Phase II study of celecoxib in metastatic differentiated thyroid carcinoma.
BACKGROUND
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.


METHODS
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.


METHODS
Ambulatory patients were from tertiary referral academic medical centers.


METHODS
Patients in the study had progressive metastatic DTC and had failed prior standard therapy.


METHODS
Patients were treated with celecoxib 400 mg orally twice a day for 12 months.


METHODS
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.
Mrozek
Ewa
E
Division of Hematology, Departments of Internal Medicine, The Ohio State University Thyroid Cancer Unit, The Ohio State University Medical Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, Columbus, Ohio 43210, USA.
Kloos
Richard T
RT
Ringel
Matthew D
MD
Kresty
Laura
L
Snider
Paulette
P
Arbogast
Daria
D
Kies
Merrill
M
Munden
Reginald
R
Busaidy
Naifa
N
Klein
Mary Jean
MJ
Sherman
Steven I
SI
Shah
Manisha H
MH
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068579:Celecoxib; D051546:Cyclooxygenase 2 / Q000032:analysis; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011720:Pyrazoles / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000201:enzymology
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D051546:Cyclooxygenase 2; D000068579:Celecoxib