Peptide Receptor Radionuclide Therapy of Differentiated Thyroid Cancer: Efficacy and Toxicity

Abstract

In rare cases of differentiated thyroid carcinoma (DTC), radioiodine treatment is no longer effective due to cell dedifferentiation. Targeting somatostatin receptors in DTC cells by radiolabelled somatostatin analogues could provide an alternative therapy option. The aim of this study was to evaluate safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced, non-iodine avid DTC. Eleven patients aged 47–81 years (median: 65 years) with a history of several courses of radioiodine therapy, increasing thyroglobulin (Tg) and negative whole body scan, were qualified to the study. After confirming receptor expression by somatostatin receptor scintigraphy, PRRT with yttrium-90 labelled analogue was initiated. Fractionated treatment protocol was used with four doses of 90Y-DOTA-TOC in 12-week intervals. Activity of each dose was 3.7 GBq (100 mCi). Of 11 patients, 5 died before receiving the fourth course of PRRT. In the remaining six patients, morphological response, evaluated 3 months after the last course using RECIST criteria showed partial remission (PR) in one patient, stable disease (SD) in two patients and progressive disease (PD) in three patients. Biochemical response based on Tg measurements before and after PRRT showed PR in one patient, SD in four patients and PD in one patient. Median survival was 21 months from the first course of PRRT. Only minor and transient hematological toxicity was observed in some patients. We conclude that PRRT is generally well-tolerated and may be a valuable option for some patients with radioiodine-refractory DTC.

The Treatment of Advanced Thyroid Cancer in the Age of Novel Targeted Therapies

“…In another phase 2 study of 52 patients including 45 with RAIR DTC and 6 with MTC, an ORR of 35% (95% CI 22–49) was reported with axitinib, with a median duration of response of 17 m (95% CI 14–26) [35]. A phase 2 study of 37 patients with RAIR DTC treated with pazopanib demonstrated an ORR of 49% (95% CI 35–68), which were all PRs with a median PFS of 11.7 m (1 to > 23 m) [32], and an additional phase 2 trial is pending (NCT01813136) [138]. Pazopanib has also been studied in 35 patients with MTC, demonstrating a PR rate of 14% (90% CI 5.8–28), with a median PFS of 9.4 m [36].…”

“…Finally, a number of other exciting agents with various mechanisms of action are undergoing earlier-phase translational study, including other MAPK-pathway inhibitors, additional TKIs, histone deacetylase inhibitors, PPAR-γ-directed agents, proteosome inhibitors, immunotherapy strategies, farnesyl transferase inhibitors, somatostatin receptor radionuclide therapy, and gene therapy techniques. To date, no randomized controlled clinical evidence exists to support their use in thyroid cancer, but a role for these agents may develop as additional data becomes available [10,11,80,82,85,108–118,119–138]. …”

99mTc-EDDA/HYNIC-TOC in the diagnosis of differentiated thyroid carcinoma refractory to radioiodine treatment

“…Demonstration of somatostatin receptor expression by the means of SRS is a crucial criterion to qualify to such an experimental treatment. The results of PRRT in DTC in our center have been published elsewhere [49]. PRRT was generally well-tolerated but the outcome was rather poor in majority of cases of radioiodine-refractory DTC.…”

Appropriate Use Criteria for Nuclear Medicine in the Evaluation and Treatment of Differentiated Thyroid Cancer

“…Scenario 1: 177 Lu-DOTATATE Treatment for Documented SSTR-Expressing RAI-Refractory Thyroid Cancer (Score 4 -May Be Appropriate). PRRT with radiolabeled somatostatin analogs has shown promise for the treatment of RAI-refractory metastatic DTC with a demonstrated objective response rate of 27%-60% tumor reduction, as determined by radiologic measurements following RECIST (143,144).…”