Guidelines:Prostate cancer/Management/Locally advanced and metastatic/Bisphosphonates

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Management of locally advanced and metastatic prostate cancer > Guidelines:Prostate cancer/Management/Locally advanced and metastatic/Bisphosphonates

Bisphosphonates

Bone is the most frequent site for metastases from prostate cancer. It has been estimated that 85% of men with advanced prostate cancer, particularly when the disease is not controlled by androgen deprivation therapy, will have bony metastases. These metastases lead to bone pain, pathological fractures, spinal cord compression and in rare instances, disturbances in serum calcium levels sufficient to produce symptoms. This composite of bone complications associated with cancer has been encompassed by the term ‘skeletal related events’ (SRE). Bisphosphonates have been shown to be effective in reducing the incidence of SREs in myeloma and breast cancer.[1][2][3]

Although prostate cancer usually results in sclerotic or osteoblastic lesions, there is evidence of the presence of an osteolytic component and this may be inhibited by bisphosphonates.[4][5][6][7]

This section examines the evidence for the use of bisphosphonates in the prevention of SRE and bone pain control in men with metastatic prostate cancer.

There are two points regarding bisphosphonates and prostate cancer worth clarifying. First, the use of bisphosphonates to prevent prostate cancer associated SREs is distinct from discussions about the management of osteoporosis induced by therapies used to treat prostate cancer. Namely, androgen deprivation can lead to a decrease in bone mineral density and in some cases, osteoporotic crush fractures. The relevance of this is paramount in the adjuvant setting, and the dosing and schedules of bisphosphonates are far lower than the doses for prevention of SREs. This matter is not addressed in this review. The second point to appreciate when reviewing the following dataset is that bisphosphonates have vastly different potencies. This variability probably leads to the heterogeneity in the outcomes and contributes to the limitations of the recommendations based on the current dataset.


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References

  1. Theriault RL, Lipton A, Hortobagyi GN, Leff R, Glück S, Stewart JF, et al. Pamidronate reduces skeletal morbidity in women with advanced breast cancer and lytic bone lesions: a randomized, placebo-controlled trial. Protocol 18 Aredia Breast Cancer Study Group. J Clin Oncol 1999 Mar;17(3):846-54 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10071275.
  2. Hortobagyi GN, Theriault RL, Porter L, Blayney D, Lipton A, Sinoff C, et al. Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group. N Engl J Med 1996 Dec 12;335(24):1785-91 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8965890.
  3. Coleman RE. Should bisphosphonates be the treatment of choice for metastatic bone disease? Semin Oncol 2001 Aug;28(4 Suppl 11):35-41 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11544574.
  4. Clarke NW, Holbrook IB, McClure J, George NJ. Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study. Br J Cancer 1991 Mar;63(3):420-3 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/2003984.
  5. Percival RC, Urwin GH, Harris S, Yates AJ, Williams JL, Beneton M, et al. Biochemical and histological evidence that carcinoma of the prostate is associated with increased bone resorption. Eur J Surg Oncol 1987 Feb;13(1):41-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/3102281.
  6. Taube T, Kylmälä T, Lamberg-Allardt C, Tammela TL, Elomaa I. The effect of clodronate on bone in metastatic prostate cancer. Histomorphometric report of a double-blind randomised placebo-controlled study. Eur J Cancer 1994;30A(6):751-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/7917532.
  7. Fernández-Conde M, Alcover J, Aaron JE, Ordi J, Carretero P. Skeletal response to clodronate in prostate cancer with bone metastases. Am J Clin Oncol 1997 Oct;20(5):471-6 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/9345330.

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