[90Yttrium-DOTA]-TOC Response Is Associated With Survival Benefit in Iodine-Refractory Thyroid Cancer Long-term Results of a Phase 2 Clinical Trial

BACKGROUND: The authors aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N '',N'''-tetraacetic acid [Y-90-DOTA]-Tyr(3)-octreotide (TOC) in advanced iodine-refractory thyroid cancer. METHODS: In a phase 2 trial, the authors investigated biochemical response (assessed by serum thyroglobulin levels), survival, and the long-term safety profile of systemic [Y-90-DOTA]-TOC treatment in metastasized iodine-refractory thyroid cancer. Adverse events were assessed according to the National Cancer Institute criteria. Survival analyses were performed by using multiple regression models. RESULTS: A total of 24 patients were enrolled. A median cumulative activity of 13.0 GBq (range, 1.7-30.3 GBq) was administered. Response was found in 7 (29.2%) patients. Eight (33.3%) patients developed hematologic toxicity grade 1-3, and 4 (16.7%) patients developed renal toxicity grade 1-4. The median survival was 33.4 months (range, 3.6-126.8 months) from time of diagnosis and 16.8 months (range, 1.8-99.1 months) from time of first [Y-90-DOTA]-TOC treatment. Response to treatment was associated with longer survival from time of diagnosis (hazard ratio [HR], 0.17; 95% confidence interval [CI], 0.03-0.92; P = .04) and from time of first [Y-90-DOTA]-TOC therapy (HR, 0.20; 95% CI, 0.04-0.94; P = .04). The visual grade of scintigraphic tumor uptake was not associated with treatment response (odds ratio [OR], 0.98; 95% CI, 0.26-3.14; P = 1.00). CONCLUSIONS: Response to [90Y-DOTA]-TOC in metastasized iodine-refractory thyroid cancer was associated with longer survival. Upcoming trials should aim to increase the number of treatment cycles. Cancer 2009;115:2052-62. (C) 2009 American Cancer Society.