title: Combination of somatostatin analog, dexamethasone, and standard androgen ablation therapy in stage D3 prostate cancer patients with bone metastases.
abstract: OBJECTIVE
  Androgen ablation-refractory prostate cancer patients (stage D3) develop painful bone metastases and limited responsiveness to conventional therapies, hence the lack of universally accepted "gold standard" treatment for this poor prognosis clinical setting. We tested the safety and efficacy in stage D3 patients of the combination hormonal therapy, which combines administration of somatostatin analog and dexamethasone with standard androgen ablation monotherapy (luteinizing-hormone releasing-hormone analog or orchiectomy).
  
  
  METHODS
  Thirty eight patients with stage D3 prostate cancer (mean age 71.8 +/- 5.9 years) continued receiving androgen ablation therapy in combination with oral dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg daily by the 4th month, with 1 mg daily maintenance dose thereafter) and somatostatin analog (20 mg octreotide i.m. injections every 28 days).
  
  
  RESULTS
  Twenty-three of 38 patients (60.5%) receiving this combination regimen had partial responses [PR, >/=50% prostate-specific antigen (PSA) decline], 9 (21.1%) had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of patients, their serum PSA levels decreased with treatment but did not return to their respective baselines until the end of follow-up (or death from non-prostate cancer-related causes). The median time-to-return to baseline PSA was 12 months (95% CI, 7-17 months), median progression-free survival was 7 months (95% CI, 4.5-9.5 months), median overall survival was 14 months (95% CI, 10.7-17.4 months), and median prostate cancer-specific overall survival (defined as time from onset of combination therapy until prostate cancer-related death) was 16.0 months (95% CI, 11.9-20.1 months). All patients reported significant and durable improvement of bone pain and performance status (for a median duration of 14 months; 95% CI, 9-19 months), without major treatment-related side effects. We observed a statistically significant (P < 0.01) reduction in serum insulin-like growth factor-1 levels at response to the combination therapy. T levels remained suppressed within castration levels at baseline and throughout therapy, including relapse.
  
  
  CONCLUSIONS
  The combination therapy of dexamethasone plus somatostatin analog and standard androgen ablation manipulation produces objective clinical responses and symptomatic improvement in androgen ablation-refractory refractory prostate cancer patients.
authors.affiliation: Department of Experimental Physiology, Medical School, University of Athens, Goudi-Athens, Greece. mitsiades@dfci.harvard.edu
authors.forename: Michael
authors.initials: M
authors.lastname: Koutsilieris
authors.forename: Constantine S
authors.initials: CS
authors.lastname: Mitsiades
authors.forename: John
authors.initials: J
authors.lastname: Bogdanos
authors.forename: Theodoros
authors.initials: T
authors.lastname: Dimopoulos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karamanolakis
authors.forename: Constantine
authors.initials: C
authors.lastname: Milathianakis
authors.forename: Athanassios
authors.initials: A
authors.lastname: Tsintavis
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D003907:Dexamethasone / Q000008:administration & dosage* / Q000627:therapeutic use; D018450:Disease Progression; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D007987:Gonadotropin-Releasing Hormone / Q000627:therapeutic use; D006728:Hormones / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D011877:Radionuclide Imaging; D013004:Somatostatin / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D006728:Hormones; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin; D003907:Dexamethasone; D017430:Prostate-Specific Antigen