This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Peréz-Soler, R. Articles by Saltz, L. Search for Related Content PubMed PubMed Citation Articles by Peréz-Soler, R. Articles by Saltz, L. Social Bookmarking                            What's this?

Cutaneous Adverse Effects With HER1/EGFR-Targeted Agents: Is There a Silver Lining?

From the Department of Oncology, Montefiore Medical Center, Bronx, NY; and Gastrointestinal Oncology Service, Memorial Sloan-Kettering Cancer Center, New York, NY

Address reprint requests to Román Peréz-Soler, MD, Department of Oncology, Montefiore Medical Center, 111 E 210th St, Bronx, NY; e-mail: rperezso{at}montefiore.org

The human epidermal growth factor receptor (HER1/EGFR) is dysregulated in many solid tumors, making it an attractive target for anticancer therapy. A number of agents that target this receptor are in use or in development. A specific adverse effect common to this class of agent is a papulopustular rash, usually on the face and upper torso, which generally occurs in a dose-dependent manner. Little is known about the etiology of this rash, and there are no clear evidence-based management recommendations. Histologic data indicate that rash may be caused by HER1/EGFR inhibition in skin, although this has not been confirmed. Findings suggest that there is a relationship between the development of rash and response and/or survival, making rash a potential surrogate marker of activity. Data from multiple studies with cetuximab and erlotinib show a consistent relationship between rash and response, as well as between rash and survival. The relationship between rash and clinical outcome is currently less consistent for gefitinib. Some studies report a correlation, whereas others do not. The cause of the possible relationship between rash and clinical benefit remains unclear at this time, and additional studies are needed to determine the clinical utility of this observation.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Siena, A. Sartore-Bianchi, F. Di Nicolantonio, J. Balfour, and A. Bardelli Biomarkers Predicting Clinical Outcome of Epidermal Growth Factor Receptor-Targeted Therapy in Metastatic Colorectal Cancer J Natl Cancer Inst, October 7, 2009; 101(19): 1308 - 1324. [Abstract] [Full Text] [PDF]

				T. Bekaii-Saab, J. Markowitz, N. Prescott, W. Sadee, N. Heerema, L. Wei, Z. Dai, A. Papp, A. Campbell, K. Culler, et al. A Multi-Institutional Phase II Study of the Efficacy and Tolerability of Lapatinib in Patients with Advanced Hepatocellular Carcinomas Clin. Cancer Res., September 15, 2009; 15(18): 5895 - 5901. [Abstract] [Full Text] [PDF]

				A. J. Mutsaers, G. Francia, S. Man, C. R. Lee, J. M.L. Ebos, Y. Wu, L. Witte, S. Berry, M. Moore, and R. S. Kerbel Dose-Dependent Increases in Circulating TGF-{alpha} and Other EGFR Ligands Act As Pharmacodynamic Markers for Optimal Biological Dosing of Cetuximab and Are Tumor Independent Clin. Cancer Res., April 1, 2009; 15(7): 2397 - 2405. [Abstract] [Full Text] [PDF]

				S. Zheng, Y.-l. Pan, J.-l. Wang, K.-e. Huang, J.-h. Liu, J. Wang, and X.-q. Chen Gefitinib-induced hair alterations BMJ Case Reports, March 17, 2009; 2009(mar08_1): bcr0920080878 - bcr0920080878. [Abstract] [Full Text]

				H. C. Manning, N. B. Merchant, A. C. Foutch, J. M. Virostko, S. K. Wyatt, C. Shah, E. T. McKinley, J. Xie, N. J. Mutic, M. K. Washington, et al. Molecular Imaging of Therapeutic Response to Epidermal Growth Factor Receptor Blockade in Colorectal Cancer Clin. Cancer Res., November 15, 2008; 14(22): 7413 - 7422. [Abstract] [Full Text] [PDF]

				A. Jatoi and P. L. Nguyen Do Patients Die from Rashes from Epidermal Growth Factor Receptor Inhibitors? A Systematic Review to Help Counsel Patients About Holding Therapy Oncologist, November 1, 2008; 13(11): 1201 - 1204. [Abstract] [Full Text] [PDF]

				E. Eiling, M. Brandt, T. Schwarz, and A. Hauschild Pimecrolimus: A Novel Treatment for Cetuximab-Induced Papulopustular Eruption Arch Dermatol, September 1, 2008; 144(9): 1236 - 1238. [Full Text] [PDF]

				J. Autier, B. Escudier, J. Wechsler, A. Spatz, and C. Robert Prospective Study of the Cutaneous Adverse Effects of Sorafenib, a Novel Multikinase Inhibitor Arch Dermatol, July 1, 2008; 144(7): 886 - 892. [Abstract] [Full Text] [PDF]

				R. G. Pomerantz, R. E. Chirinos, L. D. Falo Jr, and L. J. Geskin Acitretin for Treatment of EGFR Inhibitor-Induced Cutaneous Toxic Effects Arch Dermatol, July 1, 2008; 144(7): 949 - 950. [Full Text] [PDF]

				M. R. Schneider, S. Werner, R. Paus, and E. Wolf Beyond Wavy Hairs: The Epidermal Growth Factor Receptor and Its Ligands in Skin Biology and Pathology Am. J. Pathol., July 1, 2008; 173(1): 14 - 24. [Abstract] [Full Text] [PDF]

				A. P. Brown, R. W. Dunstan, C. L. Courtney, K. A. Criswell, and M. J. Graziano Cutaneous Lesions in the Rat Following Administration of an Irreversible Inhibitor of erbB Receptors, Including the Epidermal Growth Factor Receptor Toxicol Pathol, April 1, 2008; 36(3): 410 - 419. [Abstract] [Full Text] [PDF]

				M. B. Toma and P. J. Medina Update on Targeted Therapy--Focus on Monoclonal Antibodies Journal of Pharmacy Practice, February 1, 2008; 21(1): 4 - 16. [Abstract] [PDF]

				V. Sans, T. Jouary, T. Hubiche, D. Smith, B. Milpied, and A. Taieb Baboon Syndrome Induced by Cetuximab Arch Dermatol, February 1, 2008; 144(2): 272 - 274. [Full Text] [PDF]

				M. Loprevite, M. Tiseo, M. Chiaramondia, M. Capelletti, C. Bozzetti, B. Bortesi, N. Naldi, R. Nizzoli, P. Dadati, A. Kunkl, et al. Buccal Mucosa Cells as In vivo Model to Evaluate Gefitinib Activity in Patients with Advanced Non Small Cell Lung Cancer Clin. Cancer Res., November 1, 2007; 13(21): 6518 - 6526. [Abstract] [Full Text] [PDF]

				B. H. O'Neil, R. Allen, D. R. Spigel, T. E. Stinchcombe, D. T. Moore, J. D. Berlin, and R. M. Goldberg High Incidence of Cetuximab-Related Infusion Reactions in Tennessee and North Carolina and the Association With Atopic History J. Clin. Oncol., August 20, 2007; 25(24): 3644 - 3648. [Abstract] [Full Text] [PDF]

				W. A. Messersmith and M. Hidalgo Panitumumab, a Monoclonal Anti Epidermal Growth Factor Receptor Antibody in Colorectal Cancer: Another One or the One? Clin. Cancer Res., August 15, 2007; 13(16): 4664 - 4666. [Full Text] [PDF]

				M. V. Karamouzis, J. R. Grandis, and A. Argiris Therapies Directed Against Epidermal Growth Factor Receptor in Aerodigestive Carcinomas JAMA, July 4, 2007; 298(1): 70 - 82. [Abstract] [Full Text] [PDF]

				B. Moy and P. E. Goss Lapatinib-Associated Toxicity and Practical Management Recommendations Oncologist, July 1, 2007; 12(7): 756 - 765. [Abstract] [Full Text] [PDF]

				C. Gridelli, M. A. Bareschino, C. Schettino, A. Rossi, P. Maione, and F. Ciardiello Erlotinib in Non-Small Cell Lung Cancer Treatment: Current Status and Future Development Oncologist, July 1, 2007; 12(7): 840 - 849. [Abstract] [Full Text] [PDF]

				M. E. Lacouture, C. Hwang, M. H. Marymont, and J. Patel Temporal Dependence of the Effect of Radiation on Erlotinib-Induced Skin Rash J. Clin. Oncol., May 20, 2007; 25(15): 2140 - 2140. [Full Text] [PDF]

				E. Van Cutsem, M. Peeters, S. Siena, Y. Humblet, A. Hendlisz, B. Neyns, J.-L. Canon, J.-L. Van Laethem, J. Maurel, G. Richardson, et al. Open-Label Phase III Trial of Panitumumab Plus Best Supportive Care Compared With Best Supportive Care Alone in Patients With Chemotherapy-Refractory Metastatic Colorectal Cancer J. Clin. Oncol., May 1, 2007; 25(13): 1658 - 1664. [Abstract] [Full Text] [PDF]

				P Bossi, C Liberatoscioli, C Bergamini, L. Locati, S Fava, G Rinaldi, E Orlandi, P Olmi, E Tagliabue, S Menard, et al. Previously irradiated areas spared from skin toxicity induced by cetuximab in six patients: implications for the administration of EGFR inhibitors in previously irradiated patients Ann. Onc., March 1, 2007; 18(3): 601 - 602. [Full Text] [PDF]

				P. M. Fracasso, H. Burris III, M. A. Arquette, R. Govindan, F. Gao, L. P. Wright, S. A. Goodner, F. A. Greco, S. F. Jones, N. Willcut, et al. A Phase 1 Escalating Single-Dose and Weekly Fixed-Dose Study of Cetuximab: Pharmacokinetic and Pharmacodynamic Rationale for Dosing Clin. Cancer Res., February 1, 2007; 13(3): 986 - 993. [Abstract] [Full Text] [PDF]

				B. Brandt, S. Meyer-Staeckling, H. Schmidt, K. Agelopoulos, and H. Buerger Mechanisms of egfr Gene Transcription Modulation: Relationship to Cancer Risk and Therapy Response Clin. Cancer Res., December 15, 2006; 12(24): 7252 - 7260. [Abstract] [Full Text] [PDF]

				A. Patnaik, D. Wood, A. W. Tolcher, M. Hamilton, J. I. Kreisberg, L. A. Hammond, G. Schwartz, M. Beeram, M. Hidalgo, M. M. Mita, et al. Phase I, Pharmacokinetic, and Biological Study of Erlotinib in Combination with Paclitaxel and Carboplatin in Patients with Advanced Solid Tumors Clin. Cancer Res., December 15, 2006; 12(24): 7406 - 7413. [Abstract] [Full Text] [PDF]

				J. Li, M. O. Karlsson, J. Brahmer, A. Spitz, M. Zhao, M. Hidalgo, and S. D. Baker CYP3A Phenotyping Approach to Predict Systemic Exposure to EGFR Tyrosine Kinase Inhibitors J Natl Cancer Inst, December 6, 2006; 98(23): 1714 - 1723. [Abstract] [Full Text] [PDF]

				G. Cusatis, V. Gregorc, J. Li, A. Spreafico, R. G. Ingersoll, J. Verweij, V. Ludovini, E. Villa, M. Hidalgo, A. Sparreboom, et al. Pharmacogenetics of ABCG2 and Adverse Reactions to Gefitinib J Natl Cancer Inst, December 6, 2006; 98(23): 1739 - 1742. [Abstract] [Full Text] [PDF]

				L. L. Garland, M. Hidalgo, D. S. Mendelson, D. P. Ryan, B. K. Arun, J. L. Lovalvo, I. A. Eiseman, S. C. Olson, P. F. Lenehan, and J. P. Eder A Phase I Clinical and Pharmacokinetic Study of Oral CI-1033 in Combination with Docetaxel in Patients with Advanced Solid Tumors. Clin. Cancer Res., July 15, 2006; 12(14): 4274 - 4282. [Abstract] [Full Text] [PDF]

				R. M. Sharkey and D. M. Goldenberg Targeted Therapy of Cancer: New Prospects for Antibodies and Immunoconjugates CA Cancer J Clin, July 1, 2006; 56(4): 226 - 243. [Abstract] [Full Text] [PDF]

				S. Goodin Erlotinib: optimizing therapy with predictors of response? Clin. Cancer Res., May 15, 2006; 12(10): 2961 - 2963. [Full Text] [PDF]