Development and management of severe cutaneous side effects in head-and-neck cancer patients during concurrent radiotherapy and cetuximab

Background: The concurrent administration of cetuximab to radiotherapy has recently been shown to improve the clinical outcome of head-and-neck cancer (HNC) patients. An aggravation of the radiation-induced skin toxicity was not described. Here, however, two cases with severe skin toxicity during the combined treatment are reported. Clinical Observations: In a small group of five patients with locally advanced HNC treated with irradiation and concurrent cetuximab, two cases of unusually severe radiation dermatitis were observed. Both patients developed confluent moist desquamations confined to the irradiation field at a dose of 40 Gy (CTC [Common Toxicity Criteria] grade 3), which progressed into an ulcerative dermatitis (grade 4) at 58 Gy and 46 Gy, respectively. Histopathology showed a vacuolic degeneration of basal keratinocytes, subepidermal blister formation, and mixed perivascular and interstitial inflammatory infiltrates leading to a complete loss of the epidermis. These cutaneous side effects led to the discontinuation of radiotherapy. Topical corticosteroids and systemic antibiotic treatment resulted in wound healing, which allowed the continuation of radiotherapy. Conclusion: These findings indicate that cetuximab may have the potential to enhance the severity of radiation dermatitis in HNC patients. A systematic monitoring of cutaneous side effects during radiotherapy plus cetuximab is advised in order to reliably estimate the frequency of severe (grade 3/4) radiation dermatitis.