Phase I clinical trial of nasopharyngeal radiotherapy and concurrent celecoxib for patients with locoregionally advanced nasopharyngeal carcinoma.

We evaluated the incidence of acute toxicity of concurrent cyclooxygenase-2 inhibitor (celecoxib) plus radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Thirty-four patients received an accumulated radiation dose of 72-76Gy in 36-38 fractions to the primary lesion and 60Gy in 30 fractions to cervical lymph-node lesions. Palpable residual nodes were boosted to 70Gy at the 90% isodose level with an electron field. Celecoxib was administered at escalating doses of 400, 600, and 800mg/day, starting 3days before the first fraction of radiotherapy and continuing throughout the course of radiotherapy. The majority of toxicities were grade 1, with mucositis and weight loss most frequently observed (28 of 34, 82.4%), followed by dermatitis (27 of 34, 79.4%) and otitis (14 of 34, 41.2%). The toxicities were not related to celecoxib dose (all P>0.05). Stomach pain was considered related to celecoxib, which developed in 2 patients at doses of 400mg and 800mg/day. No grade-3 or -4 toxicities or episodes of toxic death occurred. The tumors in 31 patients (31/34, 91.2%) showed a complete response, and 3 patients (3/34, 8.8%) had partial responses. The actuarial local progression-free survival was 96.6% at 1year, and the 2year overall survival rate was 84.6%. Celecoxib can be safely administered concurrently with nasopharyngeal radiotherapy at doses up to 800mg/day. The tumors responded well to treatment warranting further assessment in a phase II trial.