Related ACE Reports
- Published: Apr 2014
- ACE Report #6335
Early vs standard zoledronic acid treatments for prostate cancer metastatic to bone
Study Type: Therapy
OE Level of Evidence: 2
Journal Level of Evidence: N/A
|Sponsor:||Fred Saad, Amgen, Novartis; Michael Morris, sanofi-aventis, Bayer HealthCare Pharmaceuticals, EXINI Diagnostics, Algeta|
Why was this study needed now?
For individuals with prostate cancer, development of concomitant bone metastases significantly impacts morbidity and mortality. Numerous skeletal-related events (SREs) can occur as a consequence of metastases to the bone. The bisphosphonate, zoledronic acid, has been previously demonstrated in one study to prolong time to first SRE in a population of men with castration-resistant prostate cancer undergoing androgen-deprivation therapy. Its efficacy and safety, however, has yet to be determined. Due to the long treatment response duration associated with ADT and the well-documented adverse effects of prolonged zoledronic acid use, this study evaluated the benefits of early administration.
What was the principal research question?
How does the early administration of zoledronic acid compare to the standard administration initiated after progression to castration-resistant disease, in patients with castration-sensitive prostate cancer, when assessed approximately 12 months after treatment initiation?
|Population:||645 patients, >18 years of age, with prostate adenocarcinoma (confirmed histologically), at least one bone metastasis (confirmed radiographically), and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 were included. All patients received ADT less than or equal to 6 months prior to group allocation and continued treatment throughout the study period. Treatment in both groups was continued until confirmation of progressive disease (new bone metastases, or prostate-specific antigen [PSA] progression), at which point open-label zoledronic acid was administered (15 minutes in duration, once every 3 weeks) until development of first SRE.|
|Intervention:||Zoledronic acid: Patients received intravenous zoledronic acid for 15 minutes in duration once every 4 weeks. Patients with baseline creatinine clearances >60 mL/min, 50-60 mL/min, 40-49 mL/min, and 30-39 mL/min were given respective starting doses of 4.0 mg, 3.5 mg, 3.3 mg, and 3.0 mg. (n=323; Median age: 66.1 years)|
|Comparison:||Placebo: Patients received intravenous sterile saline for 15 minutes in duration once every 4 weeks. (n=322; Median age: 66.7 years)|
|Outcomes:||The primary outcome measure was time to first SRE (date of randomization to: radiation therapy to the bone, clinical fracture, spinal cord compression, surgery to the bone, or death relating to prostate cancer). Secondary outcomes included overall survival, progression-free survival (PFS; date of randomization to: first bone progression, PSA progression, or death), and safety (adverse events). *Final analysis was to be completed once 470 SREs were observed.|
|Time:||Patients were assessed every 4 weeks and once every 3 weeks for open-label treatment. Median time on study in the zoledronic acid group and placebo group was 11.8 months and 13.6 months respectively.|
What were the important findings?
What should I remember most?
How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.