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Array of cutaneous adverse effects associated with sorafenib

2009; Elsevier BV; Volume: 61; Issue: 2 Linguagem: Inglês

10.1016/j.jaad.2009.02.004

1097-6787

Heidi H. Kong, Maria L. Turner,

Colorectal Cancer Treatments and Studies

To the Editor: We read with interest the article by Robert et al1Robert C. Mateus C. Spatz A. Wechsler J. Escudier B. Dermatologic symptoms associated with the multikinase inhibitor sorafenib.J Am Acad Dermatol. 2009; 60: 299-305Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar in the February 2009 issue of the Journal. The frequency of sorafenib-associated dermatologic side effects and their impact on quality of life highlight the important role of dermatologists in caring for these patients. We wish to share our experience with oncology patients receiving sorafenib at the National Cancer Institute. We found skin changes similar to those described by the authors in addition to some not included in their report. Sixty-five patients on sorafenib therapy for solid tumors were evaluated in our dermatology clinic between August 2005 and December 2007. Twenty-four individuals were examined at baseline and followed for the development of dermatologic side effects (prospective cohort) and 41 individuals were examined after developing cutaneous lesions (consultation cohort). The cutaneous adverse effects discussed by the authors were similarly encountered in both of our cohorts: hand-foot skin reaction (HFSR; 63% prospective cohort and 78% consultation cohort, respectively), facial/scalp erythema/dysesthesias (63% and 68%), nail changes (33% and 32%), alopecia (21% and 39%), rash/exanthems (21% and 10%), cysts (8% and 27%), eruptive keratoacanthomas (4% and 7%), and eruptive nevi2Kong H.H. Sibaud V. Chanco Turner M.L. Fojo T. Hornyak T.J. Chevreau C. Sorafenib-induced eruptive melanocytic lesions.Arch Dermatol. 2008; 144: 820-822Crossref PubMed Scopus (71) Google Scholar (0% and 2%). In comparison with the review by Robert et al,1Robert C. Mateus C. Spatz A. Wechsler J. Escudier B. Dermatologic symptoms associated with the multikinase inhibitor sorafenib.J Am Acad Dermatol. 2009; 60: 299-305Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar our cohorts had a much higher incidence of HFSR.3Azad N.S. Aragon-Ching J.B. Dahut W.L. Gutierrez M. Figg W.D. Jain L. et al.Hand-foot skin reaction increases with cumulative sorafenib dose and with combination anti-VEGF therapy.Clin Cancer Res. 2009; 15: 1411-1416Crossref PubMed Scopus (127) Google Scholar Dermatologic adverse effects identified in our patients but not reported in Robert's review include the development of a generalized keratosis pilaris (KP)-like eruption (21% prospective cohort and 41% consultation cohort, respectively); stomatitis (17% and 22%), inflamed seborrheic keratoses (13% and 10%), and leukocytoclastic vasculitis4Chung N.M. Gutierrez M. Turner M.L. Leukocytoclastic vasculitis masquerading as hand-foot syndrome in a patient treated with sorafenib.Arch Dermatol. 2006; 142: 1510-1511PubMed Google Scholar (0% and 2%). The histology of the generalized KP-like eruption was typical for keratosis pilaris (Fig 1). The findings of a KP-like eruption, eruptive keratoacanthomas, and multiple cysts support the hypothesis that sorafenib causes alterations in the keratinocyte differentiation/proliferation pathways. While some of the exanthematous eruptions experienced by our patients clinically resembled erythema multiforme (EM), multiple biopsies revealed only mild superficial perivascular lymphocytic infiltrates with no evidence of basal vacuolization or necrotic keratinocytes as would be expected in EM. A previously reported patient, who presented with EM-like lesions, was demonstrated to have leukocytoclastic vasculitis on histologic examinaton. We recommend biopsies from these skin lesions for more precise diagnoses. Sorafenib was successfully reinitiated at reduced doses after temporary rest periods despite these eruptions. We concur with the assessments of Robert et al1Robert C. Mateus C. Spatz A. Wechsler J. Escudier B. Dermatologic symptoms associated with the multikinase inhibitor sorafenib.J Am Acad Dermatol. 2009; 60: 299-305Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar and Autier et al5Autier J. Escudier B. Wechsler J. Spatz A. Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor.Arch Dermatol. 2008; 144: 886-892Crossref PubMed Scopus (200) Google Scholar that the dermatologic side effects of sorafenib are often manageable with topical therapies and/or dose modifications. Increased awareness within the dermatologic community of the diversity, frequency, and treatment of sorafenib-induced cutaneous adverse reactions will be helpful to patients who require chronic therapy with this medication for their cancers. Dermatologic symptoms associated with the multikinase inhibitor sorafenibJournal of the American Academy of DermatologyVol. 60Issue 2PreviewThe multikinase inhibitor sorafenib (Nexavar) is associated with a relatively high incidence of dermatologic symptoms. Full-Text PDF