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: a report from the PROMID Study Group.
abstract: OBJECTIVE
  Somatostatin analogs are indicated for symptom control in patients with gastroenteropancreatic neuroendocrine tumors (NETs). The ability of somatostatin analogs to control the growth of well-differentiated metastatic NETs is a matter of debate. We performed a placebo-controlled, double-blind, phase IIIB study in patients with well-differentiated metastatic midgut NETs. The hypothesis was that octreotide LAR prolongs time to tumor progression and survival.
  
  
  METHODS
  Treatment-naive patients were randomly assigned to either placebo or octreotide LAR 30 mg intramuscularly in monthly intervals until tumor progression or death. The primary efficacy end point was time to tumor progression. Secondary end points were survival time and tumor response. This report is based on 67 tumor progressions and 16 observed deaths in 85 patients at the time of the planned interim analysis.
  
  
  RESULTS
  Median time to tumor progression in the octreotide LAR and placebo groups was 14.3 and 6 months, respectively (hazard ratio [HR] = 0.34; 95% CI, 0.20 to 0.59; P = .000072). After 6 months of treatment, stable disease was observed in 66.7% of patients in the octreotide LAR group and 37.2% of patients in the placebo group. Functionally active and inactive tumors responded similarly. The most favorable effect was observed in patients with low hepatic tumor load and resected primary tumor. Seven and nine deaths were observed in the octreotide LAR and placebo groups, respectively. The HR for overall survival was 0.81 (95% CI, 0.30 to 2.18).
  
  
  CONCLUSIONS
  Octreotide LAR significantly lengthens time to tumor progression compared with placebo in patients with functionally active and inactive metastatic midgut NETs. Because of the low number of observed deaths, survival analysis was not confirmatory.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology and Endocrinology, Institute of Medical Biometry and Epidemiology, Philipps University, Marburg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Rinke
authors.forename: Hans-Helge
authors.initials: HH
authors.lastname: Müller
authors.forename: Carmen
authors.initials: C
authors.lastname: Schade-Brittinger
authors.forename: Klaus-Jochen
authors.initials: KJ
authors.lastname: Klose
authors.forename: Peter
authors.initials: P
authors.lastname: Barth
authors.forename: Matthias
authors.initials: M
authors.lastname: Wied
authors.forename: Christina
authors.initials: C
authors.lastname: Mayer
authors.forename: Behnaz
authors.initials: B
authors.lastname: Aminossadati
authors.forename: Ulrich-Frank
authors.initials: UF
authors.lastname: Pape
authors.forename: Michael
authors.initials: M
authors.lastname: Bläker
authors.forename: Jan
authors.initials: J
authors.lastname: Harder
authors.forename: Christian
authors.initials: C
authors.lastname: Arnold
authors.forename: Thomas
authors.initials: T
authors.lastname: Gress
authors.forename: Rudolf
authors.initials: R
authors.lastname: Arnold
mesh_terms: D015746:Abdominal Pain / Q000139:chemically induced; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017567:Karnofsky Performance Status; D019394:Ki-67 Antigen / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008297:Male; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000009:adverse effects / Q000627:therapeutic use*; D010919:Placebos; D011379:Prognosis; D011446:Prospective Studies; D011788:Quality of Life; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019394:Ki-67 Antigen; D010919:Placebos; D015282:Octreotide