Bisphosphonates

In MRC-PR05, 311 men with bone metastases who were starting or responding to standard hormonal therapy were randomly assigned to oral sodium clodronate (2,080 mg qd) or a matching placebo for up to 3 years.[47][Level of evidence A1]

In MRC-PR05, 311 men with bone metastases who were starting or responding to standard hormonal therapy were randomly assigned to oral sodium clodronate (2,080 mg qd) or a matching placebo for up to 3 years.[47][Level of evidence A1]

At a median follow-up of 11.5 years, OS was better in the clodronate arm: HRdeath, 0.77 (95% CI, 0.60–0.98; P = .032).

In MRC-PR05, 311 men with bone metastases who were starting or responding to standard hormonal therapy were randomly assigned to oral sodium clodronate (2,080 mg qd) or a matching placebo for up to 3 years.[47][Level of evidence A1]

Five- and 10-year survival rates were 30% and 17% in the clodronate arm versus 21% and 9% in the placebo arm.

A parallel study (MRC-PR04) in men with locally advanced but nonmetastatic disease showed no benefit associated with clodronate.

CALGB-90202 [NCT00079001] was a randomized controlled trial that compared zoledronic acid (4 mg IV every 4 weeks) with placebo in 645 men with androgen deprivation-sensitive prostate cancer that was metastatic to bone. Patients who progressed on hormone-therapy resistance received open-label, zoledronic acid.[48][Level of evidence B1]

CALGB-90202 [NCT00079001] was a randomized controlled trial that compared zoledronic acid (4 mg IV every 4 weeks) with placebo in 645 men with androgen deprivation-sensitive prostate cancer that was metastatic to bone. Patients who progressed on hormone-therapy resistance received open-label, zoledronic acid.[48][Level of evidence B1]

There was no difference between the two study arms in risk of the primary end point of time to skeletal-related events (defined as the need for palliative bone radiation, clinical fracture, spinal cord compression, bone surgery, or death from prostate cancer) after up to 7 years of follow-up.

CALGB-90202 [NCT00079001] was a randomized controlled trial that compared zoledronic acid (4 mg IV every 4 weeks) with placebo in 645 men with androgen deprivation-sensitive prostate cancer that was metastatic to bone. Patients who progressed on hormone-therapy resistance received open-label, zoledronic acid.[48][Level of evidence B1]

There were also no differences in PFS or OS.

In another negative randomized trial (STAMPEDE [NCT00268476]), 1,245 men with locally advanced (M0) or metastatic (M1) prostate cancer, who were initiating long-term hormonal therapy, were randomly assigned in a 2:1:1 ratio to one of three arms: standard of care, celecoxib (400 mg bid for 1 year), and celecoxib plus zoledronic acid (4 mg IV for six 3-week cycles, then 4-week cycles for 2 years).[49]

In another negative randomized trial (STAMPEDE [NCT00268476]), 1,245 men with locally advanced (M0) or metastatic (M1) prostate cancer, who were initiating long-term hormonal therapy, were randomly assigned in a 2:1:1 ratio to one of three arms: standard of care, celecoxib (400 mg bid for 1 year), and celecoxib plus zoledronic acid (4 mg IV for six 3-week cycles, then 4-week cycles for 2 years).[49]

After a median follow-up of 69 months, there was no detectable improvement in survival associated with either celecoxib or celecoxib plus zoledronic acid.

In another negative randomized trial (STAMPEDE [NCT00268476]), 1,245 men with locally advanced (M0) or metastatic (M1) prostate cancer, who were initiating long-term hormonal therapy, were randomly assigned in a 2:1:1 ratio to one of three arms: standard of care, celecoxib (400 mg bid for 1 year), and celecoxib plus zoledronic acid (4 mg IV for six 3-week cycles, then 4-week cycles for 2 years).[49]

Although survival was better in patients with M disease who received celecoxib plus zoledronic acid than in patients with M1 disease who received the standard of care (HRdeath, 0.78; 95% CI, 0.62–0.98), a formal test for interaction with metastasis status was not statistically significant; therefore, the unexpected finding can only be considered hypothesis-generating.