[1]Huanan Wang,Feng Wang,Yonghan Wang.Effect of Amifostine on Patients with Lung Cancer Treated with Radiotherapy or Concomitant Chemoradiotherapy:A Systematic Review and Meta-Analysis of Randomized Controlled Trials[J].国际放射医学核医学杂志,2017,41(6):413-422.[doi:10.3760/cma.j.issn.1673-4114.2017.06.007]
 Huanan Wang,Feng Wang,Yonghan Wang.Effect of Amifostine on Patients with Lung Cancer Treated with Radiotherapy or Concomitant Chemoradiotherapy:A Systematic Review and Meta-Analysis of Randomized Controlled Trials[J].International Journal of Radiation Medicine and Nuclear Medicine,2017,41(6):413-422.[doi:10.3760/cma.j.issn.1673-4114.2017.06.007]
点击复制

Effect of Amifostine on Patients with Lung Cancer Treated with Radiotherapy or Concomitant Chemoradiotherapy:A Systematic Review and Meta-Analysis of Randomized Controlled Trials(/HTML)
分享到:

《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
41
期数:
2017年第6期
页码:
413-422
栏目:
论著
出版日期:
2017-12-05

文章信息/Info

Title:
Effect of Amifostine on Patients with Lung Cancer Treated with Radiotherapy or Concomitant Chemoradiotherapy:A Systematic Review and Meta-Analysis of Randomized Controlled Trials
作者:
Huanan Wang1 Feng Wang2 Yonghan Wang3
1. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin 300192, China;
2. Department of Statistics, Tianjin University of Finance and Economics, Tianjin 300204, China;
3. Department of Finance, Beijing Technology and Business University, Beijing 100048, China
Author(s):
Huanan Wang1 Feng Wang2 Yonghan Wang3
1. Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin 300192, China;
2. Department of Statistics, Tianjin University of Finance and Economics, Tianjin 300204, China;
3. Department of Finance, Beijing Technology and Business University, Beijing 100048, China
关键词:
AmifostineLung neoplasmsRadiotherapyConcomitant chemoradiotherapyMeta-analysis
Keywords:
AmifostineLung neoplasmsRadiotherapyConcomitant chemoradiotherapyMeta-analysis
DOI:
10.3760/cma.j.issn.1673-4114.2017.06.007
摘要:
Objective Amifostine is clinically used as a chemical radioprotector. Nevertheless, its efficacy as a radioprotector remains controversial. Methods PubMed, Cochrane Central Register of Controlled Trials, EMBASE, China National Knowledge Infrastructure, and the references of the published results of trials on the efficacy of amifostine in patients with lung cancer and who received radiotherapy or concomitant chemoradiotherapy were searched. The pooled radiation protection efficacy, treatment response, and side effects of amifostine were calculated using RevMan software. Results Twelve randomized controlled trials involving 1000 patients with lung cancer were ultimately analyzed. Results of meta-analysis revealed that the use of amifostine reduced the risk of acute esophageal toxicity(RR, 0.56; 95% CI, 0.39-0.81; P=0.002) and pulmonary toxicity(RR, 0.42; 95% CI, 0.25-0.70; P=0.001). Subgroup analysis also demonstrated that the risk of acute esophageal toxicity and pulmonary toxicity significantly reduced in patients who received chemoradiation concurrent with amifostine or radiation only. Pooled data showed that the use of amifostine did not significantly decrease the risk of late pulmonary toxicity(RR, 0.74; 95% CI, 0.45-1.19; P=0.210). Moreover, subgroup analysis demonstrated that the risk oflate pulmonary toxicity did not significantly decrease in patients who received chemoradiotherapy concomitant with amifostine(RR, 0.84; 95% CI, 0.48-1.46; P=0.540). Amifostine did not exert tumor-protective effects in partial response(RR,0.98; 95% CI, 0.83-1.15; P=0.800) but improved complete response(RR, 1.50; 95% CI, 1.03-2.18; P=0.030), although publication bias was observed through Egger’s test(P=0.000). Moreover, amifostine had no effect on one-year overall survival (RR, 0.94; 95% CI, 0.81-1.09; P=0.400) and two-year overall survival(RR, 1.06; 95% CI, 0.81-1.39; P=0.680) rates. The incidence of neutropenia, a hematologic side effect of amifostine, was not significantly different(RR, 1.02; 95% CI, 0.61-1.71; P=0.940) between the amifostine and control group. The use of amifostine, however, significantly decreased the incidence of thrombocytopenia(RR, 0.45; 95% CI, 0.21-0.94; P=0.030). The most common amifostine-related side effects were nausea, vomiting, and hypotension with average incidence rates of 11%, 14%, and 24%, respectively. Conclusions This systematic review showed that the concurrent administration of amifostine with radiotherapy to patients with lung cancer significantly reduced the risks of acute esophageal toxicity and acute pulmonary toxicity and decreased the incidence of thrombocytopenia without tumor-protecting effects. In addition, the toxicities of amifostine were generally controllable through clinical treatment or resting.
Abstract:
Objective Amifostine is clinically used as a chemical radioprotector. Nevertheless, its efficacy as a radioprotector remains controversial. Methods PubMed, Cochrane Central Register of Controlled Trials, EMBASE, China National Knowledge Infrastructure, and the references of the published results of trials on the efficacy of amifostine in patients with lung cancer and who received radiotherapy or concomitant chemoradiotherapy were searched. The pooled radiation protection efficacy, treatment response, and side effects of amifostine were calculated using RevMan software. Results Twelve randomized controlled trials involving 1000 patients with lung cancer were ultimately analyzed. Results of meta-analysis revealed that the use of amifostine reduced the risk of acute esophageal toxicity(RR, 0.56; 95% CI, 0.39-0.81; P=0.002) and pulmonary toxicity(RR, 0.42; 95% CI, 0.25-0.70; P=0.001). Subgroup analysis also demonstrated that the risk of acute esophageal toxicity and pulmonary toxicity significantly reduced in patients who received chemoradiation concurrent with amifostine or radiation only. Pooled data showed that the use of amifostine did not significantly decrease the risk of late pulmonary toxicity(RR, 0.74; 95% CI, 0.45-1.19; P=0.210). Moreover, subgroup analysis demonstrated that the risk oflate pulmonary toxicity did not significantly decrease in patients who received chemoradiotherapy concomitant with amifostine(RR, 0.84; 95% CI, 0.48-1.46; P=0.540). Amifostine did not exert tumor-protective effects in partial response(RR,0.98; 95% CI, 0.83-1.15; P=0.800) but improved complete response(RR, 1.50; 95% CI, 1.03-2.18; P=0.030), although publication bias was observed through Egger’s test(P=0.000). Moreover, amifostine had no effect on one-year overall survival (RR, 0.94; 95% CI, 0.81-1.09; P=0.400) and two-year overall survival(RR, 1.06; 95% CI, 0.81-1.39; P=0.680) rates. The incidence of neutropenia, a hematologic side effect of amifostine, was not significantly different(RR, 1.02; 95% CI, 0.61-1.71; P=0.940) between the amifostine and control group. The use of amifostine, however, significantly decreased the incidence of thrombocytopenia(RR, 0.45; 95% CI, 0.21-0.94; P=0.030). The most common amifostine-related side effects were nausea, vomiting, and hypotension with average incidence rates of 11%, 14%, and 24%, respectively. Conclusions This systematic review showed that the concurrent administration of amifostine with radiotherapy to patients with lung cancer significantly reduced the risks of acute esophageal toxicity and acute pulmonary toxicity and decreased the incidence of thrombocytopenia without tumor-protecting effects. In addition, the toxicities of amifostine were generally controllable through clinical treatment or resting.

参考文献/References:

[1] Senan S, Lagerwaard FJ. The role of radiotherapy in non-small-cell lung cancer[J]. Ann Oncol, 2005, 16 suppl 2:S223-228. DOI:10.1093/annonc/mdi726.
[2] Ozgen A, Hayran M, Kahraman F. Mean esophageal radiation dose is predictive of the grade of acute esophagitis in lung cancer patients treated with concurrent radiotherapy and chemotherapy[J].J Radiat Res, 2012, 53(6):916-922. DOI:10.1093/jrr/rrs056.
[3] Walker DM, Kajon AE, Torres SM, et al. WR1065 mitigates AZT-ddI-Induced mutagenesis and inhibits viral replication[J]. Environ Mol Mutagen, 2009, 50(6):460-472. DOI:10.1002/em.20482.
[4] 刘彩彩. 局部晚期非小细胞肺癌放疗中阿米福汀的作用研究[J]. 母婴世界, 2015, 15:16. Liu CC. Study on the effect of amifostine in local advanced NSCLC radiotherapy[J]. Mother Child World, 2015, 15:16.
[5] 赵衍. 阿米福汀在非小细胞肺癌放疗中对正常组织的保护研究[J]. 临床肺科杂志, 2014, 19(11):2050-2052. DOI:10.3969/j.issn.1009-6663. 2014.011.036. Zhao Y. Amifostine protective effect for normal tissue in the radiotherapy of non-small cell lung cancer[J]. J Clinic Pulmonary Med, 2014, 19(11):2050-2052.
[6] Movsas B, Scot C, Langer C, et al. Randomized trial of amifostine in locally advanced non-small-cell lung cancerpatients receiving chemotherapy and hyperfractionated radiation:radiationtherapy oncology group trial 98-01[J]. J Clin Oncol, 2005, 23(10):2145-2154. DOI:10.1200/JCO. 2005.07.167.
[7] Senzer N. A phase Ⅲ randomized evaluation of amifostine in stage ⅢA/ⅢB non-small celllung cancer patients receiving concurrent carboplatin, paclitaxel, and radiation therapy followed by gemcitabine and cisplatin intensification:preliminary findings[J].Semin Oncol, 2002, 29(6 suppl 19):S38-41. DOI:10.1053/sonc.2002.37361.
[8] Koukourakis MI. Amifostine:is there evidence of tumor protection?[J]. Semin Oncol, 2003, 30(6 Suppl 18):S18-30. DOI:10.1053/j.seminoncol.2003.11.014.
[9] Shuster JJ. Review:Cochrane handbook forsystematic reviews for interventions, Version 5.1.0, published 3/2011. Julian P.T. Higgins and Sally Green, Editors[J]. Res Syn Meth, 2011, 2(2):126-130. DOI:10.1002/jrsm.38.
[10] DerSimonian R, Laird N. Meta-analysis in clinical trials[J]. Control Clin Trials,1986, 7(3):177-188.
[11] Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses[J]. BMJ, 2003, 327(7414):557-560. DOI:10.1136/bmj.327.7414.557.
[12] Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test[J]. BMJ, 1997, 315(7109):629-634. DOI:10.1136/bmj.315.7109.629.
[13] 林展, 严浩林, 朱海生, 等. 阿米福汀在局部晚期非小细胞肺癌放疗中的作用研究[J]. 中国全科医学, 2013, 16(4):1247-1249. DOI:10.3969/j.issn.1007-9572. 2013.04.053. Lin Z, Yan HL, Zhu HS, et al. Short-term effects of amifostine on locally advanced NSCLC patients treated with radiotherapy[J]. Chin Gen Pract, 2013, 16(4):1247-1249.
[14] 李永强, 周翔, 张霆. 阿米福汀对肺癌放疗中不良反应的影响[J].现代肿瘤医学, 2010, 18(4):708-711. DOI:10.3969/j.issn.1672-4992.2010.04.27. Li YQ, Zhou X, Zhang T. The effect of amifostine on toxicity of radiotherapy in lung cancer treatment[J]. Mod Oncol, 2010, 18(4):708-711.
[15] 翁向群, 庄聪文, 程先进, 等. 氨磷汀配合紫杉醇和顺铂同步放化疗治疗局部晚期非小细胞肺癌的临床分析[J]. 临床军医杂志, 2007, 35(6):817-819. DOI:10.3969/j.issn.1671-3826. 2007. 06. 004. Weng XQ, Zhuang CW, Cheng XJ, et al. Clinical study on efficacy of compound amifostine with radiochemotherapy in treatment of local advanced NSCLC[J]. Clin J Med Office, 2007, 35(6):817-819.
[16] Komaki R, Lee JS, Milas L, et al. Effects of amifostine on acute toxicity from concurrent chemotherapy and radiotherapy for inoperable non-small-cell lung cancer:report of a randomized comparative trial[J]. Int J Radiat Oncol Biol Phys, 2004, 58(5):1369-1377. DOI:10.1016/j.ijrobp.2003.10.005.
[17] Leong SS, Tan EH, Fong KW, et al. Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage Ⅲ non-small-cell lung cancer[J]. J Clin Oncol,2003, 21(9):1767-1774. DOI:10.1200/JCO.2003.11.005.
[18] Antonadou D, Throuvalas N, Petridis A, et al. Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small-cell lung cancer[J]. Int J Radiat Oncol Biol Phys, 2003, 57(2):402-408. DOI:10.1016/S0360-3016(03)00590-X.
[19] Antonadou D, Coliarakis N, Synodinou M, et al. Randomized phase Ⅲ trial of radiation treatment ±amifostine in patients with advanced-stage lung cancer[J]. Int J Radiat Oncol Biol Phys, 2001, 51(4):915-922. DOI:10.1016/S0360-3016(01)01713-8.
[20] Koukourakis MI, Kyrias G, Kakolyris S, et al. Subcutaneous administration of amifostine during fractionated radiotherapy:a randomized phase Ⅱ study[J]. J Clin Oncol, 2000, 18(11):2226-2233. DOI:10.1200/JCO.2000.18.11.2226.
[21] Ricciuti B, Brambilla M, Metro G, et al. Targeting NTRK fusion in non-small cell lung cancer:rationale and clinical evidence[J]. Med Oncol, 2017, 34(6):105. DOI:10.1007/s12032-017-0967-5.
[22] Antonadou D. Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung cancer[J]. Semin Radiat Oncol, 2002, 12(1 suppl 1):S50-58. DOI:10.1053/srao.2002.31374.
[23] Koukourakis MI. Amifostine in clinical oncology:current use and future applications[J]. Anticancer Drugs, 2002, 13(3):181-209. DOI:10.1097/00001813-200203000-00001.

相似文献/References:

[1]顾宏涛.细胞防护剂WR-2721研究进展[J].国际放射医学核医学杂志,2003,27(3):135.
 GU Hong-tao.Advances in research of the cytoprotector WR-2721[J].International Journal of Radiation Medicine and Nuclear Medicine,2003,27(6):135.

备注/Memo

备注/Memo:
收稿日期:2017-10-12。
基金项目:Medical and Health Science and Technology Innovation Project of Chinese Academy of Medical Sciences(2017-I2M-3-019)
通讯作者:Yonghan Wang,Email:18963974852@163.com
更新日期/Last Update: 2017-12-05