Effects of Rosiglitazone on Radioiodine Negative and Progressive Differentiated Thyroid Carcinoma as Assessed by 124I PET/CT Imaging

Aim: The aim of this study was to evaluate the redifferentiative and antiproliferative effects of rosiglitazone in patients with progressive differentiated thyroid cancer (DTC) without or with negligible overall radioiodine uptake. Materials and Methods: A total of 9 patients with progressive DTC with either no or only negligible radioiodine accumulation were enrolled in this study. Oral rosiglitazone treatment was applied for 6 months (4 mg per day for 2 weeks followed by 8 mg per day). The compatibility of the medication was initially checked twice weekly and then weekly by laboratory tests and clinical evaluation of side effects. The assessments of alterations in the doses absorbed by the tumor and in lesion sizes over the course of rosiglitazone treatment were performed using serial I-124 positron emission tomography and computed tomography imaging. The assessment time points were before enrollment and 3 and 6 months posttreatment initiation. Results: Lesion dosimetry indicated that 5 of 9 patients had an improved lesion absorbed dose per administered activity (LDpA), yielding in radioiodine therapy treatment in 4 patients. One third of the patients (3/9) were unchanged with regard to LDpA, and 1 of 9 had deteriorated LDpA. Volumetric analyses revealed that lesion sizes were regredient in 3 of 9 patients, stable in 4 of 9, and was progressive in 1 of 9. The medication was well-tolerated, and no patient developed clinically important toxicity associated with rosiglitazone treatment. In 2 of 9 of the patients, the medication was terminated after 3 months as a precaution due to progressive heart disease in one patient and bone fracture within a known osteolytic bone lesion in another patient. It is not clear that these complications were caused by rosiglitazone. Conclusion: Rosiglitazone appears to be suitable as off-label therapy in radioiodine-negative and progressive DTC that lacks therapy alternatives. In Europe, rosiglitazone was removed for label use because of reported side effects during diabetes treatment. Further investigations of other available glitazone compounds are necessary.