Clinical study of retinoids in redifferentiation therapy of advanced thyroid cancer

Objective: During the course of tumor progression the differentiated morphologic and functional characteristics of differentiated thyroid carcinomas (DTC) disappear. This corresponds to more aggressive growth, metastatic spread, and loss of iodine uptake. Experimental data give strong evidence that differentiated functions of iodine metabolism can be reinduced by retinoic acids. The aim was to assess the changes under all-trans-retinoid treatment. Method: Fifteen of twenty patients with DTC (five follicular, eight papillary, two oxyphilic) were selected for treatment with all-trans-retinoid acid 1-1.5 mg/kg body weight/day over 4 weeks. All patients had advanced tumor stages with prior operative and radioiodine treatment. Extensive tumor invasion, distant metastatic spread, or insufficient or no radioiodine uptake precluded any conventional therapeutic option. Results: Iodine uptake increased in seven patients (two follicular, five papillary). Thyroglobulin (TG) as parameter for tumor mass and differentiation increased in 8 (66%) patients, decreased in 4 (33%), and did not change in 1 (1%). Conclusions: Retinoids do have an effect on differentiation status of DTC and the low rate of side-effects with good tolerability of retinoids, reinducing iodine uptake in 33% of patients. TG levels do not always parallel a response in iodine uptake. (authors)