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Journal of Clinical Oncology, Vol 26, No 16 (June 1), 2008: pp. 2779-2780 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2007.15.7883
Fatal Toxic Epidermal Necrolysis Associated With Cetuximab in a Patient With Colon CancerDepartment of Dermatology, Chang Gung Memorial Hospital, Taipei, Taiwan
Linkou Burn Center, Department of Plastic Surgery, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan
Department of Dermatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan In August 2006, a 74-year-old man was admitted to our hospital for toxic epidermal necrolysis (TEN). He had been diagnosed with moderately differentiated adenocarcinoma of the proximal sigmoid colon, with hepatic metastases, in November 2004. He had received a regimen of bevacizimab 5 mg/kg, oxaliplatin 65 mg/m2, leucovorin 200 mg/m2, and fluorouracil 300 mg/m2 from November 2004 to October 2005. In March 2006, he received three cycles of irinotecan 125 mg/m2, leucovorin 20 mg/m2, and fluorouracil 500 mg/m2 treatment. There were no adverse reactions during the previous treatment course. Because of advanced hepatic metastases, he received additional cetuximab (250 mg/m2) weekly, from May 30 to July 19, 2006. Progressive paronychia and acneiform papules on the four limbs developed after the eighth course (mid-July). These cutaneous reactions continued to progress, turning into large blisters with extensive epidermal shedding on the trunk; he was sent to our emergency department on July 31. On physical examination, there were generalized confluent purpuric maculopapular lesions with blisters and large epidermal detachment. Severe oral ulcers were also present. Stevens-Johnson syndrome was diagnosed through clinical morphology.1 However, this case rapidly progressed to toxic epidermal necrolysis the next day (more than 70% epidermal detachment of the total body surface; Fig 1). Analysis of blister cells collected from skin lesions revealed a predominance of CD8+ cytotoxic T lymphocytes (83%) and natural killer cells (10%), which is in line with previous Stevens-Johnson syndrome/TEN studies.2 Serum antibodies for herpes simplex virus and Mycoplasma pneumoniae were all negative. Intravenous immunoglobulin 0.5 g/kg/d was prescribed for 4 days for his skin condition. Systemic antibiotics (imipenem and teicoplanin) were used for his complications of pneumonia (Staphylococcus aureus) and systemic fluconazole was also given for his cutaneous Candida albicans infection. However, acute renal and respiratory failure developed rapidly, and this patient died on August 13, 2006.
Cetuximab is a recombinant human and mouse chimeric monoclonal antibody that competitively inhibits the epidermal growth factor receptor (EGFR). It was the first antibody targeting EGFR approved by the US Food and Drug Administration for cancer therapy. Cetuximab monotherapy, with or without irinotecan, is increasingly used for metastatic colorectal cancer. Several types of adverse cutaneous reactions (such as acneiform skin reactions and periungual inflammation) to EGFR inhibitors have been reported. However, there is no documented fatal toxic epidermal necrolysis.3 The most common etiology of TEN is medication.1 Mucocutaneous TEN lesions usually develop 2 to 8 weeks after starting the culprit drug.1 Cytotoxic T lymphocytes are sensitized during this period. Although this is the first report of antibody-drug–induced TEN, a delayed allergic reaction associated with monoclonal antibody drug has been reported.4 Moreover, the underlying mechanism of EGFR inhibitors, which can enhance inflammatory responses and decrease survival of epithelial cells, may also contribute to the development of toxic epidermal necrolysis.5 To the best of our knowledge, this is the first case report of fatal TEN associated with cetuximab and anticancer agents. This report is all the more important because of the increasing use of cetuximab in patients with colorectal cancer. Clinical physicians should be aware of these possible complications so that early interventions can be made. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
REFERENCES 1. Heymann WR: Toxic epidermal necrolysis 2006. J Am Acad Dermatol 55:867-869, 2006[CrossRef][Medline] 2. Lacouture ME, Melosky BL: Cutaneous reactions to anticancer agents targeting the epidermal growth factor receptor: A dermatology-oncology perspective. Skin Therapy Letter 12:1-5, 2007[Medline] 3. Nassif A, Bensussan A, Boumsell L, et al: Toxic epidermal necrolysis: Effector cells are drug-specific cytotoxic T cells. J Allergy Clin Immunol 114:1209-1215, 2004[CrossRef][Medline] 4. Krumbholz M, Pellkofer H, Gold R, et al: Delayed allergic reaction to natalizumab associated with early formation of neutralizing antibodies. Arch Neurol 64:1331-1333, 2007 5. Lacouture ME: Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer 6:803-811, 2006[CrossRef][Medline]
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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