Zoledronic Acid Combined Radiotherapy for Bone Metastasis of Non-small Cell Lung Cancer

Summary

This study will give comparison of the bone pain remission and the adverse reaction of Zoledronic acid combine with High dose fractionation radiotherapy(30Gy/10f) and Zoledronic acid combine with low dose fractionation radiotherapy(15Gy/5f) . The purpose of this trial is to prove whether Zoledronic acid combine radiotherapy can reduce radiotherapy dose in treatment of non-small cell lung cancer bone metastasis'pain relief or not.

Timeline

Start

2019-06

Primary completion

2021-09

Completion

2022-12

Publications

• Background Akbar RA, Gosh SK, Khalil S, ul Haq SM. Zoledronic acid in metastatic bone disease: an audit based discussion. J Ayub Med Coll Abbottabad. 2010 Jul-Sep;22(3):5-7.
• Background Wu JS, Wong R, Johnston M, Bezjak A, Whelan T; Cancer Care Ontario Practice Guidelines Initiative Supportive Care Group. Meta-analysis of dose-fractionation radiotherapy trials for the palliation of painful bone metastases. Int J Radiat Oncol Biol Phys. 2003 Mar 1;55(3):594-605. doi: 10.1016/s0360-3016(02)04147-0.
• Background Chow E, Wu JS, Hoskin P, Coia LR, Bentzen SM, Blitzer PH. International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Radiother Oncol. 2002 Sep;64(3):275-80. doi: 10.1016/s0167-8140(02)00170-6.
• Background Chow E, Hoskin P, Mitera G, Zeng L, Lutz S, Roos D, Hahn C, van der Linden Y, Hartsell W, Kumar E; International Bone Metastases Consensus Working Party. Update of the international consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases. Int J Radiat Oncol Biol Phys. 2012 Apr 1;82(5):1730-7. doi: 10.1016/j.ijrobp.2011.02.008. Epub 2011 Apr 12.
• Background Dennis K, Makhani L, Zeng L, Lam H, Chow E. Single fraction conventional external beam radiation therapy for bone metastases: a systematic review of randomised controlled trials. Radiother Oncol. 2013 Jan;106(1):5-14. doi: 10.1016/j.radonc.2012.12.009. Epub 2013 Jan 13.
• Background Luo KW, Ko CH, Yue GG, Lee MY, Siu WS, Lee JK, Shum WT, Fung KP, Leung PC, Li G, Evdokiou A, Lau CB. Anti-tumor and anti-osteolysis effects of the metronomic use of zoledronic acid in primary and metastatic breast cancer mouse models. Cancer Lett. 2013 Oct 1;339(1):42-8. doi: 10.1016/j.canlet.2013.07.024. Epub 2013 Jul 26.
• Background Denham JW, Wilcox C, Joseph D, Spry NA, Lamb DS, Tai KH, Matthews J, Atkinson C, Turner S, Christie D, Gogna NK, Kenny L, Duchesne G, Delahunt B, McElduff P. Quality of life in men with locally advanced prostate cancer treated with leuprorelin and radiotherapy with or without zoledronic acid (TROG 03.04 RADAR): secondary endpoints from a randomised phase 3 factorial trial. Lancet Oncol. 2012 Dec;13(12):1260-70. doi: 10.1016/S1470-2045(12)70423-0. Epub 2012 Nov 12.
• Background Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial. Lancet Oncol. 2014 Sep;15(10):1076-89. doi: 10.1016/S1470-2045(14)70328-6. Epub 2014 Aug 14.
• Background Deberne M, Ropert S, Billemont B, Daniel C, Chapron J, Goldwasser F. Inaugural bone metastases in non-small cell lung cancer: a specific prognostic entity? BMC Cancer. 2014 Jun 10;14:416. doi: 10.1186/1471-2407-14-416.
• Background Peng H, Ma M, Han B. [Survival analysis of 1,742 patients with stage IV non-small cell lung cancer]. Zhongguo Fei Ai Za Zhi. 2011 Apr;14(4):362-6. doi: 10.3779/j.issn.1009-3419.2011.04.11. Chinese.
• Background Bae HM, Lee SH, Kim TM, Kim DW, Yang SC, Wu HG, Kim YW, Heo DS. Prognostic factors for non-small cell lung cancer with bone metastasis at the time of diagnosis. Lung Cancer. 2012 Sep;77(3):572-7. doi: 10.1016/j.lungcan.2012.05.094. Epub 2012 Jun 4.
• Background Nakamura N, Shikama N, Wada H, Harada H, Nozaki M, Nagakura H, Tago M, Oguchi M, Uchida N; Japanese Radiation Oncology Study Group Working Subgroup of Palliative Radiotherapy. Patterns of practice in palliative radiotherapy for painful bone metastases: a survey in Japan. Int J Radiat Oncol Biol Phys. 2012 May 1;83(1):e117-20. doi: 10.1016/j.ijrobp.2011.11.075. Epub 2012 Feb 28.
• Background Brown JE, Cook RJ, Major P, Lipton A, Saad F, Smith M, Lee KA, Zheng M, Hei YJ, Coleman RE. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors. J Natl Cancer Inst. 2005 Jan 5;97(1):59-69. doi: 10.1093/jnci/dji002.
• Background Sun JM, Ahn JS, Lee S, Kim JA, Lee J, Park YH, Park HC, Ahn MJ, Ahn YC, Park K. Predictors of skeletal-related events in non-small cell lung cancer patients with bone metastases. Lung Cancer. 2011 Jan;71(1):89-93. doi: 10.1016/j.lungcan.2010.04.003. Epub 2010 Jul 3.
• Background Zhang L, Hou X, Lu S, Rao H, Hou J, Luo R, Huang H, Zhao H, Jian H, Chen Z, Liao M, Wang X. Predictive significance of bone sialoprotein and osteopontin for bone metastases in resected Chinese non-small-cell lung cancer patients: a large cohort retrospective study. Lung Cancer. 2010 Jan;67(1):114-9. doi: 10.1016/j.lungcan.2009.03.017.
• Background Dennis K, Wong K, Zhang L, Culleton S, Nguyen J, Holden L, Jon F, Tsao M, Danjoux C, Barnes E, Sahgal A, Zeng L, Koo K, Chow E. Palliative radiotherapy for bone metastases in the last 3 months of life: worthwhile or futile? Clin Oncol (R Coll Radiol). 2011 Dec;23(10):709-15. doi: 10.1016/j.clon.2011.05.004. Epub 2011 Jun 12.
• Background Hirsh V. Skeletal disease contributes substantially to morbidity and mortality in patients with lung cancer. Clin Lung Cancer. 2009 Jul;10(4):223-9. doi: 10.3816/CLC.2009.n.030.
• Background Pandya KJ, Gajra A, Warsi GM, Argonza-Aviles E, Ericson SG, Wozniak AJ. Multicenter, randomized, phase 2 study of zoledronic acid in combination with docetaxel and carboplatin in patients with unresectable stage IIIB or stage IV non-small cell lung cancer. Lung Cancer. 2010 Mar;67(3):330-8. doi: 10.1016/j.lungcan.2009.04.020. Epub 2009 Jun 2.
• Background Cheon PM, Pulenzas N, Zhang L, Mauti E, Wong E, Thavarajah N, Tsao M, Danjoux C, Holden L, DeAngelis C, Chow E. Fatigue scores in patients receiving palliative radiotherapy for painful bone metastases. Support Care Cancer. 2015 Jul;23(7):2097-103. doi: 10.1007/s00520-014-2561-0. Epub 2014 Dec 24.
• Background Cole DJ. A randomized trial of a single treatment versus conventional fractionation in the palliative radiotherapy of painful bone metastases. Clin Oncol (R Coll Radiol). 1989 Nov;1(2):59-62. doi: 10.1016/s0936-6555(89)80035-4.
• Background Wu JS, Bezjak A, Chow E, Kirkbride P. Primary treatment endpoint following palliative radiotherapy for painful bone metastases: need for a consensus definition? Clin Oncol (R Coll Radiol). 2002 Feb;14(1):70-7. doi: 10.1053/clon.2001.0012.
• Background Popovic M, den Hartogh M, Zhang L, Poon M, Lam H, Bedard G, Pulenzas N, Lechner B, Chow E. Review of international patterns of practice for the treatment of painful bone metastases with palliative radiotherapy from 1993 to 2013. Radiother Oncol. 2014 Apr;111(1):11-7. doi: 10.1016/j.radonc.2014.01.015. Epub 2014 Feb 20.
• Background Westhoff PG, de Graeff A, Reyners AK, Monninkhof EM, Rodenhuis CC, van Vulpen M, Leer JW, Marijnen CA, van der Linden YM; Dutch Bone Metastasis Study Group. Effect of age on response to palliative radiotherapy and quality of life in patients with painful bone metastases. Radiother Oncol. 2014 May;111(2):264-9. doi: 10.1016/j.radonc.2014.03.017. Epub 2014 Apr 17.
• Background Konski A, James J, Hartsell W, Leibenhaut MH, Janjan N, Curran W, Roach M, Watkins-Bruner D. Economic analysis of radiation therapy oncology group 97-14: multiple versus single fraction radiation treatment of patients with bone metastases. Am J Clin Oncol. 2009 Aug;32(4):423-8. doi: 10.1097/COC.0b013e31818da9f7.
• Background Li YY, Chang JW, Chou WC, Liaw CC, Wang HM, Huang JS, Wang CH, Yeh KY. Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers. Lung Cancer. 2008 Feb;59(2):180-91. doi: 10.1016/j.lungcan.2007.08.026. Epub 2007 Sep 27.
• Background Lipton A. Treatment of bone metastases and bone pain with bisphosphonates. Support Cancer Ther. 2007 Jan 1;4(2):92-100. doi: 10.3816/SCT.2007.n.003.
• Background Henk H, Teitelbaum A, Kaura S. Evaluation of the clinical benefit of long-term (beyond 2 years) treatment of skeletal-related events in advanced cancers with zoledronic acid. Curr Med Res Opin. 2012 Jul;28(7):1119-27. doi: 10.1185/03007995.2012.689254. Epub 2012 May 17.
• Background Wang Z, Qiao D, Lu Y, Curtis D, Wen X, Yao Y, Zhao H. Systematic literature review and network meta-analysis comparing bone-targeted agents for the prevention of skeletal-related events in cancer patients with bone metastasis. Oncologist. 2015 Apr;20(4):440-9. doi: 10.1634/theoncologist.2014-0328. Epub 2015 Mar 2.
• Background 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 Sep;5(6):390-6. doi: 10.3816/CGC.2007.n.022.
• Results Takeda N, Isu K, Hiraga H, Shinohara N, Minami A, Kamata H. Zoledronic acid enhances the effect of radiotherapy for bone metastases from renal cell carcinomas: more than a 24-month median follow-up. J Orthop Sci. 2012 Nov;17(6):770-4. doi: 10.1007/s00776-012-0294-9. Epub 2012 Oct 2.
• Results Atahan L, Yildiz F, Cengiz M, Kaplan B, Ozkan M, Yazici G, Gundog M, Haydaroglu A, Korcum AF, Sengoz M, Dincer M, Akmansu M, Engin K, Hayran M. Zoledronic acid concurrent with either high- or reduced-dose palliative radiotherapy in the management of the breast cancer patients with bone metastases: a phase IV randomized clinical study. Support Care Cancer. 2010 Jun;18(6):691-8. doi: 10.1007/s00520-009-0663-x. Epub 2009 May 31.

Drugs

Indications