title: Randomized controlled clinical trial of a combination of somatostatin analog and dexamethasone plus zoledronate vs. zoledronate in patients with androgen ablation-refractory prostate cancer.
abstract: BACKGROUND
  As previously shown, the combination of standard androgen ablation therapy with somatostatin analog and dexamethasone in metastatic androgen ablation-refractory (stage D3) prostate cancer (PrCa) patients has a favorable profile of side-effects, durable objective antitumor activity (up to 60% partial response rate) and palliative effects. Bisphosphonates interfere with bone remodeling at the sites of PrCa bone metastases and have been postulated to have indirect and/or direct anti-PrCa activity.
  
  
  METHODS
  A randomized controlled clinical trial was conducted to compare a combination of somatostatin analog (octreotide 20 mg i.m. every 28 days) and oral dexamethasone (4 mg daily for 1 month, gradually reduced to 1 mg daily by the fourth month, with a 1 mg daily maintenance dose thereafter) plus zoledronate (4 mg i.v. every 4 weeks) vs. zoledronate only. All patients in both arms remained in basic androgen blockade throughout the study.
  
  
  RESULTS
  Thirty-eight stage D3 patients (mean age 72.8 +/- 6.8 years) were randomized to either treatment arm of the study. The trial was stopped after a pre-specified interim analysis met the criteria for early closure, i.e. significant difference in outcomes between the two treatment arms. Partial responses (PR, > or =50% PSA decline) were observed in 13 out of 20 patients with combination therapy vs. none with zoledronate. The combination therapy arm had significantly better outcome with respect to median progression-free survival (7.0 vs. 1.0 months, p < 0.0001), median overall survival (OS) (12.0 vs. 9.0 months, p = 0.0027), median PrCa-specific OS (defined as time from onset of therapy until PrCa-related death) (16 vs. 9.0 months, p = 0.0005) and median duration of bone pain improvement (>14 vs. 4 months p = 0.00001 by log-rank tests).
  
  
  CONCLUSIONS
  For androgen ablation-refractory metastatic PrCa patients under androgen ablation, the combination of dexamethasone, somatostatin analog and zoledronate offered superior objective and palliative clinical responses than zoledronate alone.
authors.affiliation: Department of Experimental Physiology, Medical School, University of Athens, Goudi-Athens, Attiki 115 27, Greece.
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Mitsiades
authors.forename: John
authors.initials: J
authors.lastname: Bogdanos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karamanolakis
authors.forename: Constantine
authors.initials: C
authors.lastname: Milathianakis
authors.forename: Theodoros
authors.initials: T
authors.lastname: Dimopoulos
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D004164:Diphosphonates / Q000008:administration & dosage; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome; D000077211:Zoledronic Acid
chemical_list: D000726:Androgen Antagonists; D004164:Diphosphonates; D007093:Imidazoles; D013004:Somatostatin; D000077211:Zoledronic Acid; D003907:Dexamethasone