肺癌骨轉(zhuǎn)移臨床診療專家共識

1、 顧問組成員：（按姓名漢語拼音排序）顧問組成員：（按姓名漢語拼音排序） 馮奉儀馮奉儀中國醫(yī)學科學院腫瘤醫(yī)院中國醫(yī)學科學院腫瘤醫(yī)院 郭衛(wèi)郭衛(wèi)北京大學人民醫(yī)院北京大學人民醫(yī)院 李龍蕓李龍蕓北京協(xié)和醫(yī)院北京協(xié)和醫(yī)院 廖美琳廖美琳上海市胸科醫(yī)院上海市胸科醫(yī)院 申文江申文江北京大學第一醫(yī)院腫瘤中心北京大學第一醫(yī)院腫瘤中心 沈鎮(zhèn)宙沈鎮(zhèn)宙復旦大學腫瘤醫(yī)院復旦大學腫瘤醫(yī)院 宋三泰宋三泰解放軍解放軍307307醫(yī)院醫(yī)院 吳一龍吳一龍廣東省人民醫(yī)院廣東省人民醫(yī)院 謝廣茹謝廣茹天津醫(yī)科大學腫瘤醫(yī)院天津醫(yī)科大學腫瘤醫(yī)院 余子豪余子豪中國醫(yī)學科學院腫瘤醫(yī)院中國醫(yī)學科學院腫瘤醫(yī)院 肺癌起草小組：（按姓名漢語拼音排序）肺癌

2、起草小組：（按姓名漢語拼音排序） 李進李進復旦大學醫(yī)學院腫瘤醫(yī)院復旦大學醫(yī)學院腫瘤醫(yī)院 陸舜陸舜上海市胸科醫(yī)院上海市胸科醫(yī)院 秦叔逵秦叔逵八一醫(yī)院全軍腫瘤中心八一醫(yī)院全軍腫瘤中心 王杰軍王杰軍第二軍醫(yī)大學上海長征醫(yī)院第二軍醫(yī)大學上海長征醫(yī)院 張力張力中山大學腫瘤醫(yī)院中山大學腫瘤醫(yī)院 支修益支修益首都醫(yī)科大學肺癌診療中心首都醫(yī)科大學肺癌診療中心 周彩存周彩存上海市肺科醫(yī)院腫瘤科上海市肺科醫(yī)院腫瘤科 周清華周清華四川大學華西醫(yī)院腫瘤中心四川大學華西醫(yī)院腫瘤中心 1. 1. Mundy GR. Mechanisms of bone metastasis. Cancer. 1997;80:1546-1

3、556. 2. 2. Coleman RE. Skeletal complications of malignancy. Cancer. 1997;80:1588-1594. 3. 3. Ginsberg RJ, Vokes EE, Rosenzweig K. Non-small cell lung cancer. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles 2001:925-983. 隨隨 機機 化化 分分 組組 09 個月個月 核心分析核心分析 21 個月個月 最終分析最終分析 唑來膦酸唑來膦酸 4

4、mg + 每日口服維生素每日口服維生素 D 400 IU 和鈣劑和鈣劑 500 mg 安慰劑安慰劑 +每日口服維生素每日口服維生素 D 400 IU 和鈣劑和鈣劑 500 mg n = 257 n = 250 根據(jù)非小細胞肺癌（根據(jù)非小細胞肺癌（NSCLC）和其他實體腫瘤相比進行分層）和其他實體腫瘤相比進行分層 n = 266唑來膦酸唑來膦酸 8mg +每日口服維生素每日口服維生素 D 400 IU 和鈣劑和鈣劑 500 mg 1. 1. Rosen L, Gordon D, Tchekmedyian S, et al. 擇泰significantly increased the median

5、 time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NSCLC) and other solid tumours (OST). JCO 2003;21:3150. 隨隨 機機 化化 分分 組組 09 個月個月 核心分析核心分析 21 個月個月 最終分析最終分析 唑來膦酸唑來膦酸 4 mg +每日口服維生素每日口服維生素 D 400 IU 和鈣劑和鈣劑 500 mg n = 257 安慰劑安慰劑 +每日口服維

6、生素每日口服維生素 D 400 IU 和鈣劑和鈣劑 500 mg n = 250 根據(jù)非小細胞肺癌（根據(jù)非小細胞肺癌（NSCLC）和其他實體腫瘤相比進行分層）和其他實體腫瘤相比進行分層 1. 1. Rosen L, Gordon D, Tchekmedyian S, et al. 擇泰significantly increased the median time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NS

7、CLC) and other solid tumours (OST). JCO 2003;21:3150. 1. 1. Rosen L, Gordon D, Tchekmedyian S, et al. Zometa significantly increased the median time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NSCLC) and other solid tumours (OST)

8、. Lung Cancer. 2001;34(suppl 1):67. Abstract. 1. 1. Rosen L, Gordon D, Tchekmedyian S, et al. Zometa significantly increased the median time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NSCLC) and other solid tumours (OST). Lung C

9、ancer. 2001;34(suppl 1):67. Abstract. 1. 1. Rosen L, Gordon D, Tchekmedyian S, et al. Zometa significantly increased the median time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NSCLC) and other solid tumours (OST). Lung Cancer. 2

10、001;34(suppl 1):67. Abstract. 1. 1. Rosen L, Gordon D, Tchekmedyian S, et al. Zometa significantly increased the median time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NSCLC) and other solid tumours (OST). Lung Cancer. 2001;34(s

11、uppl 1):67. Abstract. 1. 1. Rosen L, Gordon D, Tchekmedyian S, et al. 擇泰significantly increased the median time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NSCLC) and other solid tumours (OST). JCO 2003;21:3150. 1. 1. Rosen L, Go

12、rdon D, Tchekmedyian S, et al. Zometa significantly increased the median time to first skeletal related event (SRE) in patients with osteolytic bone metastases from non-small cell lung cancer (NSCLC) and other solid tumours (OST). Lung Cancer. 2001;34(suppl 1):67. Abstract. 0 0.1 0.2 0.3 0.4 0.5 0.6

13、 0.7 0.8 P P=.039=.039 ZOMETAZOMETA (zoledronic acid) 4 mg (zoledronic acid) 4 mg PlaceboPlacebo P P=.127=.127 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 ZOMETA 4 mgZOMETA 4 mg PlaceboPlacebo 27 Median, daysP value Zol 4 mg236 .009 Placebo155 唑來膦酸延遲唑來膦酸延遲SRE出現(xiàn)出現(xiàn) 2 months Days from start of treatment Percent

14、without event Zol 42571074715117 Placebo250803616116 *Hypercalcemia of malignancy is included as a skeletal-related event. 81 days IIIIII期臨床研究期臨床研究 011011 骨相關(guān)事件骨相關(guān)事件 28 Zoledronic Acid Versus Placebo Multiple Event Analysis: Other Tumour Types *Hypercalcemia of malignancy is included as a skeletal-r

15、elated event. RCC subset: Lipton A. Cancer. 2003;98:962-969. In favour of zoledronic acidIn favour of placebo P value Risk ratio (zoledronic acid 4 mg versus placebo) .003 .016 All patients NSCLC 00.20.40.60.811.21.41.61.82 Risk reduction 31% 32% 0.693 0.675 .01058%RCC 0.418 = European registration

16、= Global registration Ross JR, et al. Systemic review of role of bisphosphonates on skeletal morbidity in metas- tatic cancer. BMJ 2003; 327:46972 Ross JR, et al. Systemic review of role of bisphosphonates on skeletal morbidity in metas- tatic cancer. BMJ 2003; 327:46972 JCO 2001JCO 2001 35 Pooled P

17、rotocols 036 and 037complete response rate: normalisation of corrected serum calcium 10.8 mg/dL ( 2.7 mmol/L) Complete responders, % *Denotes statistical significance versus pamidronate. Major P, et al. J Clin Oncol. 2001;19:558-567. 0 20 40 60 80 100 Day 0Day 4Day 7Day 10 Zoledronic acid 4 mg (n =

18、86) Zoledronic acid 8 mg (n = 90) Pamidronate 90 mg (n = 99) 83.3% P = .010* 56% P = .021* 88% P = .002* 87% P = .015*82.6% P = .005* 45% 33% 64% 70% 擇泰擇泰( (唑來膦酸唑來膦酸) ) 與帕米膦酸二鈉治療與帕米膦酸二鈉治療 HCMHCM的療效比較的療效比較 36 = Censored time. Zoledronic acid 4 mg versus Pam 90 mg, P .001; Zoledronic acid 8 mg versus Pamidronate 90 mg, P = .007