The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지

Treatment of Bone Metastasis

골 전이 병변의 증상 조절과 치료

  • Cho, Eun-Kyung (Division of Hematooncology, Department of Internal Medicine, School of Medicine, Gachon University of Medicine and Science)
  • 조은경 (가천의과학대학교 의학전문대학원 내과학교실 혈액종양내과)
  • Published : 2011.09.01
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Abstract

The bone is a very common site of metastasis in patients with advanced cancer. Bone metastases can cause a wide range of symptoms and complications, such as pain, pathologic fractures, spinal cord compression, and hypercalcemia. The aim of treatment is to reduce the risk of skeletal related events, which in turn can increase quality of life and life expectancy. The main therapeutic alternatives directed at treating bone metastases in advanced cancer have been orthopedic stabilization, radiotherapy, bisphosphonates, and radioisotope treatment, in conjunction with chemotherapy or hormonal therapy. Drugs used for pain relief include non-opioid analgesics, opioid, and adjuvant analgesics. Most patients require a combination of medications for optimal pain relief. It has been demonstrated that single-fraction radiotherapy with $1\;{\times}\;8$ Gy is as effective for pain relief as multi-fraction regimens. Painful bone metastasis with pathologic fracture or spinal cord compression should be treated with multi-fraction long-course radiotherapy. Denosumab, a new generation of bone metastasis treatment, is a fully human monoclonal antibody that inhibits osteoclast maturation, activation, and function by binding to receptor activator of nuclear factor kappa B ligand, with the final result being a reduced rate of bone resorption.

Keywords

References

  1. Coleman RE. Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006;12:6243s-6249s. https://doi.org/10.1158/1078-0432.CCR-06-0931
  2. Coleman RE, Rubens RD. Bone metastases and breast cancer. Cancer Treat Rev 1985;12:251-270. https://doi.org/10.1016/0305-7372(85)90008-8
  3. Parfitt AM. Bone remodeling, normal and abnormal: a biological basis for the understanding of cancer-related bone disease and its treatment. Can J Oncol 1995;5(Suppl 1):1-10.
  4. Raisz LG. Physiology and pathophysiology of bone remodeling. Clin Chem 1999;45:1353-1358.
  5. Suva LJ, Washam C, Nicholas RW, Griffin RJ. Bone metastasis: mechanisms and therapeutic opportunities. Nat Rev Endocrinol 2011;7:208-218. https://doi.org/10.1038/nrendo.2010.227
  6. Mundy GR. Mechanisms of bone metastasis. Cancer 1997;80(Suppl):S1546-S1556.
  7. Joishy SK, Walsh D. The opioid-sparing effects of intravenous ketorolac as an adjuvant analgesic in cancer pain: application in bone metastases and the opioid bowel syndrome. J Pain Symptom Manage 1998;16:334-339. https://doi.org/10.1016/S0885-3924(98)00081-5
  8. Brown CR, Mazzulla JP, Mok MS, Nussdorf RT, Rubin PD, Schwesinger WH. Comparison of repeat doses of intramuscular ketorolac tromethamine and morphine sulfate for analgesia after major surgery. Pharmacotherapy 1990;10:S45-S50.
  9. Feldman HI, Kinman JL, Berlin JA, et al. Parenteral ketorolac: the risk for acute renal failure. Ann Intern Med 1997;126:193-199. https://doi.org/10.7326/0003-4819-126-3-199702010-00003
  10. Chan FK, Hung LC, Suen BY, et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med 2002;347:2104-2110. https://doi.org/10.1056/NEJMoa021907
  11. Tramadol: a new oral analgesic. Med Lett Drugs Ther 1995;37:59-62.
  12. Warfield CA. Guidelines for routine use of controlled-release oral morphine sulfate tablets. Semin Oncol 1993;20(Suppl 1):S36-S47.
  13. Hagen NA, Babul N. Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlledrelease hydromorphone in the treatment of cancer pain. Cancer 1997;79:1428-1437. https://doi.org/10.1002/(SICI)1097-0142(19970401)79:7<1428::AID-CNCR21>3.0.CO;2-0
  14. Finley RS. Bisphosphonates in the treatment of bone metastases. Semin Oncol 2002;29(Suppl 4):S132-S138.
  15. Berenson JR, Hillner BE, Kyle RA, et al. American society of clinical oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma. J Clin Oncol 2002;20:3719-3736. https://doi.org/10.1200/JCO.2002.06.037
  16. Michaelson MD, Smith MR. Bisphosphonates for treatment and prevention of bone metastases. J Clin Oncol 2005;23:8219-8224. https://doi.org/10.1200/JCO.2005.02.9579
  17. Saad F, Gleason DM, Murray R, et al. A randomized, Placebocontrolled trial of zoledronic acid in patients with hormonerefractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94:1458-1468. https://doi.org/10.1093/jnci/94.19.1458
  18. Saad F, Chen YM, Gleason DM, Chin J. Continuing benefit of zoledronic acid in preventing skeletal complications in patients with bone metastases. Clin Genitourin Cancer 2007;5:390-396. https://doi.org/10.3816/CGC.2007.n.022
  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. https://doi.org/10.1002/cncr.11892
  20. Ruggiero SL, Mehrotra B, Rosenberg TJ, Engroff SL. Osteonecrosis of the jaws associated with the use of bisphosphonates: a review of 63 cases. J Oral Maxillofac Surg 2004;62:527-534. https://doi.org/10.1016/j.joms.2004.02.004
  21. Body JJ. New developments for treatment and prevention of bone metastases. Curr Opin Oncol 2011;23:338-342. https://doi.org/10.1097/CCO.0b013e328347918b
  22. Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study. J Clin Oncol 2010;28:5132-5139. https://doi.org/10.1200/JCO.2010.29.7101
  23. Castellano D, Sepulveda JM, Garcia-Escobar I, Rodriguez-Antolin A, Sundlov A, Cortes-Funes H. The role of RANK-ligand inhibition in cancer: the story of denosumab. Oncologist 2011;16:136-145. https://doi.org/10.1634/theoncologist.2010-0154
  24. Amouzegar-Hashemi F, Behrouzi H, Kazemian A, Zarpak B, Haddad P. Single versus multiple fractions of palliative radiotherapy for bone metastases: a randomized clinical trial in Iranian patients. Curr Oncol 2008;15:151.
  25. Wu JS, Wong RK, Lloyd NS, Johnston M, Bezjak A, Whelan T. Radiotherapy fractionation for the palliation of uncomplicated painful bone metastases: an evidence-based practice guideline. BMC Cancer 2004;4:71. https://doi.org/10.1186/1471-2407-4-71
  26. Wu JS, Wong R, Johnston M, et al. Meta-analysis of dosefractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys 2003;55:594-605. https://doi.org/10.1016/S0360-3016(02)04147-0
  27. Chow E, Harris K, Fan G, Tsao M, Sze WM. Palliative radiotherapy trials for bone metastases: a systematic review. J Clin Oncol 2007;25:1423-1436. https://doi.org/10.1200/JCO.2006.09.5281
  28. Sze WM, Shelley MD, Held I, Wilt TJ, Mason MD. Palliation of metastatic bone pain: single fraction versus multifraction radiotherapy: a systematic review of randomized trials. Clin Oncol (R Coll Radiol) 2003;15:345-352.
  29. Rades D, Schild SE, Abrahm JL. Treatment of painful bone metastases. Nat Rev Clin Oncol 2010;7:220-229. https://doi.org/10.1038/nrclinonc.2010.17
  30. Vassiliou V, Bruland O, Janjan N, Lutz S, Kardamakis D, Hoskin P. Combining systemic bisphosphonates with palliative external beam radiotherapy or bone-targeted radionuclide therapy: interactions and effectiveness. Clin Oncol (R Coll Radiol) 2009;21:665-667. https://doi.org/10.1016/j.clon.2009.07.011
  31. Chow E, Loblaw A, Harris K, et al. Dexamethasone for the prophylaxis of radiation-induced pain flare after palliative radiotherapy for bone metastases: a pilot study. Support Care Cancer 2007;15:643-647. https://doi.org/10.1007/s00520-007-0217-z
  32. Bouza C, Lopez-Cuadrado T, Cediel P, Saz-Parkinson Z, Amate JM. Balloon kyphoplasty in malignant spinal fractures: a systematic review and meta-analysis. BMC Palliat Care 2009;8:12. https://doi.org/10.1186/1472-684X-8-12
  33. Masala S, Massari F, Fiori R, Mammucari M, Bartolucci DA, Simonetti G. Future directions in percutaneous vertebroplasty. Radiol Med 2009;114:976-983. https://doi.org/10.1007/s11547-009-0418-2
  34. Berenson J, Pflugmacher R, Jarzem P, et al. Balloon kyphoplasty versus non-surgical fracture management for treatment of painful vertebral body compression fractures in patients with cancer: a multicentre, randomized controlled trial. Lancet Oncol 2011;12:225-235. https://doi.org/10.1016/S1470-2045(11)70008-0
  35. Robinson RG, Preston DF, Baxter KG, Dusing RW, Spicer JA. Clinical experience with strontium-89 in prostatic and breast cancer patients. Semin Oncol 1993;20(Suppl 2):S44-S48.
  36. Roque I Figuls M, Martinez-Zapata MJ, Scott-Brown M, Alonso-Coello P. Radioisotopes for metastatic bone pain. Cochrane Database Syst Rev 2011:CD003347.
  37. Rades D, Fehlauer F, Schulte R, et al. Prognostic factors for local control and survival after radiotherapy of metastatic spinal cord compression. J Clin Oncol 2006;24:3388-3393. https://doi.org/10.1200/JCO.2005.05.0542
  38. Rades D, Dunst J, Schild S. The first score predicting overall survival in patients with metastatics pinal cord compression. Cancer 2008;112:157-161. https://doi.org/10.1002/cncr.23150
  39. Rades D, Douglas S, Veninga T, et al. Validation and simplification of a score predicting survival in patients irradiated for metastatic spinal cord compression. Cancer 2010;116:3670-3673. https://doi.org/10.1002/cncr.25223
  40. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005;352:373-379. https://doi.org/10.1056/NEJMcp042806