (up to 40%), alopecia (up to 27%), xerosis (up to 16%), xerostomia
(up to 11%), and HFSR (up to 60%)6-9 (Figure 1).
One of the most clinically significant dermatologic AEs is HFSR, a
localized cutaneous reaction characterized by erythema, edema,
desquamation, pain, ulceration, or blistering, and affecting the bilateral
palms and/or soles, symptoms that usually present several
weeks after initiation of therapy.10 Although HFSR is not typically
considered to be life-threatening, it occurs in up to 60% (up to 9%
grade 3) of patients and can be painful, limiting daily activities.
Depending on clinical severity, HFSR requires interventions that
may include dose modification or discontinuation of treatment.9,11
Health-related quality of life (HRQOL) represents an important
outcome measure in clinical research and practice that is commonly
used to evaluate how illness can interfere with a person's
day-to-day life.12 Such a measure describes levels of physical,
social, and psychological well-being and assesses the burden
of disease on daily living. These instruments are widely used
in clinical trials to show how treatments for skin disease may
