RT Journal Article SR Electronic T1 Randomized Controlled Clinical Trial of a Combination of Somatostatin Analog and Dexamethasone Plus Zoledronate vs. Zoledronate in Patients with Androgen Ablation-refractory Prostate Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 3693 OP 3700 VO 26 IS 5B A1 MITSIADES, CONSTANTINE S. A1 BOGDANOS, JOHN A1 KARAMANOLAKIS, DIMITRIOS A1 MILATHIANAKIS, CONSTANTINE A1 DIMOPOULOS, THEODOROS A1 KOUTSILIERIS, MICHAEL YR 2006 UL http://ar.iiarjournals.org/content/26/5B/3693.abstract 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<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). 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.