A randomised trial of oral sodium clodronate versus a matching placebo in patients with locally advanced prostatic adenocarcinoma

Can the drug clodronate help to prevent prostate cancer that has not yet spread, from spreading to bones?

What was this study about?

PR04 was a trial for men who were within 3 years after initial diagnosis with prostate cancer and who did not have bone metastases. The aim of this trial was to see whether addition to the standard therapy of a first general bisphosphonate drug called sodium clodronate (Loron520) could delay or prevent the development of symptomatic bone metastases. Consenting patients were therefore randomly assigned to receive either daily oral sodium clodronate or placebo for a maximum of 5 years.

What difference did this study make?

We found no evidence that clodronate helped to prevent the development of metastases. We measured how long it took for some men to develop bone metastases that were causing symptoms. In this study, the group of men receiving clodronate did slightly worse. At 5 years after joining the trial, over 8 out of every 10 men in the clodronate group and nearly 8 in every 10 men in the placebo group had not developed bone metastases that were causing symptoms. Although there is evidence that clodronate is not helpful, we did not have enough information to be sure that clodronate is worse. We found the risk of death was not at all affected by clodronate.

With the help of the men who took part in this trial, we have been able to test this drug thoroughly. The results will help men in the future because clodronate will not be routinely offered to men without metastases. Together with it’s sister trial, this trial did suggest that newer bisphosphonates should be examined for men with high risk prostate cancer. The STAMPEDE trial is doing this.

Type of study

Randomised trial

Contact details

Who funded the study?

Medical Research Council with support from Roche Products Ltd (formerly Boehringer Mannheim [UK])

When did it take place?

Patients were recruited between 1995 and 1998.

Where did it take place?

Hospitals throughout the UK and New Zealand.

Who was included?

Men with non-metastatic prostate cancer.