An article published Online First and in an upcoming edition of The Lancet Oncology reports that oral sodium clodronate improves overall survival in men with advanced prostate cancer. However it does not reduce the risk of death in men with localised disease. These are the final results of the MRC PR05 and MRC PR04 trials.
Frequently, prostate cancer spreads to the bone. Bisphosphonates, such as sodium clodronate, is a group of drugs that prevent the loss of bone mass. For that reason there is indication that this type if drug might improve the outcomes of patients with advanced prostate cancer.
Two UK-led trials started in 1994 to observe the effect of sodium clodronate in men with advanced or localised prostate cancer. The first one included 311 men with advanced prostate cancer. They were all starting or responding to hormone therapy which is standard care for bone metastases. They were randomly allocated to take oral sodium clodronate or placebo for up to three years. The second trial included 508 men with localised prostate cancer who were receiving standard care which is usually treatment with radiotherapy, hormone therapy, or both. They were randomly allocated to take oral sodium clodronate or placebo for up to five years. The principal results of the original trials showed that men with advanced disease had a reduction in the development of symptomatic bone metastases and some improvement in overall survival. However, men with localised disease showed no improvement in overall survival or interruption in the spread of cancer.
Matthew Sydes from the Medical Research Council Clinical Trials Unit in the UK and collaborators recorded in the study the long-term survival outcomes of patients involved in both of the initial trials.
In the group treated with clodronate, findings showed a 23 percent relative decrease in death. In the same group, overall survival was 30 percent after five years, and 17 percent after ten years. In the placebo group, results were 21 percent and 9 percent respectively.
In men with localised disease, clodronate showed no benefit in overall survival. After five years, overall survival was 78 percent in patients given clodronate and 80 percent in patients given placebo. After ten years, survival in general was 48 percent in comparision to 51 percent in the placebo group.
They authors explain: “PR05 is the first trial, to our knowledge, to show an overall survival benefit conferred by an oral bisphosphonate when given in addition to standard hormone therapy to men with bone metastases who are starting or responding to hormone therapy. However, there is no evidence that clodronate is of any benefit when given as an adjuvant to treatment in men with non-metastatic prostate cancer.”
“Adjuvant therapy with oral sodium clodronate in locally advanced and metastatic prostate cancer: long-term overall survival results from the MRC PR04 and PR05 randomised controlled trials”
David P Dearnaley, Malcolm D Mason, Mahesh K B Parmar, Karen Sanders, Matthew R Sydes
DOI: 10.1016/S1470-2045(09)70201-3
Written by Stephanie Brunner (B.A)