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Management of Painful Bone Metastases: The Interaction between Radiation Therapy and Zoledronate

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DOI: 10.4236/jct.2011.25094    3,688 Downloads   7,411 Views   Citations


Background: Advanced cancers frequently metastasize to bone, and the presence of bone metastases is the most common cause of cancer-related pain. Pain management requires a multidisciplinary approach that involves the use of analgesics, bisphosphonates, radiotherapy, chemotherapy, surgery. The aim of our study was to evaluate the enhancement of radiotherapy on painful bone metastases in patients treated also with bisphosphonates. Materials and Methods: We analyzed the differences in benefit on pain and on quality of life comparing two groups of treatment. The first group comprised 104 patients treated with Radiotherapy (RT), the second one included 50 patients treated with radiotherapy associated to zoledronic acid (RT + Z). All patients completed before, during and after treatment, a questionnaire that rated the grade of pain, the pharmacological type of analgesic therapy and patient’s performance status. For each patient a total score was calculated, from a minimum value of 0% to a maximum of 20%, then expressed as a percentage. Patients were classified as responder if at the follow-up reported a reduction of over 20% of the initial score, no-change if there was a reduction of between 0% and 20%, progression if there was an increasing of the score. Results: In the group RT + Z we found fewer patients that started radiation therapy with severe pain (16% vs 32%), no patient had pain of grade 10, and a higher proportion of asymptomatic patients (12% vs 4%) was observed. In the RT alone group a higher percentage of patients started treatment assuming strong opioid more than once a day (26% vs 24%) and a reduction in number of these patients was about 14% compared with the reduction of 23.6% observed in the group RT + Z. Furthermore an increased total score was calculated only in the 6% of patient belonged to group RT alone. Finally, in the group RT + Z responder patients are 52%, compared to 36% of the RT group, non-responder were 36% versus 60% in the RT. The risk of adverse events (Pz) in the RT + Z was Pz = 0.36, with an odds (Oz) equal to 0.56, while the risk of adverse events (Pc) in the RT group was Pc = 0.60 with an odds (OC) of 1.5. The odds ratio was OR = 0.37, showing a value in favor of treatment RT + Z. Conclusions: In our retrospective observational study it is relevant a clear potentiation of benefit effects related to palliative radiation therapy in patients receiving also bisphosphonate therapy, so obtaining a better control over pain, a decreased need for pain relief and consequently an improved quality of life.

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The authors declare no conflicts of interest.

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R. Franco, M. Calvanese, M. Cuomo, R. Manzo, P. Murino, S. Cappabianca and V. Ravo, "Management of Painful Bone Metastases: The Interaction between Radiation Therapy and Zoledronate," Journal of Cancer Therapy, Vol. 2 No. 5, 2011, pp. 697-702. doi: 10.4236/jct.2011.25094.


[1] R. G. Twycross and S. Fairfield, “Pain in Far-Advanced Cancer,” Pain, Vol. 14, No. 3, 1982, pp. 303-310. doi:10.1016/0304-3959(82)90137-3
[2] J. N. Morris, V. Mor, R. J. Goldberg, S. Sherwood, D. S. Greer and J. Hiris, “The Effect of Treatment Setting and Patient Characteristics of Pain in Terminal Cancer Patients: A Report from the National Hospice Study,” Journal of Chronic Diseases, Vol. 39, No. 1, 1986, pp. 27-35. doi:10.1016/0021-9681(86)90104-9
[3] F. J. Brescia, D. Adler, G. Gray, M. A. Ryan and J. M. Cimino, “Hospitalized Advanced Cancer Patients: A Profil,” Journal of Pain Symptom Manage, Vol. 5, No. 4, 1990, pp. 221-227. doi:10.1016/0885-3924(90)90015-C
[4] A. J. Nora, “Radiation for Bone Metastases,” Cancer, Vol. 80, No. S8, 1997, pp. 1628-1645. doi:10.1002/(SICI)1097-0142(19971015)80:8+<1628::AID-CNCR13>3.0.CO;2-1
[5] S. Mercadante, “Malignant Bone Pain: Pathophysiology and Treatment,” Pain, Vol. 69, No. 1, 1997, pp. 1-18. doi:10.1016/S0304-3959(96)03267-8
[6] P. J. Hoskin, “Bisphosphonates and Radiation Therapy for Palliation of Metastatic Bone Disease,” Cancer Treatment Reviews, Vol. 29, No. 4, 2003, pp. 321-327. doi:10.1016/S0305-7372(03)00013-6
[7] G. Arcangeli, G. Giovinazzo, B. Saracino, L. D’Angelo, G. Giannarelli, G. Arcangeli and A. Micheli, “Radiation Therapy in the Management of Symptomatic Bone Metastases: The Effect of Total Dose and Histology on Pain Relief and Response Duration,” International Journal of Radiation Oncology, Vol. 42, No. 5, 1998, pp. 1119-1126. doi:10.1016/S0360-3016(98)00264-8
[8] G. R. Mundy, “Bone Resorption and Turnover in Health and Disease,” Bone, Vol. 8, 1987, pp. S9-S16.
[9] H. Hsu, D. L. Lacey, C. R. Dunstan, I. Solovyev, A. Colombero, E. Timms, H. L. Tan, G. Elliott, M. J. Kelley, I. Sarosi, L. Wang, X. Z. Xia, R. Elliott, L. Chiu, T. Black, S. Scully, C. Capparelli, S. Morony, G. Shimamoto, M. B. Bass and W. J. Boyle, “Tumour Necrosis Factor Receptor Family Member RANK Mediates Osteoclast Differentiation and Activation Induced by Osteoprotegerin Ligand,” Proceedings of the National Academy of Sciences of the USA, Vol. 96, No. 7, 1999, pp. 3540-3545. doi:10.1073/pnas.96.7.3
[10] W. S. Simonet, D. L. Lacey, C. R. Dunstan, M. Kelley, M. S. Chang, R. Luthy, H. Q. Nguyen, S. Wooden, L. Bennett, T. Boone, G. Shimamoto, M. DeRose, R. Elliott, A. Colombero, H. L. Tan, J. Sullivan, E. Davy, N. Bucay, L. Renshaw-Gegg, T. M. Hughes, D. Hill, W. Pattison, P. Campbell, S. Sander, G. Van, J. Tarpley, P. Derby, R. Lee and W. J. Boyle, “Osteoprotegerin: A Novel Secreted Protein Involved in the Regulation of Bone Density,” Cell, Vol. 89, No. 2, 1997, pp. 309-319. doi:10.1016/S0092-8674(00)80209-3
[11] T. A. Guise, J. J. Yin, R. J. Thomas, M. Dallas, Y. Cui and M. T. Gillespie, “Parathyroid Hormone-Related Protein (PTHrP)(1-139) Isoform is Efficiently Secreted in Vitro and Enhances Breast Cancer Metastasis to Bone in Vivo,” Bone, Vol. 30, No. 5, 2002, pp. 670-676. doi:10.1016/S8756-3282(02)00685-3
[12] P. J. Hoskin, M. R. Stratford, L. K. Folkes, J. Regan and J. R. Yarnold, “Effect of Local Radiotherapy for Bone Pain on Urinary Markers of Osteoclast Activity,” Lancet, Vol. 355, No. 9213, 2000, pp. 1428-1429. doi:10.1016/S0140-6736(00)02144-9
[13] H. S. Poulson, O. S. Nielsen, M. Klee and M. Rorth, “Palliative Irradiation of Bone Metastases,” Cancer Treatment Reviews, Vol. 16, No. 1, 1989, pp. 41-48. doi:10.1016/0305-7372(89)90003-0
[14] P. J. Hoskin, “Radiotherapy in the Management of Bone Pain,” Clinical Orthopaedics and Related Research, Vol. 312, No. 1, 1995, pp. 105-119.
[15] E. Coleman-Robert, “Management of Bone Metastases,” The Oncologist, Vol. 5, No. 6, 2000, pp. 465-466.
[16] S. G. Senaratne, G. Pirianov, J. L. Mansi, T. R. Arnett and K. W. Colston, “Bisphosphonates Induce Apoptosis in Human Breast Cancer Cell Lines,” British Journal of Cancer, Vol. 82, No. 8, 2000, pp. 366-371.
[17] S. P. Jagdev, R. E. Coleman, C. M. Shipman, H. A. Rostami and P. I. Croucher, “The Bisphosphonate, Zoledronic Acid, Induces Apoptosis of Breast Cancer Cells: Evidence for Synergy with Paclitaxel,” British Journal of Cancer, Vol. 84, No. 8, 2001, pp. 1126-1134. doi:10.1054/bjoc.2001.1727
[18] M. V. Lee, E. M. Fong, F. R. Singer and R. S. Guenette, “Bisphosphonate Treatment Inhibits the Growth of Prostate Cancer Cells,” Cancer Research, Vol. 61, No. 6, 2001, pp. 2602-2608.
[19] C. Riebeling, A. M. Forsea, M. Raisova, C. E. Orfanos and C. C. Geilen, “The Bisphosphonate Pamidronate Induces Apoptosis in Human Melanoma Cells in Vitro,” British Journal of Cancer, Vol. 87, No. 3, 2002, pp. 366-371. doi:10.1038/sj.bjc.6600476
[20] P. S. Mackie, J. L. Fisher, H. Zhou and P. F. Choong, “Bisphosphonates Regulate Cell Growth and Gene Expression in the UMR 106-101 Clonal Rat Osteosarcoma Cell Line,” British Journal of Cancer, Vol. 84, No. 7, 2001, pp. 951-958. doi:10.1054/bjoc.2000.1679
[21] C. M. Shipman, P. I. Croucher, R. G. Russell, M. H. Helfrich and M. J. Rogers, “The Bisphosphonate Incadronate (YM175) Causes Apoptosis of Human Myeloma Cells in Vitro by Inhibiting the Mevalonate Pathway,” Cancer Research, Vol. 58, No. 23, 1998, pp. 5294-5297.
[22] A. Ugur-Ural, F. Avcu and Y. Baran, “Bisphosphonate Treatment and Radiotherapy in Metastatic Breast Cancer,” Medical Oncology, Vol. 25, No. 3, 2008, pp. 350-355. doi:10.1007/s12032-008-9044-4
[23] R. Krempiem, P. E. Huber, W. Harms, M. Treiber, M. Wannenmacher and B. Krempiem, “Combination of Early Bisphosphonates Administration and Irradiation Leads to Improved Remineralization and Restabilization of Osteolytic Bone Metastases in an Animal Tumor Model,” Cancer, Vol. 98, No. 6, 2003, pp. 1318-1324. doi:10.1002/cncr.11646
[24] V. Kouloulias, G. Matsopoulos, J. Kouvaris, C. Dardoufas, A. Bottmley, M. Varela, N. Uzunoglu, C. Antypas, A. Metafa, A. Moulopoulos, P. Sandilos and L. Vlahos, “Radiotherapy in Conjunction with Intravenous Infusion of 180 mg Ofsodium Pamidronate in Management of Osteolytic Metastases from Breast Cancer: Clinical Evaluation, Biochemical Markers, Quality of Life, and Monitoring of Recalcification Using Assessments of Graylevel Histogram in Plain Radiographs,” International Journal of Radiation Oncology, Biol
[25] L. S. Rosen, D. Gordon, S. Tchekmedyian, R. Yanagihara, V. Hirsh, M. Krzakowski, M. Pawlicki, P. de Souza, M. Zheng, G. Urbanowitz, D. Reitsma and J. J. Seaman, “Zoledronic Acid Versus Placebo in the Treatment of Skeletal Metastases in Patients with Lung Cancer and Other Solid Tumors: A Phase III, Double-Blind, Randomized Trial. The Zoledronic Acid Lung Cancer and Other Solid Tumors Study Group,” Journal of Clinical Oncology, Vol. 21, No. 16, 2003, pp. 3150-3157. doi:10.1200/JCO.2003.04.105

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