title: Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0,Tyr3]octreotate: toxicity, efficacy, and survival.
abstract: OBJECTIVE
  Despite the fact that most gastroenteropancreatic neuroendocrine tumors (GEPNETs) are slow-growing, median overall survival (OS) in patients with liver metastases is 2 to 4 years. In metastatic disease, cytoreductive therapeutic options are limited. A relatively new therapy is peptide receptor radionuclide therapy with the radiolabeled somatostatin analog [(177)Lu-DOTA(0),Tyr(3)]octreotate. Here we report on the toxicity and efficacy of this treatment, performed in over 500 patients.
  
  
  METHODS
  Patients were treated up to a cumulative dose of 750 to 800 mCi (27.8-29.6 GBq), usually in four treatment cycles, with treatment intervals of 6 to 10 weeks. Toxicity analysis was done in 504 patients, and efficacy analysis in 310 patients.
  
  
  RESULTS
  Any hematologic toxicity grade 3 or 4 occurred after 3.6% of administrations. Serious adverse events that were likely attributable to the treatment were myelodysplastic syndrome in three patients, and temporary, nonfatal, liver toxicity in two patients. Complete and partial tumor remissions occurred in 2% and 28% of 310 GEPNET patients, respectively. Minor tumor response (decrease in size > 25% and < 50%) occurred in 16%. Median time to progression was 40 months. Median OS from start of treatment was 46 months, median OS from diagnosis was 128 months. Compared with historical controls, there was a survival benefit of 40 to 72 months from diagnosis.
  
  
  CONCLUSIONS
  Treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate has few adverse effects. Tumor response rates and progression-free survival compare favorably to the limited number of alternative treatment modalities. Compared with historical controls, there is a benefit in OS from time of diagnosis of several years.
authors.affiliation: Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. d.j.kwekkeboom@erasmusmc.nl
authors.forename: Dik J
authors.initials: DJ
authors.lastname: Kwekkeboom
authors.forename: Wouter W
authors.initials: WW
authors.lastname: de Herder
authors.forename: Boen L
authors.initials: BL
authors.lastname: Kam
authors.forename: Casper H
authors.initials: CH
authors.lastname: van Eijck
authors.forename: Martijn
authors.initials: M
authors.lastname: van Essen
authors.forename: Peter P
authors.initials: PP
authors.lastname: Kooij
authors.forename: Richard A
authors.initials: RA
authors.lastname: Feelders
authors.forename: Maarten O
authors.initials: MO
authors.lastname: van Aken
authors.forename: Eric P
authors.initials: EP
authors.lastname: Krenning
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002276:Carcinoid Tumor / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology; D056486:Chemical and Drug Induced Liver Injury; D018572:Disease-Free Survival; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000139:chemically induced; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology; D015282:Octreotide / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000009:adverse effects / Q000627:therapeutic use*; D018570:Risk Assessment; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009942:Organometallic Compounds; D019275:Radiopharmaceuticals; C447941:lutetium Lu 177 dotatate; D015282:Octreotide