PT - JOURNAL ARTICLE AU - MITSIADES, CONSTANTINE S. AU - BOGDANOS, JOHN AU - KARAMANOLAKIS, DIMITRIOS AU - MILATHIANAKIS, CONSTANTINE AU - DIMOPOULOS, THEODOROS AU - KOUTSILIERIS, MICHAEL TI - Randomized Controlled Clinical Trial of a Combination of Somatostatin Analog and Dexamethasone Plus Zoledronate <em>vs.</em> Zoledronate in Patients with Androgen Ablation-refractory Prostate Cancer DP - 2006 Sep 01 TA - Anticancer Research PG - 3693--3700 VI - 26 IP - 5B 4099 - http://ar.iiarjournals.org/content/26/5B/3693.short 4100 - http://ar.iiarjournals.org/content/26/5B/3693.full SO - Anticancer Res2006 Sep 01; 26 AB - 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. Materials and 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, ≥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&lt;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 (&gt;14 vs. 4 months p=0.00001 by log-rank tests). Conclusion: 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.