title: Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study.
abstract: BACKGROUND
  We describe the long-term outcome after clinical introduction and dose escalation of somatostatin receptor targeted therapy with [90Y-DOTA]-TOC in patients with metastasized neuroendocrine tumors.
  
  
  METHODS
  In a clinical phase I dose escalation study we treated patients with increasing [90Y-DOTA]-TOC activities. Multivariable Cox regression and competing risk regression were used to compare efficacy and toxicities of the different dosage protocols.
  
  
  RESULTS
  Overall, 359 patients were recruited; 60 patients were enrolled for low dose (median: 2.4 GBq/cycle, range 0.9-7.8 GBq/cycle), 77 patients were enrolled for intermediate dose (median: 3.3 GBq/cycle, range: 2.0-7.4 GBq/cycle) and 222 patients were enrolled for high dose (median: 6.7 GBq/cycle, range: 3.7-8.1 GBq/cycle) [90Y-DOTA]-TOC treatment. The incidences of hematotoxicities grade 1-4 were 65.0%, 64.9% and 74.8%; the incidences of grade 4/5 kidney toxicities were 8.4%, 6.5% and 14.0%, and the median survival was 39 (range: 1-158) months, 34 (range: 1-118) months and 29 (range: 1-113) months. The high dose protocol was associated with an increased risk of kidney toxicity (Hazard Ratio: 3.12 (1.13-8.59) vs. intermediate dose, p = 0.03) and a shorter overall survival (Hazard Ratio: 2.50 (1.08-5.79) vs. low dose, p = 0.03).
  
  
  CONCLUSIONS
  Increasing [90Y-DOTA]-TOC activities may be associated with increasing hematological toxicities. The dose related hematotoxicity profile of [90Y-DOTA]-TOC could facilitate tailoring [90Y-DOTA]-TOC in patients with preexisting hematotoxicities. The results of the long-term outcome suggest that fractionated [90Y-DOTA]-TOC treatment might allow to reduce renal toxicity and to improve overall survival. (ClinicalTrials.gov number NCT00978211).
authors: Institute of Nuclear Medicine, University Hospital Basel, CH. nicolas.marincek@gmail.com
authors: Nicolas
authors: N
authors: Marincek
authors: Ann-Catherine
authors: AC
authors: Jörg
authors: Philippe
authors: P
authors: Brunner
authors: Christian
authors: C
authors: Schindler
authors: Michael T
authors: MT
authors: Koller
authors: Christoph
authors: C
authors: Rochlitz
authors: Jan
authors: J
authors: Müller-Brand
authors: Helmut R
authors: HR
authors: Maecke
authors: Matthias
authors: M
authors: Briel
authors: Martin A
authors: MA
authors: Walter
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000532:radiotherapy*; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011878:Radiotherapy / Q000379:methods*; D013004:Somatostatin / Q000627:therapeutic use*; D055815:Young Adult; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D015021:Yttrium Radioisotopes; D013004:Somatostatin; D015282:Octreotide; C106246:Edotreotide