High Incidence of Oral Dysesthesias on a Trial of Gefitinib, Paclitaxel, and Concurrent External Beam Radiation for Locally Advanced Head and Neck Cancers

Objectives: To report a high incidence of oral mucosal dysesthesia Occurring in patients oil a pilot study of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa) in combination with paclitaxel (Taxol) and external beam radiation therapy for the treatment of locally advanced squamous cell carcinoma of the head and neck. Methods: Nine patients were enrolled on a pilot phase I trial of oral gefitinib 250 mg/d with 6 weekly doses of paclitaxel (36 or 45 mg/m(2)) and Concurrent radiation therapy [66-76 Gray (Gy)]. All had stage III/IVA-B squanious cell carcinoma of the head and neck. Patients were evaluated twice weekly by physicians and daily by nursing For adverse events. Results: Six of 9 patients (67%) developed a grade 3 "burning" quality oral dysesthesia. These patients received at least 50 Gy (range 50-70 Gy) to the oral tongue. The patients without grade 3 oral dysesthesia received less than 50 Gy radiation to the oral tongue. The oral dysesthesia was exacerbated by the ingestion of neutral pH liquids such as water. Of the 6 patients, all eventually developed common toxicity criteria grade 3/4 mucositis; however, symptoms continued after resolution of the mucositis. Gabapentin (Neurontin) was administered to 2 patients as a treatment for painftil mucosal neuropathy, Both patients had near resolution Of Symptoms despite the evolution of oral mucositis. Conclusions: Development of "burning"-type oral dysesthesia occurred in patients treated with the combination of gefitinib, paclitaxel, and external beam radiation of the oral tongue. This dysesthesia was improved by the use of gabapentin.