Int J Stomatol

Int J Stomatol ›› 2020, Vol. 47 ›› Issue (5): 547-556.doi: 10.7518/gjkq.2020084

• Original Articles • Previous Articles     Next Articles

Meta-analysis and GRADE evaluation of the intervention effects of using amifostine before radiotherapy on xerostomia in patients with head and neck cancer

Wei Binbin1(),Hu Huiwei1,Liu Yujuan1,Sun Zhe2,Yi Yuli1()   

  1. 1.Nursing School of Nanchang University, Nanchang 330006, China
    2.Dept. of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang 330006, China
  • Received:2019-12-03 Revised:2020-06-05 Online:2020-09-01 Published:2020-09-16
  • Contact: Yuli Yi E-mail:1600561457@qq.com;Sunyi2628@163.com
  • Supported by:
    Key Research and Development Project of Jiangxi Province(20161BBG70069)

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Abstract:

Objective To evaluate the intervention effect of using amifostine before radiotherapy on xerostomia and other side effects in patients with head and neck cancer. Methods First, related studies were collected from different databases, such as China National Knowledge Infrastructure (CNKI), WanFang Data Knowledge Service Platform, China Biology Medicine disc (CBMdisc), VIP Database for Chinese Technical Periodicals (VIP), PubMed, Cochrane Library, EMbase, and Medline, from the date of their establishment to July 2019. Second, the collected studies were screened and evaluated based on inclusion and exclusion criteria. Third, meta-analysis was performed using RevMan5.3 software. Lastly, the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) evidence quality grading system was used to evaluate the evidence quality of the outcome indexes. Results A total of 948 patients were enrolled in nine randomized control trials (RCTs). The results of the meta-analysis showed that compared with the control group, amifostine reduced acute xerostomia above grade 2 [risk ratio (RR)=0.62, 95% CI (0.44, 0.87), P=0.005], six months after the end of radiotherapy [RR=0.58, 95% CI (0.37, 0.91), P=0.02]. No significant difference was observed in the glandular function index after the radiotherapy, advanced xerostomia 12 months after radiotherapy, acute mucositis, disease control, and overall survival (P>0.05). Amifostine caused various side effects, including nausea and vomiting, hypotension, and allergic reactions, and the difference was statistically significant (P<0.05). The results of the GRADE evidence quality evaluation indicated that 1) the five outcome indexes of acute xerostomia above grade 2, nausea and vomiting, allergic reaction, disease control, and overall survival were moderate-level evidences; 2) the outcome indexes of advanced xerostomia above grade 2, acute mucositis, and hypotension were low-level evidences; and 3) the glandular function index was an extremely low-level evidence. Conclusion Using amifostine before radiotherapy can reduce moderate to severe acute xerostomia within six months after the completion of radiotherapy, as well as the occurrence of acute mucositis. However, no positive effect was observed in the glands function after radiotherapy, xerostomia 12 months after the completion of radiotherapy, acute mucositis, and tumor therapeutic effect. Moreover, the side effects of using amifostine were remarkable. Comprehensive research with large samples should be conducted to verify this conclusion.

Key words: amifostine, head and neck neoplasms, radiotherapy

CLC Number: 

  • R739.8

TrendMD: 

Fig 1

Literature screening procedure"

Tab 1

General characteristics of included studies"

参考
文献		 国家/
地区		 例数
（T/C）		 年龄/岁 肿瘤原发部位 疾病
分期		 治疗方法 实验组T 对照组C 结局指标
[8] 希腊 22/23 53.3±6.9 鼻咽、口腔、喉、 T2N0M0 常规放射治疗+同 氨磷汀 空白 ②a④a⑤e⑥e
口咽 期化学治疗
[9] 中国 14/17 51.46±11.7 鼻咽 Ⅱ~Ⅳ 常规放射治疗 氨磷汀 安慰剂 ①e④e⑤e
[10] 荷兰 30/31 22~73 口腔、口咽、喉等 Ⅲ/ⅣB 三维放射治疗 氨磷汀 空白 ②a⑤c⑥c⑦c⑧⑨
[11] 美国、欧洲 67/65 23~78 口咽、口腔、鼻咽、 T1~TX, 常规放射治疗+同 氨磷汀 安慰剂 ①a②a④a⑤b⑦b
下咽等 N0~N3 期化学治疗 ⑧⑨
[12] 中国 108/108 未述 鼻咽、口腔、口咽、 Ⅰ~Ⅳ 三维适形放射治疗 氨磷汀 空白 ①a④a
下咽、喉等
[13] 美国、德国、 150/153 28~78 鼻咽、口腔、口咽、 T0~TX, 根治性放射治疗或 氨磷汀 空白 ①a②a④a⑤b⑥b
法国 下咽、喉等 N0~NX 术后放射治疗 ⑦b⑧⑨
[14] 澳大利亚 20/21 37~81 口腔、口咽、下咽、 T1~TX, 术后放射治疗或同 氨磷汀 安慰剂 ①a②a④a⑤b⑥
鼻咽、喉等 N0~N2 期放射、化学治疗 b⑨
或单纯放射治疗
[15] 中国 40/40 51.9±6.42 鼻咽 Ⅱ~Ⅳ 调强放射治疗 氨磷汀 安慰剂 ①e③d
[16] 中国 19/20 19~61 甲状腺 未述 术后131I放射治疗 氨磷汀 维生素C ①e③d

Tab 2

Methodological quality evaluation of included studies"

参考
文献		 随机序列的产生 分配隐藏 对研究对象、干
预者实施盲法		 对结果测评
者实施盲法		 失访偏倚风险 选择性报告结
果偏倚风险		 其他偏
倚风险
[8] 不清楚 未述 未述 未述 有失访,做了意向性分析 低 低
[9] 按随机数字表法分组 未述 未述 未述 无失访 低 低
[10] 计算机置换块随机分组 是 未述 未述 有失访,做了意向性分析 不清楚 低
[11] 按分层随机方法分组 是 是 未述 有失访,做了意向性分析 不清楚 低
[12] 不清楚 未述 未述 未述 无失访 低 低
[13] 不清楚 开放标签 开放标签 开放标签 有失访,做了意向性分析 低 低
[14] 按计算机生成的随机图表分配 是 是 是 有失访,做了意向性分析 不清楚 低
[15] 不清楚 未述 未述 未述 无失访 低 低
[16] 不清楚 未述 未述 未述 无失访 低 低

Fig 2

Meta-analysis of acute xerostomia above grade 2 in amifostine group and control group"

Fig 3

Meta-analysis of advanced xerostomia above grade 2 in amifostine group and control group"

Fig 4

Meta-analysis of parotid gland function index after radiotherapy in amifostine group and control group"

Fig 5

Meta-analysis of salivary gland function index after radiotherapy in amifostine group and control group"

Fig 6

Meta-analysis of acute mucositis after radiotherapy in amifostine group and control group"

Tab 3

Meta analysis of secondary outcomes"

结局指标 分组 纳入研究数 异质性检验结果 效应模型 Meta分析结果
I2/% P值 OR（95% CI） P值
恶心、呕吐 总体 5[8-10,13-14] 36 0.18 固定 3.73（2.43,5.71） <0.000 01
3级以上 5[9-11,13-14] 0 0.64 固定 3.06（1.44,6.53） 0.004
低血压 总体 4[8,10,13-14] 0 0.62 固定 8.37（2.90,24.18） <0.000 1
3级以上 3[10,13-14] - - 固定 2.07（0.37,11.47） 0.41
过敏反应 总体 2[10,13] 0 0.57 固定 12.02（1.53,94.77） 0.02
3级以上 3[10-11,13] 0 0.77 固定 7.20（0.88,58.94） 0.07
局部区域控制 1年 2[11,13] 30 0.23 固定 0.87（0.58,1.32） 0.52
2年 2[10,13] 0 0.65 固定 0.90（0.59,1.38） 0.62
总体生存 1年 2[11,13] 33 0.22 固定 1.30（0.79,2.14） 0.31
2年 2[10,13] 28 0.24 固定 1.10（0.71,1.71） 0.68

Tab 4

Outcomes of GRADE evidence evaluation"

结局指标及研究 证据质量评价 质量分级 结局重要性
偏倚风险 不一致性 间接性 不精确性 发表偏倚 升级条件
2级以上急性口干[9,11-16] 严重1 不严重 不严重 不严重 未察觉 无 中 关键
2级以上晚期口干[8,10-11,13-14] 严重1 不严重 不严重 严重2 未察觉 无 低 关键
腺体功能[15,16] 严重1 严重3 不严重 严重4 未察觉 无 极低 关键
急性黏膜炎[8-9,11-14] 严重1 严重3 不严重 不严重 未察觉 无 低 重要
恶心、呕吐[8-11,13-14] 严重1 不严重 不严重 不严重 未察觉 无 中 次要
低血压[8,10,13-14] 严重1 不严重 不严重 严重4 未察觉 无 低 次要
过敏反应[10-11,13] 严重1 不严重 不严重 不严重 未察觉 无 中 次要
局部区域控制[10-11,13] 严重1 不严重 不严重 不严重 未察觉 无 中 次要
总体生存情况[10-11,13] 严重1 不严重 不严重 不严重 未察觉 无 中 次要
[1] Siddiqui F, Movsas B. Management of radiation to-xicity in head and neck cancers[J]. Semin Radiat Oncol, 2017,27(4):340-349.
doi: 10.1016/j.semradonc.2017.04.008 pmid: 28865517
[2] Riley P, Glenny AM, Hua F, et al. Pharmacological interventions for preventing dry mouth and salivary gland dysfunction following radiotherapy[J]. Cochrane Database Syst Rev, 2017, 7: CD012744.
doi: 10.1002/14651858.CD013684 pmid: 32691879
[3] Strojan P, Hutcheson KA, Eisbruch A, et al. Treat-ment of late sequelae after radiotherapy for head and neck cancer[J]. Cancer Treat Rev, 2017,59:79-92.
pmid: 28759822
[4] Vissink A, van Luijk P, Langendijk JA, et al. Current ideas to reduce or salvage radiation damage to sa-livary glands[J]. Oral Dis, 2015,21(1):e1-e10.
doi: 10.1111/odi.12222 pmid: 24581290
[5] de Castro G Jr, Federico MH. Evaluation, prevention and management of radiotherapy-induced xerostomia in head and neck cancer patients[J]. Curr Opin Oncol, 2006,18(3):266-270.
doi: 10.1097/01.cco.0000219256.37843.83 pmid: 16552239
[6] Jensen SB, Pedersen AM, Vissink A, et al. A syste-matic review of salivary gland hypofunction and xerostomia induced by cancer therapies: manage-ment strategies and economic impact[J]. Support Care Cancer, 2010,18(8):1061-1079.
doi: 10.1007/s00520-010-0837-6
[7] 龙小庆, 王继生, 贾霖, 等. 三乙醇胺防治放射性皮炎有效性的Meta分析及GRADE证据质量评价[J]. 中国药房, 2019,30(2):258-263.
Long XQ, Wang JS, Jia L , et al. Meta-analysis of the effectiveness of trolamine for preventing and treating radiation dermatitis and quality evaluation of GRADE evidence[J]. China Pharm, 2019,30(2):258-263.
[8] Antonadou D, Pepelassi M, Synodinou M, et al. Pro-phylactic use of amifostine to prevent radiochemo-therapy-induced mucositis and xerostomia in head-and-neck cancer[J]. Int J Radiat Oncol Biol Phys, 2002,52(3):739-747.
doi: 10.1016/s0360-3016(01)02683-9 pmid: 11849797
[9] 徐鹭英, 潘建基, 杨凌, 等. 氨磷汀减少鼻咽癌放射治疗中唾液腺损伤的临床研究[J]. 福建医药杂志, 2003,25(4):61-62.
Xu LY, Pan JJ, Yang L , et al. Clinical study of ami-fostine in reducing salivary gland injury in radio-therapy of nasopharyngeal carcinoma[J]. Fujian Med J, 2003,25(4):61-62.
[10] Jellema AP, Slotman BJ, Muller MJ, et al. Radiothe-rapy alone, versus radiotherapy with amifostine 3 times weekly, versus radiotherapy with amifostine 5 times weekly: a prospective randomized study in squamous cell head and neck cancer[J]. Cancer, 2006,107(3):544-553.
pmid: 16804929
[11] Buentzel J, Micke O, Adamietz IA, et al. Intravenous amifostine during chemoradiotherapy for head-and-neck cancer: a randomized placebo-controlled phase Ⅲ study[J]. Int J Radiat Oncol Biol Phys, 2006,64(3):684-691.
pmid: 16243440
[12] 高玉伟, 尹立杰, 丁田贵, 等. 氨磷汀减轻头颈部恶性肿瘤放疗损伤的临床观察[J]. 中国肿瘤临床与康复, 2012,19(6):499-501.
Gao YW, Yin LJ, Ding TG , et al. Clinical treatment of amifostine reduces radiation injury on head and neck cancer[J]. Chin J Clin Oncol Rehabilitation, 2012,19(6):499-501.
[13] Wasserman TH, Brizel DM, Henke M, et al. Influence of intravenous amifostine on xerostomia, tumor con-trol, and survival after radiotherapy for head-and-neck cancer: 2-year follow-up of a prospective, randomized, phase Ⅲ trial[J]. Int J Radiat Oncol Biol Phys, 2005,63(4):985-990.
doi: 10.1016/j.ijrobp.2005.07.966 pmid: 16253773
[14] Lee MG, Freeman AR, Roos DE, et al. Randomized double-blind trial of amifostine versus placebo for radiation-induced xerostomia in patients with head and neck cancer[J]. J Med Imaging Radiat Oncol, 2019,63(1):142-150.
pmid: 30461207
[15] 韩鹏炳, 冀雪娟, 高力英, 等. 氨磷汀对鼻咽癌放射治疗中唾液腺功能的保护作用[J]. 中国辐射卫生, 2019,28(1):98-101.
Han PB, Ji XJ, Gao LY , et al. Protective effect of amifostine on salivary gland function in radiotherapy of nasopharyngeal carcinoma[J]. Chin J Radiol Heal, 2019,28(1):98-101.
[16] 王聪. 131I治疗DTC时维生素C和氨磷汀对唾液腺保护作用研究 [D]. 太原: 山西医科大学, 2016.
Wang C . A comparative study of the protective effect of vitamin C and amifostine to salivary gland function of differentiated thyroid cancer after application 131I [D]. Taiyuan: Shanxi Medical University, 2016.
[17] Cohen EE, LaMonte SJ, Erb NL, et al. American cancer society head and neck cancer survivorship care guideline[J]. CA Cancer J Clin, 2016,66(3):203-239.
pmid: 27002678
[18] Likhterov I, Ru M, Ganz C, et al. Objective and sub-jective hyposalivation after treatment for head and neck cancer: long-term outcomes[J]. Laryngoscope, 2018,128(12):2732-2739.
doi: 10.1002/lary.27224 pmid: 30325025
[19] Schuchter LM, Hensley ML, Meropol NJ, et al. 2002 update of recommendations for the use of chemothe-rapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Onco-logy[J]. J Clin Oncol, 2002,20(12):2895-2903.
doi: 10.1200/JCO.2002.04.178 pmid: 12065567
[20] Ma SJ, Rivers CI, Serra LM, et al. Long-term out-comes of interventions for radiation-induced xeros-tomia: a review[J]. World J Clin Oncol, 2019,10(1):1-13.
doi: 10.5306/wjco.v10.i1.1 pmid: 30627521
[21] Sasse AD, Clark LG, Sasse EC, et al. Amifostine reduces side effects and improves complete response rate during radiotherapy: results of a meta-analysis[J]. Int J Radiat Oncol Biol Phys, 2006,64(3):784-791.
pmid: 16198504
[22] Gu JD, Zhu SW, Li XB, et al. Effect of amifostine in head and neck cancer patients treated with radiothe-rapy: a systematic review and meta-analysis based on randomized controlled trials[J]. PLoS One, 2014,9(5):e95968.
pmid: 24788761
[23] Riley P, Glenny AM, Worthington HV, et al. Inter-ventions for preventing oral mucositis in patients with cancer receiving treatment: cytokines and growth factors[J]. Cochrane Database Syst Rev, 2017, 11: CD011990.
pmid: 30484282
[24] 朱秋霞, 张振勇, 吴荣. 阿米福汀在头颈肿瘤放疗中的应用进展[J]. 医学综述, 2014,20(4):662-665.
Zhu QX, Zhang ZY, Wu R . Research progress in ap-plication of amifostine in radiotherapy of head and neck tumor[J]. Med Recapitul, 2014,20(4):662-665.
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[3] Chen Xiaoli,Zhang Fan,Liu Chengcheng. Application progress on photobiomodulation in the prevention and treatment of oral complications after radiothe-rapy [J]. Int J Stomatol, 2022, 49(6): 707-716.
[4] Li Hongfang,Chen Zhong,Zhang Suxin.. Research progress on immune checkpoint inhibitor combined with radiotherapy in head and neck squamous cell carcinoma [J]. Int J Stomatol, 2022, 49(5): 614-620.
[5] Chen Dong,Yang Zheng,Jiang Li. Research progress on the evaluation and management of radiation-induced xerostomia [J]. Int J Stomatol, 2019, 46(6): 711-717.
[6] Liu Pan1, Duolikun?Wufuer1, Cai Zhigang2, Sun Jian3. Clinical significance of serum squamous cell carcinoma antigens in Uyghur patients with oral squamous cell carcinoma [J]. Inter J Stomatol, 2016, 43(6): 645-650.
[7] Lü Danni, Li Ronglin, Yang Guangwei, Li Chunyang. Prevention and treatment of radiation- and chemotherapy-induced oral mucositis [J]. Inter J Stomatol, 2015, 42(2): 177-180.
[8] Chen Qi, Wu Yun. Therapeutic evaluation of Zhongtongan in the treatment of temporomandibular joint pain after radiotherapy [J]. Inter J Stomatol, 2015, 42(1): 24-27.
[9] Li Wei, Jiang Wen. Head and neck intramuscular myxoma [J]. Inter J Stomatol, 2013, 40(6): 747-749.
[10] WANG Ya-min, SONG Guang-bao.. The effects of radiotherapy on oral implantation [J]. Inter J Stomatol, 2011, 38(2): 204-206.
[11] XIA Yong, NONG Xiao-lin. Advances in treatment of salivary gland malignant tumor [J]. Inter J Stomatol, 2009, 36(1): 46-46～49.
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