Context. There is increased cyclooxygenase-2 (COX-2) expression in malignant thyroid nodules compared with non-neoplastic and benign thyroid tissue.

Objective. Evaluate the efficacy of celecoxib, a selective COX-2 inhibitor, in treating patients with progressive metastatic differentiated thyroid cancer (DTC) and explore the relationship of clinical response to tumor COX-2 expression with immunohistochemistry in a subset of patients.

Design. Prospective phase II trial with Fleming single-stage design powered at 80% with a 5% rejection error to detect >20% progression-free survival at 12 months.

Setting. Ambulatory patients from tertiary referral academic medical centers.

Patients. Patients with progressive metastatic DTC who had failed prior standard therapy.

Intervention. Celecoxib 400 mg orally twice a day for 12 months.

Main Outcome Measure. Progression-free survival at 12 months of treatment using RECIST criteria and/or serum thyroglobulin.

Results. Twenty-three of 32 patients experienced progressive disease or stopped therapy due to toxicity thus fulfilling the intent-to-treat study endpoint for celecoxib failure. One patient achieved partial response (PR) and one patient completed 12 months of therapy progression-free. The patient with PR was on therapy along with 7 other patients when the study was terminated.

Conclusions. Celecoxib 400 mg orally twice per day fails to halt progressive metastatic DTC in most patients.