帕米膦酸二鈉和唑來膦酸治療非小細胞肺癌骨轉移療效和安全性比較_《華西醫學》

作者：

鄒炳文 , 宋海俠 , 張瑜 , 周麟 , 朱江 , 劉詠梅 , 黃媚娟 , 李潞 ,  徐泳

四川大學華西醫院腫瘤中心胸部腫瘤科（成都，610041）;

關鍵詞：

非小細胞肺癌骨轉移骨相關事件帕米膦酸二鈉唑來膦酸

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【摘要】　目的　評價伴骨轉移的非小細胞肺癌（non-small cell lung cancer，NSCLC）患者在接受帕米膦酸二鈉和唑來膦酸治療后的有效性和安全性。　方法　 2007年6月-2008年12月，74例伴骨轉移的NSCLC，患者接受了雙膦酸鹽治療，其中50例接受帕米膦酸二鈉治療，24例接受唑來膦酸治療。帕米膦酸二鈉90 mg，靜脈滴注3 h，每4周重復1次；唑來膦酸4 mg，靜脈滴注15 min，每4周重復1次。對可能影響其骨相關事件發生時間及生存率的各種臨床﹑病理、治療方法等因素進行分析，用Kaplan-Meier曲線及Log rank檢驗生存率差異，對不良反應的發生率等采用χ2檢驗。　結果　 18個月無骨相關事件生存率和總體生存率在帕米膦酸二鈉及唑來膦酸組分別為19.3%、28.9%（P=0.253）和33.4%、38.2%（P=0.745），兩組比較，差異均無統計學意義。兩組患者不良反應中帕米膦酸二鈉組8例（16.0%），唑來膦酸組6例（25.0%），兩組比較差異無統計學意義（χ2=0.200，P=0.655）。7例患者用帕米膦酸二鈉治療失敗后再用唑來膦酸治療，其中位無骨相關事件生存時間為2個月（95%CI：0~4.6）。　結論　唑來膦酸和帕米膦酸二鈉在緩解延遲骨相關事件發生時間療效和不良反應發生率相當。用帕米膦酸二鈉治療失敗后再用唑來膦酸可延緩骨相關事件發生時間。
【Abstract】　Objective　 To retrospectively evaluate the efficacy and safety of pamidronate disoclium and zoledronic acid in treating non-small-cell lung cancer (NSCLC) patients with bone metastasis.　Methods　 This study included 74 patients who were treated with bisphosphonate between June 2007 and December 2008. Fifty were treated with pamidronate disodium, and 24 with zoledronic acid. Pamidronate disodium was administered intravenously once for 3 hours every 4 weeks at a dose of 90 mg. Zoledronic acid was given intravenously once for 15 minutes every 4 weeks at a dose of 4 mg. Various clinical, pathological factors and treatment methods related to the occurring time of skeletal related events (SRE) and survival rate were analyzed. Kaplan-Meier curve and Log rank were adopted to detect the difference in survival rate between patients treated with different medicine, and we used χ2 test to discover the rate of adverse events of the patients.　Results　 Eighteen-month SRE-free survival and overall survival rate in the pamidronate disodium and zoledronic acid group were 19.3% vs. 28.9% (P=0.253), and 33.4% vs. 38.2% (P=0.745) respectively. There were 8 (8/50) cases of adverse events in the pamidronate disodium group, and 6 (6/24) in the zoledronic acid group (χ2=0.200, P=0.655). The SRE-free survival time for seven patients who were treated with zoledronic acid after pamidronate disodium failed was 2 months (95%CI: 0-4.6).　Conclusions　 Compared with zoledronic acid, pamidronate has equal efficacy in delaying SRE and incidence of adverse effects. Administering zoledronic acid after pamidronate failed can also delay the occurring time of SRE.

引用本文： 鄒炳文,宋海俠,張瑜,周麟,朱江,劉詠梅,黃媚娟,李潞,徐泳. 帕米膦酸二鈉和唑來膦酸治療非小細胞肺癌骨轉移療效和安全性比較. 華西醫學, 2011, 26(2): 212-215. doi: 復制

1.	Coleman RE. Skeletal complications of malignancy[J]. Cancer, 1997, 80(Suppl 8): 1588-1594.
2.	Coleman RE. Bisphosphonates: clinical experience[J]. Oncologist, 2004, 9(Suppl 4): 14-27.
3.	Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies[J]. Cancer Treat Rev, 2001, 27(3): 165-176.
4.	Weinfurt KP, Li Y, Castel LD, et al. The impact of skeletal of life of patients with metastatic prostate cancer[J]. Ann Oncol, 2002, 13(Suppl 5): 180.
5.	Major PP, Cook R. Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints[J]. Am J Clin Oncol, 2002, 25(Suppl 1): 10-18.
6.	Tyrrell CJ. Role of pamidronate in the management of bone metases from breast cancer[J]. Ann Oncol, 1994, 5(Suppl 7): 37.
7.	Coxon FP, Rogers MJ. The role of prenylated small GTP binding proteins in regulation of osteoclast function[J]. Calcif Tissue Int, 2003, 72(1): 80-84.
8.	Benford HL, McGowan NW, Helfich MH, et al. Visualization of bisphosphonate-induced caspase-3 active in apoptotic osteoclasts in vitro[J]. Bone, 2001, 28(5): 465-473.
9.	Monkkonen H, Lehenkari PP, Kellinsalmi M, et al. A new mechanism of action for bisphosphonates appidedicated cytotoxicty of N-BPs[J]. Bone, 2004, 34(Suppl 1): S66-S67.
10.	Rogers MJ. New insights in to the molecular mechanism of action of bisphospbonates[J]. Curr Pharm Des, 2003, 9(32): 2643-2658.
11.	van Beek ER, Cohen LH, Leroy JM, et al. Different the mechanism of an tiresorptive action of nitrogen containing bisphosphonate[J]. Bone, 2003, 33(5): 805-811.
12.	Coleman RE, Major P, Lipton A, et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid[J]. JCO, 2005, 23(22): 4925-4935.
13.	鄧坤, 王愛秋. 唑來膦酸聯合化療治療肺癌骨轉移的療效觀察[J]. 中國老年保健醫學, 2009, 7(3): 33-34.
14.	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[J]. Cancer, 2004, 100(1): 36-43.
15.	張力, 管忠震, 何友兼. 帕米膦酸二鈉與氯甲膦酸二鈉治療晚期腫瘤骨轉移的隨機對照臨床研究[J]. 癌癥, 1997, 16(6): 430.
16.	Wong R, Wiffen PJ. Bisphosphonates for the relief of pain secondary to bone metastases[J]. Cochrane Database Syst Rev, 2002, (2): CD002068.
17.	李會齊, 李瑤. 帕米膦酸二鈉治療惡性腫瘤骨轉移性骨痛療效分析[J]. 臨床和實驗醫學雜志, 2005, 4(4): 212-214.

1. 　Coleman RE. Skeletal complications of malignancy[J]. Cancer, 1997, 80(Suppl 8): 1588-1594.
2. 　Coleman RE. Bisphosphonates: clinical experience[J]. Oncologist, 2004, 9(Suppl 4): 14-27.
3. 　Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies[J]. Cancer Treat Rev, 2001, 27(3): 165-176.
4. 　Weinfurt KP, Li Y, Castel LD, et al. The impact of skeletal of life of patients with metastatic prostate cancer[J]. Ann Oncol, 2002, 13(Suppl 5): 180.
5. 　Major PP, Cook R. Efficacy of bisphosphonates in the management of skeletal complications of bone metastases and selection of clinical endpoints[J]. Am J Clin Oncol, 2002, 25(Suppl 1): 10-18.
6. 　Tyrrell CJ. Role of pamidronate in the management of bone metases from breast cancer[J]. Ann Oncol, 1994, 5(Suppl 7): 37.
7. 　Coxon FP, Rogers MJ. The role of prenylated small GTP binding proteins in regulation of osteoclast function[J]. Calcif Tissue Int, 2003, 72(1): 80-84.
8. 　Benford HL, McGowan NW, Helfich MH, et al. Visualization of bisphosphonate-induced caspase-3 active in apoptotic osteoclasts in vitro[J]. Bone, 2001, 28(5): 465-473.
9. 　Monkkonen H, Lehenkari PP, Kellinsalmi M, et al. A new mechanism of action for bisphosphonates appidedicated cytotoxicty of N-BPs[J]. Bone, 2004, 34(Suppl 1): S66-S67.
10. 　Rogers MJ. New insights in to the molecular mechanism of action of bisphospbonates[J]. Curr Pharm Des, 2003, 9(32): 2643-2658.
11. 　van Beek ER, Cohen LH, Leroy JM, et al. Different the mechanism of an tiresorptive action of nitrogen containing bisphosphonate[J]. Bone, 2003, 33(5): 805-811.
12. 　Coleman RE, Major P, Lipton A, et al. Predictive value of bone resorption and formation markers in cancer patients with bone metastases receiving the bisphosphonate zoledronic acid[J]. JCO, 2005, 23(22): 4925-4935.
13. 　鄧坤, 王愛秋. 唑來膦酸聯合化療治療肺癌骨轉移的療效觀察[J]. 中國老年保健醫學, 2009, 7(3): 33-34.
14. 　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[J]. Cancer, 2004, 100(1): 36-43.
15. 　張力, 管忠震, 何友兼. 帕米膦酸二鈉與氯甲膦酸二鈉治療晚期腫瘤骨轉移的隨機對照臨床研究[J]. 癌癥, 1997, 16(6): 430.
16. 　Wong R, Wiffen PJ. Bisphosphonates for the relief of pain secondary to bone metastases[J]. Cochrane Database Syst Rev, 2002, (2): CD002068.
17. 　李會齊, 李瑤. 帕米膦酸二鈉治療惡性腫瘤骨轉移性骨痛療效分析[J]. 臨床和實驗醫學雜志, 2005, 4(4): 212-214.

《華西醫學》

帕米膦酸二鈉和唑來膦酸治療非小細胞肺癌骨轉移療效和安全性比較

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《華西醫學》

帕米膦酸二鈉和唑來膦酸治療非小細胞肺癌骨轉移療效和安全性比較

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