Celecoxib fails against metastatic differentiated thyroid cancer development
Celecoxib does not halt the development of progressive metastatic differentiated thyroid cancer (DTC) in most patients, US scientists have found.
Manisha Shah, from the Ohio State University Medical Center in Columbus, and co-workers report their findings in the Journal of Clinical Endocrinology & Metabolism.
Explaining the background to their study, the team says that although DTCs are among the most curable cancers, patients with distant metastases have a survival rate of only about 50%. In addition, patients who do not respond to radioactive iodine therapy have worse prognoses. Thus the development of novel therapies for metastatic DTC "are desperately needed," they state.
The researchers hypothesized that the increased cyclooxygenase-2 (COX-2) expression in malignant thyroid nodules compared with non-neoplastic and benign thyroid tissue, may render the selective COX-2 inhibitor celecoxib to be of therapeutic use to patients with DTC.
To investigate this hypothesis, Shah et al evaluated the efficacy of celecoxib, a selective COX-2 inhibitor, in 32 patients with progressive metastatic DTC from tertiary referral academic medical centers. All had failed prior standard therapy.
Each participant received celecoxib 400 mg orally twice a day for 12 months.
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 revealed that 23 of the patients experienced a progression of their DTC or stopped celecoxib therapy due to toxicity, therefore fulfilling the intent-to-treat study endpoint for celecoxib failure.
One patient achieved partial response to therapy, and another individual completed 12 months of therapy without any progression of disease.
Shah and colleagues point out that while their study findings are negative with respect to the primary endpoint, "achievement of a durable partial response and a prolonged stable disease for 12 months in two patients is intriguing given the well-tolerated nature of celecoxib."
"Successful accrual and timely completion of our phase II clinical trial in this relatively uncommon patient population of refractory progressive DTC demonstrates feasibility of such trials," they conclude.