Retinoic acid in patients with radioiodine non-responsive differentiated thyroid carcinoma

Full text: For the treatment of differentiated thyroid cancer, surgery, radioiodide therapy, and thyrotropin-suppressive thyroxine application represent established therapeutic measures of proven efficiency, affording a good prognosis for this disease. However, in up to 30% of the cases, de-differentiation is observed, giving rise to tumours that are refractory to conventional treatment. Experimental data shows strong evidence that differentiated functions of iodine metabolism can be re-induced by retinoic acids (RA). The aim of our study was to assess the effects of retinoic acid therapy in patients with extensive thyroid tumor involvement, which lost radioiodine uptake ability. Twenty-five patients who received retinoic acid therapy between Feb. 1999 to Dec. 2004 were reviewed retrospectively. There were 15 males and 10 females with a mean age of 52.5 years (16-71 years). Most of them underwent total or near total thyroidectomy before I-131 treatment. Twenty-one patients were papillary carcinoma and four were follicular carcinoma. Twenty-two patients had lung metastasis and three had bone metastasis. Thyroid hormone medications were withdrawn for two weeks in case of triiodothyronine (T3) and five weeks in case of thyroxine (T4). For treatment of bone metastases, an amount of 7.4 GBq (200mCi) of I-131 was given every six months. For treatment of pulmonary metastases an amount of 5.55-7.4 GBq (150-200mCi) was given every six months. In 25 patients with advanced thyroid cancer, whose cancer foci did not concentrate radioiodine, retinoic acid was given for 6 weeks before radioiodine treatment, followed by I-131 treatment. All patients had I-131 scans and thyroglobulin measurements 7 days after administration of I-131. X-ray, bone scan, and ultrasound of the neck were done one month after administration of I-131. One patient received RA therapy four times and two patients received RA twice. In the post-therapy radioiodine scans, radioiodine uptake was noted in 9 patients with lung metastases and in 2 patients with bone metastases. On the whole, in 44% (11/25) of patients re-induction of radioiodine uptake was observed. Levels of thyroglobulin concentration before and after RA therapy did not differ significantly (P>0.05). In our study, all patients completed the treatment and the most frequent side effects were fatigue. Dry skin, mouth and lips occurred in 35% of patients. Most side effects were well tolerated by the patients and reversible following cessation of RA therapy. We conclude that retinoic acid can induce radioiodine uptake and the side effects are well tolerated. However, prospective studies in larger groups of patients are necessary to prove its clinical utility in routine practice. (author)