title: Placebo-Controlled, Double-Blind, Prospective, Randomized Study on the Effect of Octreotide LAR in the Control of Tumor Growth in Patients with Metastatic Neuroendocrine Midgut Tumors (PROMID): Results of Long-Term Survival.
abstract: BACKGROUND
  Somatostatin analogs have been shown to control the growth of well-differentiated metastatic neuroendocrine tumors. Their effect on overall survival is a matter of debate. We analyzed the prognostic significance of early treatment with octreotide LAR and of hepatic tumor load in the PROMID trial cohort.
  
  
  METHODS
  Between 2001 and 2008, 85 treatment-naïve patients were randomly assigned to monthly octreotide LAR 30 mg or placebo until tumor progression or death. Post-study treatment was at the discretion of the investigator. Upon disease progression, 38 out of 43 placebo patients (88.4%) received octreotide LAR. For survival, patients were followed until May 2014.
  
  
  RESULTS
  Forty-eight out of 85 patients (56.5%) died. In 38 patients (79.2%), death was tumor related. The median overall survival (84.7 and 83.7 months) was only slightly different in patients assigned to octreotide and placebo [HR = 0.83 (95% CI: 0.47-1.46); p = 0.51]. The median overall survival was 84.7 months for all 85 patients, 107.6 months in the low-tumor-load (n = 64) and 57.5 months in the high-tumor-load (n = 21) subgroups [HR = 2.49 (95% CI: 1.36-4.55); p = 0.002]. There was a trend towards improved overall survival in patients with a low hepatic tumor load receiving octreotide compared to placebo ['median not reached' and 87.2 months; HR = 0.59 (95% CI: 0.29-1.2); p = 0.142].
  
  
  CONCLUSIONS
  The extent of tumor burden is a predictor for shorter survival. Overall survival was similar in patients receiving octreotide LAR or placebo treatment at randomization. Crossover of the majority of placebo patients to octreotide LAR may have confounded the data on overall survival.
authors.affiliation: Division of Gastroenterology and Endocrinology, University Hospital Marburg (UKGM), Marburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rinke
authors.forename: Michael
authors.initials: M
authors.lastname: Wittenberg
authors.forename: Carmen
authors.initials: C
authors.lastname: Schade-Brittinger
authors.forename: Behnaz
authors.initials: B
authors.lastname: Aminossadati
authors.forename: Erdmuthe
authors.initials: E
authors.lastname: Ronicke
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Gress
authors.forename: Hans-Helge
authors.initials: HH
authors.lastname: Müller
authors.forename: Rudolf
authors.initials: R
authors.lastname: Arnold
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary; D015282:Octreotide / Q000627:therapeutic use*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D015282:Octreotide