Abstract
Rosiglitazone is a peroxisome proliferator-activated receptor (PPAR) gamma agonist that has shown promise as both an antiproliferative and redifferentiating agent for the treatment of thyroid cancer in preclinical studies. We investigated the efficacy and side effects of rosiglitazone therapy in patients with differentiated thyroid cancer of follicular cell origin that fails to take up radioiodine or is unresectable. Twenty patients with differentiated thyroid cancer were enrolled in an open-label, phase II trial of oral rosiglitazone treatment (4 mg daily for 1 week, then 8 mg daily for 7 weeks). Five of 20 patients had a positive radioiodine scan after rosiglitazone treatment. Four patients had radioiodine uptake in the neck and one patient had uptake in the pelvis. Unstimulated thyroglobulin levels after rosiglitazone treatment increased in five patients, remained stable in 12 patients, and decreased in three patients. Seven patients had progressive disease on follow-up cross-sectional imaging; six patients in the size and number of lung metastasis and two patients in the size of the neck tumors. Overall, five patients had a partial response (decreased thyroglobulin or positive radioiodine uptake), three patients had stable disease (no change in thyroglobulin and radioiodine uptake status), and 12 patients had disease progression (increased thyroglobulin). By RECIST criteria, no patient had a complete or partial response to rosiglitazone treatment at 3 months follow-up. The mean follow-up time after protocol treatment was 12 months (median 12 months). Our findings suggest that rosiglitazone therapy may induce radioiodine uptake and reduce serum thyroglobulin levels in some patients with differentiated thyroid cancer but this did not result in clinically significant response on long-term follow-up. Moreover, no patients had response to rosiglitazone therapy by anatomic imaging studies.
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