Mason MD et al. (2007) Oral sodium clodronate for nonmetastatic prostate cancer—results of a randomized double-blind placebo-controlled trial: Medical Research Council PR04 (ISRCTN61384873). J Natl Cancer Inst 99: 765–776

Adjuvant sodium clodronate, a first-generation bisphosphonate, showed no benefit in patients with nonmetastatic prostate cancer in a recent randomized, double-blind, placebo-controlled trial.

Mason and colleagues from the UK tested whether bisphosphonates slow the development of symptomatic bone metastases in prostate cancer patients. The study included men recently diagnosed with stage T2–T4 prostate cancer with no evidence of metastases, who had not previously undergone bisphosphonate treatment or long-term hormone therapy. A total of 508 men were randomized in a 1:1 ratio to receive 2,080 mg of oral sodium clodronate or placebo daily for up to 5 years. Patients were evaluated at 6 weeks after randomization, then every 6 months for 2 years, and yearly thereafter. Median follow-up was 118 months.

The results showed no benefit in bone-metastasis-free survival in the clodronate group compared with the placebo group (80 events vs 68 events, hazard ratio [HR] 1.22, 95% CI 0.88–1.68) or overall survival (130 deaths vs 127 deaths, HR 1.02, 95% CI 0.80–1.30). Clodronate was generally well tolerated, although there were more adverse events reported in the clodronate group than in the placebo group (P = 0.18); patients receiving clodronate required dose modification more often (P = 0.002).

The authors conclude that clodronate should no longer be investigated in the adjuvant setting as a treatment for nonmetastatic prostate cancer, but trials of more potent bisphosphonates should be carried out, for example zoledronic acid which is being assessed in the MRC stampede trial (ISRCTN78818544).