Dystrophic epidermolysis bullosa (EB) is a genetic skin fragility condition with propensity to skin cancer. The severest subtype is the generalized recessive dystrophic EB (RDEB), in which mechanically induced skin blisters and erosions heal with severe scarring. A common and potentially life-threatening complication in RDEB is cutaneous squamous cell carcinoma (SCC). In spite of generally good differentiation of SCC associated with RDEB (RDEB-SCC), the tumours behave in an aggressive manner and metastasize early. Despite the high prevalence of RDEB-SCC, systematic studies on therapeutic options have not been reported. Wide surgical excision is recommended, and unresectable cases have been treated with radiotherapy. Here we report the first treatment of metastasized RDEB-SCC with the epidermal growth factor receptor antagonist cetuximab (Erbitux®). The response was favourable, and adverse events were similar to those in patients without EB. Notably, no additional negative cutaneous effects, such as severer skin or mucosal blistering, occurred.

Keywords:
Epidermolysis bullosa dystrophica, Cetuximab, adverse reactions, Squamous cell carcinoma, Biological therapy
1.
Fine J, Eady RAJ, Bauer EA, Bauer JW, Bruckner-Tudermann L, Heagerty A, Hintner H, Hovnanian A, Jonkman MF, Leigh I, McGrath JA, Mellerio JE, Murrell DF, Shimizu H, Uitto J, Vahlquist A, Woodley D, Zambruno G: The classification of inherited epidermolysis bullosa (EB): report of the Third International Consensus Meeting on Diagnosis and Classification of EB. J Am Acad Dermatol 2008;58:931–950.
2.
Aumailley M, Has C, Tunggal L, Bruckner-Tuderman L: Molecular basis of inherited skin blistering disorders, and therapeutic implications. Expert Rev Mol Med 2006;8:1–21.
3.
Fine J, Johnson LB, Weiner M, Li K, Suchindran C: Epidermolysis bullosa and the risk of life-threatening cancers: the National EB Registry experience, 1986–2006. J Am Acad Dermatol 2009;60:203–211.
4.
Ortiz-Urda S, Garcia J, Green CL, Chen L, Lin Q, Veitch DP, Sakai LY, Lee H, Marinkovich MP, Khavari PA: Type VII collagen is required for Ras-driven human epidermal tumorigenesis. Science 2005;307:1773–1776.
5.
Pourreyron C, Cox G, Mao X, Volz A, Nuzhat B, Wong T, Fassihi H, Arita K, O’Toole EA, Ocampo-Candiani J, Chen M, Hart IR, Bruckner-Tuderman L, Salas-Alanis JC, McGrath JA, Leigh IM, South AP: Patients with recessive dystrophic epidermolysis bullosa develop squamous-cell carcinoma regardless of type VII collagen expression. J Invest Dermatol 2007;127:2438–2444.
6.
Bouali S, Chrétien AS, Ramacci C, Rouyer M, Becuwe P, Merlin JL: PTEN expression controls cellular response to cetuximab by mediating PI3K/AKT and RAS/RAF/MAPK downstream signalling in KRAS wild-type, hormone refractory prostate cancer cells. Oncol Rep 2009;21:731–735.
7.
Overman MJ, Hoff PM: EGFR-targeted therapies in colorectal cancer. Dis Colon Rectum 2007;50:1259–1270.
8.
Allegra CJ, Milburn Jessup J, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL: American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol 2009;27:1–6.
9.
Segaert S, Van Custem E: Clinical signs, pathophysiology and management of skin toxicity during therapy with epidermal growth factor receptor inhibitors. Ann Oncol 2005;16:1425–1433.
10.
Wacker B, Nagrani T, Weinberg J, Witt K, Clark G, Cagnoni PJ: Correlation between development of rash and efficacy in patients treated with the epidermal growth factor receptor tyrosine kinase inhibitor erlotinib in two large phase III studies. Clin Cancer Res 2007;13:3913–3921.
11.
Jatoi A, Rowland K, Sloan JA, Gross HM, Fishkin PA, Kahanic SP, Novotny PJ, Schaefer PL, Johnson DB, Tschetter LK, Loprinzi CL: Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes. Cancer 2008;113:847–853.
© 2009 S. Karger AG, Basel
2009
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.