An article published Online First and in an upcoming edition of The Lancet Oncology reports that an oral bisphosphonate, sodium clodronate, improves overall survival in men with advanced prostate cancer. However, it does not reduce the risk of death in men with localized disease. These are the final results of the MRC PR05 and MRC PR04 trials.
One of the most common targets for metastasizes in prostate cancer is the bone. Bisphosphonates are used to mediate the negative effects of hormone therapy, the most common used in the treatment of prostate cancer is Zometa. There are alternative less used bisphosphonate type drugs such as s sodium clodronate. Bisphosphonates are a group of drugs that are designed to prevent the loss of bone mass and make the bone environment less conducive to the development of bone mets. The overall goal of their use is to improve the outcomes of patients with advanced prostate cancer.
Two UK-led trials, MRC PR05 and MRC PR04, started in 1994 to observe the effect of the bisphosphonate sodium clodronate in men with advanced or localized 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 localized 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, not usually found in trials of other bisphosphonates. However, men with localized disease showed no improvement in overall survival or interruption in disease progression.
1- The group treated with clodronate, showed a 23% relative decrease in death. In the same group, overall survival was 30% after five years, and 17% after ten years. In the placebo group, results were 21% and 9% respectively.
2- In men with localized disease, clodronate showed no benefit in overall survival. After five years, overall survival was 78% in patients given clodronate and 80% in patients given placebo. After ten years, survival in general was 48% in comparison to 51% in the placebo group.
According to the authors of the study, the PR05 trial is the first trial 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
The Lancet Oncology
Joel T. Nowak, M.A., M.S.W.