Abstract
Objective: Patients with metastases of differentiated thyroid carcinoma that fail to trap iodine or are unresectable have a poor prognosis. Recent studies with PPAR-γ agonists have shown promising effects on the re-differentiation and even tumor regression of thyroid cancers in animal models and in humans. The aim of the present study was to assess the effects of prolonged rosiglitazone treatment in those patients with metastases that lost radioiodine uptake.
Methods: Between May 2005 and March 2008, 13 patients (5 follicular, 8 papillary) were enrolled in the study. All patients had advanced stage tumors with prior surgery and radioiodine therapy (RIT), distant metastases and insufficient or missing uptake of radioiodine. They were treated with rosiglitazone (4 mg/d for four weeks, followed by 8 mg/d for 5 months) in addition to TSH-supressive therapy before RIT. Changes in iodine-uptake, response of target lesions, and serum thyroglobulin (Tg) levels before and after RIT were measured.
Results: After 6 months treatment with rosiglitazone iodine uptake significantly increased in 7/13 patients. Although in 3 of the remaining 6 patients iodine-scan remained negative, thyroglobulin levels increased more than two-fold after RIT 3 days after RIT and decreased below the initial level thereafter. In 1/6 iodine-positive lymph node was detected after RIT. F18-FDG PET, performed in 8/13 patients, revealed metastases of significant metabolism in 6 patients, including 3 patients with an increased radioiodine uptake and 3 patients without. Serious side effects have not been observed.
Conclusions: We could confirm earlier experiences, demonstrating that treatment with rosiglitazone restored iodine uptake, allowing effective RIT in more than half of the patients with differentiated thyroid cancer. In contrast to previous studies we extended the time of rediffentiation therapy, which might explain the higher response rate (8/13). No side effects occurred under rosiglitazone, except slight oedema in one patient.