Radiopharmaceuticals for the Therapy of Metastatic Bone Pain

뼈전이의 방사성동위원소 통증치료

  • Ahn, Byeong-Cheol (Department of Nuclear Medicine, Kyungpook National University Medical School and Kyungpook National University Hospital)
  • 안병철 (경북대학교 의과대학 핵의학교실)
  • Published : 2006.04.29

Abstract

Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life it occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and its complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesions. $^{32}P,\;^{89}SrCl,\;^{153}Sm-EDTMP,\;^{188}Re/^{186}Re-HEDP,\;and\;^{177}Lu-EDTMP$ can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic form of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and, in some studios, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article illustrates the salient features of these radiopharmaceuticals, including the usual therapuetic dose, method of administration, and indications for use and also describe about the pre-management checklists, and jndication/contraindication and follow-up protocol.

Keywords

References

  1. Finlay IG, Mason MD, Shelley M. Radioisotopes for the palliation of metastatic bone cancer: a systematic review. Lancet oncol 2005;6:392-400 https://doi.org/10.1016/S1470-2045(05)70206-0
  2. Pandit-Taskar N, Batraki M, Divgi CR. Radiopharmaceutical therapy for palliation of bone pain from osseous metastases. J Nucl Med 2004;45:1358-65
  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;45:1353-8
  5. Lipton A, Costa L, Ali SM, Demers LM. Bone markers in the management of metastatic bone disease. Cancer Treat Rev 2001;27:181-5 https://doi.org/10.1053/ctrv.2000.0212
  6. Honore P, Rogers SD, Schwei MJ, et al. Murine models of inflammatory, neuropathic and cancer pain each generates a unique set of neurochemical changes in the spinal cord and sensory neurons. Neuroscience 2000;98:585-98 https://doi.org/10.1016/S0306-4522(00)00110-X
  7. Treede RD, Meyer RA, Raja SN, Campbell JN. Peripheral and central mechanisms of cutaneous hyperalgesia. Prog Neurobiol 1992;38:397-421 https://doi.org/10.1016/0301-0082(92)90027-C
  8. Mantyh PW, Clohisy DR, Koltzenburg M, Hunt SP. Molecular mechanisms of cancer pain. Nat Rev Cancer 2002;2:201-9 https://doi.org/10.1038/nrc747
  9. Urch C. The pathophysiology of cancer-induced bone pain: current understanding. Palliat Med 2004;18:267-74 https://doi.org/10.1191/0269216304pm887ra
  10. Serafini AN. Therapy of metastatic bone pain. J Nucl Med 2001;42:895-906
  11. World Health Organization. Cancer Pain Relief and Palliative Care: Report of a WHO Expert Committee. Geneva, Switzerland: World Health Organization; 1990
  12. LoRusso P. Analysis of skeletal-related events in breast cancer and response to therapy. Semin Oncol 2001;28(4 suppl 11):22-27
  13. McCloskey EV, MacLennan I, Drayson M, Chapman C, Dunn J, Kanis JA. Effect of clodronate on morbidity and mortality in myelomatosis. Br J Haematol 1998;100:317-25 https://doi.org/10.1046/j.1365-2141.1998.00567.x
  14. Powles TS, Paterson S, Kanis JA, et al. Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer. J Clin Oncol 2002;20:3219-24 https://doi.org/10.1200/JCO.2002.11.080
  15. Friedland J. Local and systemic radiation for palliation of metastatic disease. Urol Clin North Am 1999;26:391-402 https://doi.org/10.1016/S0094-0143(05)70078-1
  16. Blitzer PH. Reanalysis of the RTOG study of the palliation of symptomatic osseous metastases. Cancer 1985;55:1468- 72 https://doi.org/10.1002/1097-0142(19850401)55:7<1468::AID-CNCR2820550708>3.0.CO;2-M
  17. Epstein M, Stewart BH, Antunez AR, et al. Half and total body irradiation for carcinoma of the prostate. J Urol. 1979;122:330-2 https://doi.org/10.1016/S0022-5347(17)56391-0
  18. Hoskin PJ. Radiotherapy in the management of bone pain. Clin Orthop 1995;312:105-19
  19. Salazar OM, Rubin P, Hendrickson FR, et al. Single dose half body irradiation for palliation of multiple bone metastases from solid tumors. Cancer 1986;58:29-36 https://doi.org/10.1002/1097-0142(19860701)58:1<29::AID-CNCR2820580107>3.0.CO;2-2
  20. Steenland E, Lee J, van Houwelingen H, et al. The effect of single fraction compared to multiple fractions in painful bone metastases: a global analysis of the Dutch Bone Metastasis Study. Radiat Oncol 1999;52:101-9 https://doi.org/10.1016/S0167-8140(99)00110-3
  21. Hoskin PJ, Ford HT, Harmer CL. Hemibody irradiation for metastatic bone pain in two histologically distinct groups of patients. Clin Pathol 1991;1:67-9
  22. Hoskin PJ, Stratford MRL, Folkes LK, Regan J, Yarnold JR. Effect of local radiotherapy for bone pain on urinary markers of osteoclast activity. Lancet 2000;355:1428-9 https://doi.org/10.1016/S0140-6736(00)02144-9
  23. Tannock I. Is there evidence that chemotherapy is of benefit to patients with carcinoma of the prostate? J Clin Oncol 1985;3:1013-21 https://doi.org/10.1200/JCO.1985.3.7.1013
  24. Robinson RG, Blake GM, Preston DF, et al. Strontium-89:treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone. Radiographics 1989;9:271-81 https://doi.org/10.1148/radiographics.9.2.2467331
  25. Blake GM, Zivanovic MA, McEwan AJ, et al. Sr-89 therapy:strontium kinetics in disseminated carcinoma of the prostate. Eur J Nucl Med 1986;12:447-54
  26. Laing AH, Ackery DM, Bayly RJ, et al. Strontium-89 chloride for pain palliation in prostatic skeletal malignancy. Br J Radiol 1991;64:816-22 https://doi.org/10.1259/0007-1285-64-765-816
  27. Mertens WC, Stitt L, Porter AT. Strontium 89 therapy and relief of pain in patients with prostatic carcinoma metastatic to bone: a dose response relationship- Am J Clin Oncol 1993;16:238-42 https://doi.org/10.1097/00000421-199306000-00009
  28. Kasalicky J, Krajska V. The effect of repeated strontium-89 chloride therapy on bone pain palliation in patients with skeletal cancer metastases. Eur J Nucl Med 1998;25:1362-7 https://doi.org/10.1007/s002590050309
  29. Dafermou A, Colamussi P, Giganti M, et al. A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur J Nucl Med 2001;28:788-98 https://doi.org/10.1007/s002590100533
  30. Buchali K, Correns HJ, Schuerer M, et al. Results of a double blind study of 89-strontium therapy of skeletal metastases of prostatic carcinoma. Eur J Nucl Med 1988;14: 349-51
  31. Tu S, Millikan RE, Mengistu B, et al. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet 2001;357:336-41 https://doi.org/10.1016/S0140-6736(00)03639-4
  32. O'Sullivan JM, McCready VR, Flux G, et al. High activity Rhenium-186 HEDP with autologous peripheral blood stem cell rescue: a phase I study in progressive hormone refractory prostate cancer metastatic to bone. Br J Cancer 2002;86:1715-20 https://doi.org/10.1038/sj.bjc.6600348
  33. Dickie GJ, Macfarlane D. Strontium and samarium therapy for bone metastases from prostate carcinoma. Australas Radiol 1999;43:476-9 https://doi.org/10.1046/j.1440-1673.1999.00716.x
  34. Nair N. Relative efficacy of $^{32}$P and $^{89}$Sr in palliation in skeletal metastases. J Nucl Med 1999;40:256-61
  35. Sciuto R, Festa A, Pasqualoni R, et al. Metastatic bone pain palliation with 89-Sr and 186-Re-HEDP in breast cancer patients. Breast Cancer Res Treat 2001;66:101-9 https://doi.org/10.1023/A:1010658522847
  36. Liepe K, Franke WG, Kropp J, et al. Comparison of rhenium-188, rhenium-186-HEDP and strontium-89 in palliation of painful bone metastases. Nuklearmedizin 2000; 39:146-51 https://doi.org/10.1055/s-0038-1632262
  37. Eary JF, Collins C, Stabin M, et al. Samarium-153-EDTMP biodistribution and dosimetry estimation. J Nucl Med 1993;34:1031-6
  38. Anderson PM, Wiseman GA, Dispenzieri A, et al. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol 2002;20:189-96 https://doi.org/10.1200/JCO.20.1.189
  39. Turner JH, Claringbold PG. A phase II study of treatment of painful multifocal skeletal metastases with single and repeated dose samarium-153 ethylenediaminetetramethylene phosphonate. Eur J Cancer 1991;27:1084-6 https://doi.org/10.1016/0277-5379(91)90297-Q
  40. Serafini AN, Houston SJ, Resche I, et al. Palliation of pain associated with metastatic bone cancer using samarium-153 lexidronam: a double-blind placebo-controlled clinical trial. J Clin Oncol 1998;16:1574-81 https://doi.org/10.1200/JCO.1998.16.4.1574
  41. Dafermou A, Colamussi P, Giganti M, Cittanti C, Bestagno M, Piffanelli A. A multicentre observational study of radionuclide therapy in patients with painful bone metastases of prostate cancer. Eur J Nucl Med 2001;28:788-98 https://doi.org/10.1007/s002590100533
  42. Han SH, Zonneberg BA, de Klerk JM, et al. $^{186}$Re -etidronate in breast cancer patients with metastatic bone pain. J Nucl Med 1999;40:639-42
  43. Liepe K, Hliscs R, Kropp J, et al. Dosimetry of $^{188}$Rehydroxyethylidene diphosphonate in human prostate cancer skeletal metastases. J Nucl Med 2003;44:953-60
  44. Palmedo H, Manka-Waluch A, Albers P, et al. Repeated bone targeted therapy for hormone-refractory prostate carcinoma: randomized phase II trial with the new, high- energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate. J Clin Oncol 2003;21:2869-75 https://doi.org/10.1200/JCO.2003.12.060
  45. Srivastava SC, Atkins HL, Krishnamurthy GT, et al. Treatment of metastatic bone pain with tin-117m stannic diethylenetriaminepentaacetic acid: a phase I/II clinical study. Clin Cancer Res 1998;4:61-8
  46. Schraml FV, Parr LF, Ghurani S, Silverman ED. Autopsy of a cadaver containing strontium-89-chloride. J Nucl Med 1997;38: 380-2
  47. Papatheofanis FJ. Quantitation of biochemical markers of bone resorption following strontium-89 chloride therapy for metastatic prostate carcinoma. J Nucl Med 1997;38:1175-9
  48. Papatheofanis FJ. Serum PICP as a bone formation marker in 89Sr and external beam radiotherapy of prostatic bony metastasis. Br J Radiol 1997;70:594-8 https://doi.org/10.1259/bjr.70.834.9227252