Study of Zoledronic Acid for Patients With Hormone-sensitive Bone Metastases From Prostate Cancer

• Overall Survival at 18 Months and 3 Years [ Time Frame: month 18, year 3 ] [ Designated as safety issue: Yes ]
  Overall survival (OS) time was measured from the start of study drug to the date of death due to any cause.
• Time to Occurrence of SRE or Death [ Time Frame: 18 Months ] [ Designated as safety issue: Yes ]
  Time from randomization to the first detected skeletal related event or death. This endpoint is the same as the primary endpoint with the modification that deaths are considered events.
• Skeletal-related Event(SRE)-Free Survival [ Time Frame: 36 months ] [ Designated as safety issue: No ]
  Time from randomization until the first detected SRE. Patients who were still SRE-free at 3 years were censored.
• Multiple Event Analysis of Skeletal Related Events [ Time Frame: Year 3 ] [ Designated as safety issue: No ]
  As some patients are expected to suffer more than one skeletal-related event, multiple event analysis was used to explore any difference in timing and frequency of SREs. Multiple event analysis was only performed if there was a significant difference in the primary endpoint of SRE-free survival.

This study aims to determine whether early treatment with zoledronic acid, that is given during the early phase of advanced prostate cancer, will be more efficacious than delayed treatment

• Drug: Zoledronic Acid

  Zoledronic acid was provided by Novartis in vials containing 4 mg/5 mL liquid concentrate. Prior to administration, the liquid concentrate from one vial was to be further diluted with 100 mL of calcium-free infusion solution (0.9 % weight by volume sodium chloride solution or 5 % weight by volume glucose solution). If refrigerated, the solution had to be allowed to reach room temperature before administration.

  After addition of the liquid concentrate to the infusion media, the infusion solution was to be used as soon as practicable to reduce the risk of microbiological hazard. If storage of the solution was necessary, it had to be refrigerated at temperatures between 2-8 degrees C and was to be used within 24 hours.

  The infusion solution containing 4 mg zoledronic acid was to be administered every 4 weeks as an i.v. infusion over no less than 15 minutes.

• Drug: Androgen Deprivation Therapy (ADT)
  Androgen deprivation therapy (ADT) was to be administered according to institutional protocols, in accordance with relevant prescribing information. The type and duration of androgen deprivation was at the discretion of the treating specialist, and could include orchiectomy where this would normally have been performed. Androgen deprivation therapy was provided by the investigational center, or obtained by the patient from usual sources. Anti-androgen monotherapy and intermittent ADT were excluded in the first 12 months of the study.

• Experimental: Early Group
  Zoledronic acid 4 mg i.v. infusion every 4 weeks, commencing at Baseline.
  Intervention: Drug: Zoledronic Acid
• Experimental: Delayed group
  Zoledronic acid 4 mg i.v. infusion every 4 weeks, commencing no sooner than 12 months after their baseline visit, and not until they have had three rises in PSA level from Baseline, one of which must be a least 10 ng/mL greater than the baseline Serum Prostate-specific Antigen (PSA) level.
  Intervention: Drug: Androgen Deprivation Therapy (ADT)

Inclusion Criteria:

• prostate cancer
• at least one bone metastasis
• receiving or about to receive androgen deprivation therapy (ADT)

Exclusion Criteria:

• previous ADT failure
• previous or current treatment with another bone-protecting agent, chemotherapy or targeted therapy
• abnormal renal function

Other protocol-defined inclusion/exclusion criteria may apply.