Radioiodine therapy after pretreatment with bexarotene for metastases of differentiated thyroid carcinoma

Abstract

To evaluate the effects of pretreatment with the retinoid X receptor (RXR) agonist bexarotene on the efficacy of radioiodine therapy for metastases of differentiated thyroid carcinoma (DTC) with limited uptake of radioiodine (I-131). An open prospective intervention study. Eight patients with metastases of DTC, with insufficient uptake of I-131 who showed increased uptake of radioiodine after previous treatment with bexarotene were treated with radioiodine (7400 MBq), preceded by 6 weeks of treatment with bexarotene 300 mg/day. Outcome parameters were serum thyroglobulin (Tg) levels and dimensions of metastases at computed tomography (CT), measured before and 6 months after therapy. Tissues of primary tumours were stained with antibodies against retinoic acid receptor (RAR) and RXR subtypes. Bexarotene pretreatment induced radioiodine uptake in metastases in all eight patients, although uptake was only discernable at single photon emission computed tomography (SPECT) and had incomplete matching with the metastases visualized by CT scanning. Six months after radioiodine therapy, six patients had progressive disease (defined as a > 10% increase in serum Tg and/or a > 25% increase in tumour dimensions), whereas two patients had stable disease. No relationship was observed between retinoid receptor staining pattern at immunohistochemistry and the outcome of therapy. Bexarotene therapy did not result in restoration of susceptibility to radioiodine therapy.