Phase II study of celecoxib in metastatic differentiated thyroid carcinoma

CONTEXT: There is increased cyclooxygenase-2 (COX-2) expression in malignant thyroid nodules compared with nonneoplastic and benign thyroid tissue. OBJECTIVE: The objective of the study was to evaluate the efficacy of celecoxib, a selective COX-2 inhibitor, in treating patients with progressive metastatic differentiated thyroid cancer (DTC) and to explore the relationship of clinical response to tumor COX-2 expression with immunohistochemistry in a subset of patients. DESIGN: The study was a prospective phase II trial with Fleming single-stage design powered at 80% with a 5% rejection error to detect more than 20% progression-free survival at 12 months. SETTING: Ambulatory patients were from tertiary referral academic medical centers. PATIENTS: Patients in the study had progressive metastatic DTC and had failed prior standard therapy. INTERVENTION: Patients were treated with celecoxib 400 mg orally twice a day for 12 months. MAIN OUTCOME MEASURE: The main outcome measure was progression-free survival at 12 months of treatment using Response Evaluation Criteria in Solid Tumors 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, and one patient completed 12 months of therapy progression-free. The patient with partial response was on therapy along with seven other patients when the study was terminated. CONCLUSIONS: Celecoxib 400 mg orally twice per day fails to halt progressive metastatic DTC in most patients.