title: [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial.
abstract: BACKGROUND
  The authors aimed to explore the efficacy of (90)Yttrium-1,4,7,10-tetra-azacyclododecane N,N',N'',N'''-tetraacetic acid [(90)Y-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 [(90)Y-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 [(90)Y-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 [(90)Y-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 [(90)Y-DOTA]-TOC in metastasized iodine-refractory thyroid cancer was associated with longer survival. Upcoming trials should aim to increase the number of treatment cycles.
authors.affiliation: Institute of Nuclear Medicine, University Hospital Basel, Switzerland.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Iten
authors.forename: Beat
authors.initials: B
authors.lastname: Muller
authors.forename: Christian
authors.initials: C
authors.lastname: Schindler
authors.forename: Helmut
authors.initials: H
authors.lastname: Rasch
authors.forename: Christoph
authors.initials: C
authors.lastname: Rochlitz
authors.forename: Daniel
authors.initials: D
authors.lastname: Oertli
authors.forename: Helmut R
authors.initials: HR
authors.lastname: Maecke
authors.forename: Jan
authors.initials: J
authors.lastname: Muller-Brand
authors.forename: Martin A
authors.initials: MA
authors.lastname: Walter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019008:Drug Resistance, Neoplasm; D005260:Female; D006571:Heterocyclic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007455:Iodine / Q000627:therapeutic use; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D013954:Thyroglobulin / Q000097:blood*; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000401:mortality
chemical_list: D006571:Heterocyclic Compounds; D007457:Iodine Radioisotopes; D009942:Organometallic Compounds; C113625:yttrium(III)-1,4,7,10-tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid; D013954:Thyroglobulin; D007455:Iodine