Clinical Reviews in Bone and Mineral Metabolism

, Volume 5, Issue 3, pp 172–177

Bisphosphonates in Advanced Malignant Disease

Original Paper

Abstract

Tumor-induced osteolysis is responsible for a considerable morbidity and often dramatically alters patients’ quality of life. Bone destruction is essentially mediated by the osteoclasts, the formation and activity of which are stimulated by tumor secretory products. Bisphosphonates are able to interrupt the vicious circle between metastatic cancer cells and bone cells/bone matrix by inducing osteoclast apoptosis. For breast cancer patients with metastatic disease and radiographic evidence of bone destruction, current guidelines consist in the administration of either pamidronate 90 mg over 2 h or zoledronic acid 4 mg over 15 min every 3–4 weeks. Other bisphosphonates were not considered. Nevertheless, placebo-controlled trials have established that, when administered over a prolonged period by the oral route (clodronate and ibandronate) or by the intravenous route (pamidronate, ibandronate, and zoledronic acid), bisphosphonates reduce the skeletal morbidity rate by 25–40% in breast cancer metastatic to the skeleton. It has been shown in a 2-year controlled comparative trial between pamidronate and zoledronic acid that this latter compound has a superior efficacy in breast cancer but not in myeloma. Zoledronic acid is also the only bisphosphonate whose activity has been demonstrated in hormone-refractory metastatic prostate cancer. Serum creatinine has to be checked before each zoledronic acid infusion. Lastly, the long-term consequences on bone health of a prolonged therapy with very potent bisphosphonates remain poorly known and some experts prefer to adjust therapy to the individual patient, even more that the recently described cases of osteonecrosis of the jaw appear to be partly due to excessive bisphosphonate therapy.

Keywords

Bisphosphonate Bone metastases Breast cancer Prostate cancer Pain Fracture 

References

  1. 1.
    Plunkett TA, Smith P, Rubens RD. Risk of complications from bone metastases in breast cancer. Implications for management. Eur J Cancer 2000;36:476–82.PubMedCrossRefGoogle Scholar
  2. 2.
    Body JJ. Individualization of bisphosphonates therapy. In: Piccart M, Wood W, Hung M-C, Sol LJ, Cardoso F, editors. Breast cancer management in the era of molecular medicine: towards tailored approaches. Springer-Verlag, Berlin, 2006. p. 545–64.Google Scholar
  3. 3.
    Lipton A. Bisphosphonates and breast carcinoma: present and future. Cancer 2000;88 Suppl 12:3033–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Hortobagyi GN, Theriault RL, Lipton A, for the Protocol 19 Aredia Breast Cancer Study Group. Long-term prevention of skeletal complications of metastatic breast cancer with pamidronate. J Clin Oncol 1998;16:2038–44.Google Scholar
  5. 5.
    Saad F, Gleason DM, Murray R, Tchekmedyian S, et al. Zoledronic Acid Prostate Cancer Study Group. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. Natl Cancer Inst 2004;96:879–82.Google Scholar
  6. 6.
    Melton LJ 3rd, Kyle RA, Achenbach SJ, et al. Fracture risk with multiple myeloma: a population-based study. J Bone Miner Res 2005;20:487–93.PubMedCrossRefGoogle Scholar
  7. 7.
    Kakonen SM, Mundy GR. Mechanisms of osteolytic bone metastases in breast carcinoma. Cancer 2003;97 Suppl 3:834–39.PubMedCrossRefGoogle Scholar
  8. 8.
    Mundy GR. Endothelin-1 and osteoblastic metastasis. Proc Natl Acad Sci USA 2003;100:10588–9.PubMedCrossRefGoogle Scholar
  9. 9.
    Dunstan CR. Osteoprotegerin and osteoprotegerin ligand mediate the local regulation of bone resorption. The Endocrinologist 2000;10:18–26.CrossRefGoogle Scholar
  10. 10.
    Berruti A, Dogliotti L, Tucci M, Tarabuzzi R, et al. Metabolic bone disease induced by prostate cancer: rationale for the use of bisphosphonates. J Urol 2001;166:2023–31.PubMedCrossRefGoogle Scholar
  11. 11.
    Major P, Lortholary A, Hon J, Abdi E, et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001;19:558–67.PubMedGoogle Scholar
  12. 12.
    Body JJ. Hypercalcemia of malignancy. Semin Nephrol 2004;24:48–54.PubMedCrossRefGoogle Scholar
  13. 13.
    Body JJ. Breast cancer: bisphosphonate therapy for metastatic bone disease. Clin Cancer Res 2006;12 Suppl 20:6258–63.CrossRefGoogle Scholar
  14. 14.
    Lipton A, Theriault RL, Hortobagyi GN, et al. Pamidronate prevents skeletal complications and is effective palliative treatment in women with breast carcinoma and osteolytic bone metastases: long term follow-up of two randomized, placebo-controlled trials. Cancer 2000;88:1082–90.PubMedCrossRefGoogle Scholar
  15. 15.
    Jagdev SP, Purohito P, Heatley S, et al. Comparison of the effect of intravenous pamidronate and oral clodronate on symptoms and bone resorption in patients with metastatic bone disease. Ann Oncol 2001;12:1433–8.PubMedCrossRefGoogle Scholar
  16. 16.
    Rosen LS, Gordon D, Kaminski M, et al. Zoledronic acid versus pamidronate in the treatment of skeletal metastases in patients with breast cancer or osteolytic lesions of multiple myeloma: a phase III, double-blind, comparative trial. Cancer J 2001;7:377–87.PubMedGoogle Scholar
  17. 17.
    Rosen LS, Gordon D, Kaminski M, et al. Long-term efficacy and safety of zoledronic acid compared with pamidronate disodium in the treatment of skeletal complications in patients with advanced multiple myeloma or breast carcinoma: a randomized, double-blind, multicenter, comparative trial. Cancer 2003;98:1735–44.PubMedCrossRefGoogle Scholar
  18. 18.
    Body JJ. Treatment and prevention of bone metastases and myeloma bone disease. In: Primer on the metabolic bone diseases and disorders of mineral metabolism. The American Society for Bone and Mineral Research, Washington DC, 6th ed. 2006. p. 383–90.Google Scholar
  19. 19.
    Rosen LS, Gordon DH, Dugan W Jr, et al. Zoledronic acid is superior to pamidronate for the treatment of bone metastases in breast carcinoma patients with at least one osteolytic lesion. Cancer 2004;100:36–43.PubMedCrossRefGoogle Scholar
  20. 20.
    Body JJ, Diel IJ, Lichinitser MR, et al. MF 4265 Study Group. Intravenous ibandronate reduces the incidence of skeletal complications in patients with breast cancer and bone metastases. Ann Oncol 2003;14:1399–405.Google Scholar
  21. 21.
    Body JJ, Diel IJ, Lichinitzer M, et al. Oral ibandronate reduces the risk of skeletal complications in breast cancer patients with metastatic bone disease: results from two randomized, placebo-controlled phase III studies. Br J Cancer 2004;90:1133–7.PubMedCrossRefGoogle Scholar
  22. 22.
    Kohno N, Aogi K, Minami H, et al. Zoledronic acid significantly reduces skeletal complications compared with placebo in Japanese women with bone metastases from breast cancer: a randomized, placebo-controlled trial. J Clin Oncol 2005;23:3314–21.PubMedCrossRefGoogle Scholar
  23. 23.
    Body JJ. Bisphosphonates for malignancy-related bone disease: current status, future developments. Support Care Cancer 2006;14:408–18.PubMedCrossRefGoogle Scholar
  24. 24.
    Saad F, Gleason DM, Murray R, et al. Zoledronic Acid Prostate Cancer Study Group. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458–68.PubMedGoogle Scholar
  25. 25.
    Mancini I, Dumon JC, Body JJ. Efficacy and safety of ibandronate in the treatment of opioid-resistant bone pain associated with metastatic bone disease: a pilot study. J Clin Oncol 2004;22:3587–92.PubMedCrossRefGoogle Scholar
  26. 26.
    Body JJ. Dosing regimens and main adverse events of bisphosphonates. Semin Oncol 2001;28 Suppl 11:49–53.PubMedCrossRefGoogle Scholar
  27. 27.
    Chang JT, Green L, Beitz J. Renal failure with the use of zoledronic acid. N Engl J Med 2003;349:1676–9.PubMedCrossRefGoogle Scholar
  28. 28.
    Ruggiero SL, Mehrotra B, Rosenberg TJ, et al. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62:527–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Bamias A, Kastritis E, Bamia C, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005;23:8580–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Woo SB, Hellstein JW, Kalmar JR. Bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006;144:753–61.PubMedGoogle Scholar
  31. 31.
    Migliorati C, Casiglia J, Epstein J, et al. Managing the care of patients with bisphosphonate-associated osteonecrosis. JADA 2005;136:1658–68.PubMedGoogle Scholar
  32. 32.
    Hillner BE, Ingle JN, Chlebowski RT, et al. American Society of Clinical Oncology. American Society of Clinical Oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol 2003;21:4042–57Google Scholar
  33. 33.
    Mashiba T, Hirano T, Turner CH, et al. Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib. J Bone Miner Res 2000;15:613–20.PubMedCrossRefGoogle Scholar
  34. 34.
    Brown JE, Thomson CS, Ellis SP, et al. Bone resorption predicts for skeletal complications in metastatic bone disease. Br J Cancer 2003;89:2031–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Coleman RE, Major P, Lipton A, et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid. J Clin Oncol 2005;23:4925–35.PubMedCrossRefGoogle Scholar
  36. 36.
    Body JJ, Facon T, Coleman RE, et al. A study of the biologic receptor activator of nuclear factor-kB ligand inhibitor, Denosumab (AMG 162), in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 2006;12:1221–8.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  1. 1.Department of MedicineCHU Brugmann and Institut J. Bordet, Université Libre de Bruxelles (U.L.B.)BruxellesBelgium

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