(Journal of the National Cancer Institute) -- Oral sodium clodronate may slow the development of symptomatic bone metastases and reduce the risk of death in men with advanced prostate cancer, according to a randomized controlled trial in the September 3 issue of the Journal of the National Cancer Institute.

Prostate cancer spreads most commonly to the bone, and bone metastases affect at least 85% of men with advanced prostate cancer. Bisphosphonates, including sodium clodronate, reduce bone loss. In the early 1990s, researchers in the United Kingdom initiated two phase III trials to examine the benefit of bisphosphonates in men with advanced prostate cancer. The results of one of these trials is now being reported.

David P. Dearnaley, M.D., of the Institute of Cancer Research and Royal Marsden Hospital in Sutton, United Kingdom; Matthew R. Sydes, M.Sc., of the Medical Research Council Clinical Trials Unit in London; and their colleagues randomly assigned 311 men who were starting or responding to hormone therapy for bone metastases to receive either oral sodium clodronate or a placebo for up to 3 years.

After approximately 5 years of follow up, men in the active treatment group had a 21% reduction in the risk of symptomatic bone progression and a 20% reduction in the risk of death, compared with men in the placebo group. However, these findings were not statistically significant. The authors note several limitations to the study, such as the small population size and the use of an oral rather than an intravenous bisphosphonate. Oral bisphosphonates are poorly absorbed by the body.

Patients in the sodium clodronate group did have a statistically significant 29% increase in the time before their performance status deteriorated. However, men who received sodium clodronate had a 71% greater risk of side effects. These effects were reversed when the drug dose was modified. A subgroup analysis suggested that clodronate might be more effective in men with more recently diagnosed disease.

"Further data are needed that reflect the availability of the newer, more potent bisphosphonates as well as the changing patterns of care for men with prostate cancer," the authors write, adding that more research will help to identify appropriate patient populations for treatment and to determine the appropriate type, dose, and duration of bisphosphonate therapy. Preliminary results from the parallel study should be available next year.

In an accompanying editorial, Fred Saad, M.D., of the University of Montreal Hospital Center in Canada, says that although the current findings are not statistically significant, they provide "at least some evidence that starting bisphosphonates earlier in the metastatic state may give better results."