Significance of baseline bone markers on disease progression and survival in hormone-sensitive prostate cancer with bone metastasis.

PURPOSE: This study evaluated the baseline patient characteristics associated with the time to biochemical progression and overall survival in patients who participated in a phase II trial on zoledronic acid combined with the initial androgen-deprivation therapy for treatment-naïve bone-metastatic prostate cancer. METHODS: Patients received zoledronic acid 4 mg intravenously every 4 weeks for up to 24 months, concomitantly started with bicalutamide 80 mg orally every day and goserelin acetate 10.8 mg subcutaneously every 12 weeks. RESULTS: A total of 53 Japanese patients were enrolled between July 2008 and April 2010, and 52 patients were evaluable. Median follow-up period was 41.6 months. Updated median time to biochemical progression was 25.9 months (95 % confidence interval 14.5-49.9). Higher serum bone-specific alkaline phosphatase was an independent risk factor for time to biochemical progression based on multivariate analysis (hazard ratio 6.51; 95 % confidence interval 2.71-15.62; P < 0.001). Median time to biochemical progression for patients with serum bone-specific alkaline phosphatase level higher than 26 µg/L was 12.7 months. Multivariate analysis indicated that higher serum C-terminal telopeptide of type I collagen independently increased the risk of death (hazard ratio 9.62; 95 % confidence interval 2.11-43.89; P = 0.003). Median overall survival for patients with serum C-terminal telopeptide of type I collagen level higher than 8.0 ng/ml was 31.1 months. CONCLUSIONS: Baseline bone markers can be useful as predictors for disease progression and survival time in patients with bone metastasis from treatment-naïve prostate cancer treated with upfront zoledronic acid concomitantly started with androgen-deprivation therapy.

Phase II trial of zoledronic acid combined with androgen-deprivation therapy for treatment-naïve prostate cancer with bone metastasis.

BACKGROUND: The efficacy of zoledronic acid in patients with treatment-naïve prostate cancer is unclear. We conducted a phase II study to investigate the benefits of combined zoledronic acid and androgen deprivation therapy in treatment-naïve prostate cancer with bone metastasis. The primary endpoint was skeletal-related event-free survival at 24 months. METHODS: Subjects were treatment-naïve patients with histologically confirmed adenocarcinoma of the prostate and radiological evidence of bone metastasis. Treatment consisted of bicalutamide 80 mg daily, goserelin acetate 10.8 mg every 12 weeks, and zoledronic acid 4 mg every 4 weeks. Zoledronic acid was continued for 24 months. RESULTS: Of the patients enrolled between July 2008 and April 2010, 52 were included in the analyses. The median age of the patients was 72 years. The median baseline prostate-specific antigen level was 249.4 ng/mL. The median follow-up period was 33.3 months. The 24-month skeletal-related event-free survival rate was 84.4 % (95 % confidence interval 71.2-91.9). The median time to prostate-specific antigen progression was 25.9 months (95 % confidence interval 14.7-36.3). The median overall survival time was not reached. Improvement in pain or maintenance of no pain during the first 12 weeks was observed in 70 % of patients and the extent of bone disease was decreased in 10 % of patients at 12 months. Grade 3 osteonecrosis of the jaw was observed in three patients (5.8 %). CONCLUSION: Zoledronic acid concomitant with androgen deprivation therapy as initial treatment in patients with treatment-naïve prostate cancer with bone metastasis resulted in an encouraging skeletal-related event-free survival rate at 24 months.

Discovery of a Novel Sn(II)-Based Oxide ß-SnMoO4 for Daylight-Driven Photocatalysis.

Daylight-driven photocatalysts have attracted much attention in the context of "green" technology. Although various active materials have been reported and their applications are rapidly increasing, many are discovered after enormous experimental efforts. Herein the discovery of a novel oxide photocatalyst, ß-SnMoO4, is demonstrated via a rational search of 3483 known and hypothetical compounds with various compositions and structures over the whole range of SnO-MO q/2 (M: Ti, Zr, and Hf (q = 4); V, Nb, and Ta (q = 5); Cr, Mo, and W (q = 6)) pseudobinary systems. Screening using thermodynamic stability, band gap, and band-edge positions by density functional theory calculations identifies ß-SnMoO4 as a potential target. Then a low temperature route is used to successfully synthesize the novel crystal, which is confirmed by X-ray powder diffraction and Mössbauer spectroscopy. ß-SnMoO4 is active for the photocatalytic decomposition of a methylene blue solution under daylight and its activity is comparable to a known photocatalyst, ß-SnWO4.

Zoledronic acid combined with androgen-deprivation therapy may prolong time to castration-resistant prostate cancer in hormone-naïve metastatic prostate cancer patients - A propensity scoring approach.

OBJECTIVE: To clarify the oncological benefit of zoledronic acid for hormone-naïve metastatic prostate cancer, patient outcome of androgen deprivation therapy with zoledronic acid (ADT + Z) and androgen deprivation therapy alone (ADT) was compared. METHODS: Fifty-two patients with pathologically confirmed metastatic prostate cancer were prospectively enrolled and treated with combined androgen blockade (goserelin and bicalutamide) with zoledronic acid (4 mg every 4 weeks for 24 months). A propensity score-match with logistic regression analysis was applied to select 50 pair-matched cohorts (both from ADT + Z and from historical control cohorts who had undergone ADT alone), and patient outcomes were compared. RESULTS: Patients with ADT + Z had significantly longer time to progression (TTP) than those with ADT (median TTP; 24.2 vs. 14.0 months, p = 0.0092), while no significant difference of overall survival between two groups (p = 0.1502). Multivariate analysis for biochemical recurrence revealed treatment with ADT was the sole independent prognostic factor (HR: 1.724, 95% CI: 1.06-2.86, p = 0.0297). CONCLUSION: Combination of zoledronic acid with ADT may prolong time to castration resistant prostate cancer.