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ORIGINAL ARTICLE
Year : 2015  |  Volume : 11  |  Issue : 6  |  Page : 222-225

Metronidazole amino acidum natrium combined with radiation in the treatment of nasopharyngeal carcinoma: A meta-analysis based on randomized controlled trials


Department of Otolaryngology, Head and Neck Surgery, Tianjin Union Medicine Centre, Tianjin 300000, PR, China

Date of Web Publication26-Oct-2015

Correspondence Address:
Shengli Wei
Department of Otolaryngology, Head and Neck Surgery, Tianjin Union Medicine Centre, Tianjin 300000
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.168190

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 > Abstract 

Objective: We performed this meta-analysis to assess the metronidazole amino acidum natrium combined with radiation in the treatment of nasopharyngeal carcinoma.
Materials and Methods: Two reviewers independently reviewed the databases of PubMed and CNKI. The prospective, randomized, controlled trials of metronidazole amino acidum natrium combined with radiation versus radiotherapy alone in the treatment of nasopharyngeal carcinoma were included in this meta-analysis. The objective response rate (RR) of 1-, 3-, and 5-year survival rates were pooled by statistical software. The publication bias was evaluated by Begg's funnel plot.
Results: Sixteen prospective, randomized, controlled trials were finally included in this meta-analysis. The quality assessment showed that the method's quality was relatively poor. The pooled results showed that the metronidazole amino acidum natrium combined with radiation can significantly improve the objective RR for the primary lesion (RR = 1.37, 95% confidence interval [CI]: 1.23–1.53, P < 0.05) and neck metastasis lesion (RR = 1.36, 95% CI: 1.25–1.49, P < 0.05). For survival analysis, the combined treatment can significantly improve the 1-year survival (RR = 1.57, 95% CI: 1.28–1.93, P < 0.05), 3-year survival (RR = 1.23, 95% CI: 1.06–1.41, P < 0.05), and 5-year survival rates (RR = 1.27, 95% CI: 1.05–1.53, P < 0.05).
Conclusion: Metronidazole amino acidum natrium combined with radiation can improve the objective RR and long-term survival compared to radiation therapy alone in the treatment of nasopharyngeal carcinoma.

Keywords: Meta-analysis, metronidazole amino acidum natrium, nasopharyngeal carcinoma, radiation


How to cite this article:
Wei S, Xing Y, Liu J, Wang L, Yang X, Song F, Yang C, Niu L, Yang Y, Wu F. Metronidazole amino acidum natrium combined with radiation in the treatment of nasopharyngeal carcinoma: A meta-analysis based on randomized controlled trials. J Can Res Ther 2015;11, Suppl S2:222-5

How to cite this URL:
Wei S, Xing Y, Liu J, Wang L, Yang X, Song F, Yang C, Niu L, Yang Y, Wu F. Metronidazole amino acidum natrium combined with radiation in the treatment of nasopharyngeal carcinoma: A meta-analysis based on randomized controlled trials. J Can Res Ther [serial online] 2015 [cited 2019 Dec 16];11:222-5. Available from: http://www.cancerjournal.net/text.asp?2015/11/6/222/168190


 > Introduction Top


It was reported that about 60–70% of nasopharyngeal carcinoma was at the advanced stage during the diagnosis.[1] The treatment modality for the advanced or metastasis stage patients was, generally, radiation. However, the average 5-year overall survival rate for radiotherapy was only 30–50%.[2] The main reason for treatment failure was local recurrence or remote metastasis. Hence, how to improve the radiation efficacy and prolong the 5-year survival is important for nasopharyngeal carcinoma treatment.

Recently, several studies have demonstrated that the metronidazole amino acidum natrium combined radiotherapy can improve the prognosis of nasopharyngeal carcinoma. Metronidazole amino acidum natrium is a kind of drug that was developed in China, which could be used as the radiotherapy sensitization agent. It had been proved that the metronidazole amino acidum can improve the radiation effects in patients with nonsmall cell lung cancer.[3] However, the radiotherapy sensitization effects in the patients of nasopharyngeal carcinoma was not conclusive. Thus, we perform this meta-analysis by pooling the open published, prospective, randomized controlled trials in order to assess the efficacy of metronidazole amino acidum natrium combined with radiation in the treatment of nasopharyngeal carcinoma.


 > Materials and Methods Top


Two reviewers (Shengli Wei and Yizhuo Xing) independently reviewed the databases of PubMed and CNKI. The prospective, randomized, controlled trials of metronidazole amino acidum natrium combined with radiation versus radiotherapy alone in the treatment of nasopharyngeal carcinoma were included in this meta-analysis. The inclusion criteria of the studies were: (1) The study type was prospective, randomized controlled trials; (2) the patients who were diagnosed of nasopharyngeal carcinoma; (3) the treatment method was metronidazole amino acidum natrium combined with radiation versus radiotherapy alone (4) the outcomes were objective response rate (RR) and survival. The data for each individual study were extracted by two reviewers (Jixiang Liu and Lin Wang) and checked by the third reviewer (Xiangli Yang).

Statistical analysis

In this meta-analysis, we used the statistical software Stata version 10.0 (http://www.stata.com; Stata Co., College Station, TX, USA) to do all the data analysis. The data were pooled by random or fixed effect model according to the heterogeneity across the included studies. The publication was evaluated by Begg's funnel plot and Egger's line regression test. Two-tailed P < 0.05 was deemed as statistical significance.


 > Results Top


General characteristics

Sixteen prospective, randomized controlled trials [4],[5],[6],[7],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] were finally included in this meta-analysis. All of the studies are published in Chinese. The publication year ranges from 2006 to 2102. The methodology assessment showed that 5 studies mentioned the adequate sequence generation, 2 articles using the allocation concealment, only 1 study mentioned the blinding method, 9 trials mentioned the incomplete outcome data address, and

6 studies reported the free of selecting reporting. The general quality of the included 16 studies was relative poor [Figure 1].
Figure 1: The quality assessment of the 16 studies

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Treatment efficacy

Ten studies reported the objective RR between metronidazole amino acidum natrium combined with radiation and radiotherapy alone. The pooled results showed that the metronidazole amino acidum natrium combined with radiation can significant improve the objective RR for the primary lesion (RR = 1.37, 95% confidence interval [CI]: 1.23–1.53, P < 0.05) and neck metastasis lesion (RR = 1.36, 95% CI: 1.25–1.49, P < 0.05) [Figure 2].
Figure 2: The forest plot for efficacy of metronidazole amino acidum natrium combined with radiation and radiotherapy alone in the treatment of nasopharyngeal carcinoma

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Survival analysis

Three articles reported the 1-year survival, 2 articles reported the 3- and 5-year survival in the combined and radiation therapy alone. The pooled data showed that the combined treatment can significantly improve the 1-year survival (RR = 1.57, 95% CI: 1.28–1.93, P < 0.05), 3-year survival (RR = 1.23, 95% CI: 1.06–1.41, P < 0.05), and 5-year survival rates (RR = 1.27, 95% CI: 1.05–1.53, P < 0.05) [Figure 3].
Figure 3: Forest plot for the survival of metronidazole amino acidum natrium combined with radiation and radiotherapy alone in the treatment of nasopharyngeal carcinoma of chemotherapy-related toxicities

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Publication bias

The publication bias was evaluated by Begg's funnel plot and Egger's line regression test. For an objective response, the funnel plot was asymmetrical [Figure 4] and Egger's test indicated obvious publication bias (P < 0.05). For survival analysis, the Begg's funnel [Figure 5] and Egger's line regression test also indicated significant publication bias (P < 0.05).
Figure 4: The funnel plot for the evaluation of publication bias of objective response

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Figure 5: The funnel plot for the evaluation of publication bias of survival rates

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 > Discussion Top


In this meta-analysis, we finally included 16 prospective, randomized controlled trials. All of the included trials are published in Chinese. We evaluated the quality of the included studies according to Cochrane Handbook.[20] The methodology assessment showed that 5 studies mentioned the adequate sequence generation, 2 articles using the allocation concealment, only 1 study mentioned the blinding method, 9 trials mentioned the incomplete outcome data address, and 6 studies reported the free of selecting reporting. Generally speaking, the quality of the included 16 studies was relatively poor. The poor individual study quality made the results limited.

We pooled the objective RR and survival according to the individual data. The pooled results showed that the metronidazole amino acidum natrium combined with radiation can significantly improve the objective RR for the primary lesion and neck metastasis lesion. The results indicated that the short-term response could be significantly improved by adding the metronidazole amino acidum natrium in the radiation procedure. Moreover, for survival analysis, metronidazole amino acidum natrium combined with radiation can significantly improve the 1-, 3-, and 5-year survival rates. This indicated that the long-term survival could also be improved by the combined treatment.

Although the metronidazole amino acidum natrium combined with radiation can improve the objective response rate and long-term survival compared to radiation therapy alone. However, some limitations were also existed in this meta-analysis: (1) The methodology quality of the included 16 trials was relative poor; (2) all of the studies were came from China with publication language of Chinese; (3) the patients' number in each individual study was relatively small; (4) the drug-related toxicities were not evaluated in this meta-analysis; (5) significant publication bias was found in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

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Huang DP. Epidemiology of nasopharyngeal carcinoma. Ear Nose Throat J 1990;69:222-5.  Back to cited text no. 1
    
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Ren W, Li Z, Mi D, Yang K, Tian J, Zhang Z. A meta analysis of radiosensitivity on non-small cell lung cancer by metronidazole amino acidum natrium. Zhongguo Fei Ai Za Zhi 2012;15:340-7.  Back to cited text no. 3
    
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Liwei Z, Juan Z. Clinical study of the short-term curative effect of CMNa on nasopharyngeal cancer radiotherapy. Int J Clin Exp Med 2008;7:39-40.  Back to cited text no. 4
    
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Jiemei T, Mingyi L, Xiaofan D. The role of sodium glycididazole and its safety in combination with radiotherapy for nasopharyngeal carcinoma. J Youjiang Med Coll Natl 2006;28:533-5.  Back to cited text no. 7
    
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Jiemei T, Mingyi L, Daren L. Radiosensitization of sodium glycididazole in re-radiotherapy for local current nasopharyngeal carcinoma. Mod Med J China 2008;10:25-7.  Back to cited text no. 8
    
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Sihui L. A clincial observation of metronidazole amino acidum natrium combined with radiation in the treatment of nasopharyngeal carcinoma. Guangxi Med J 2008;30:27-8.  Back to cited text no. 9
    
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Mengzhong L, Liru H, Taixiang L, Jiaxiang W. Effect of hypoxic radiosensitizer sodium glycididazole on long-term result of radiotherapy for nasopharyngeal carcinoma. Chin J Oncol 2006;28:932-7.  Back to cited text no. 10
    
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Shuang W, Jialin Y, Zhilin L, Yaogang L. Radiosensitivity on nasopharyngeal carcinoma by CMNa. Cancer Res Prev Treat 2006;33:200-1.  Back to cited text no. 11
    
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Rong L, Xiang S, Xinhong C, Zhonghua X. Radiosensi tization of CMNa for locally recurrent nasopharyngeal cancer. Cancer Res Prev Treat 2008;21:162-4.  Back to cited text no. 12
    
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Shibi Z, Qinghua J, Mei C, Wanqin Z. Observation and nursing of the treatment of NPC by glycididazole sodium combined with radiotherapy. Cancer Res Prev Treat 2008;21:315-7.  Back to cited text no. 13
    
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Yongbi W, Yuanhe T, Jianwen L, Dongping L. A clincial observation of metronidazole amino acidum natrium combined with radiation in the treatment of stage III nasopharyngeal carcinoma. Strait Pharm J 2010;22:172-4.  Back to cited text no. 14
    
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Shaobing L, Ming L, Yufei P, Baihui L. Clinical study of CMNa combined with radiotherapy on advanced nasopharyngeal carcinoma. J Mod Oncol 2010;18:2137-8.  Back to cited text no. 15
    
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Yong Y, Xiulin T, Junping H, Wenbing S. Metronidazole amino acidum natrium combined with radiation in the treatment of elder patients with nasopharyngeal cancer. Chin J Gerontol 2012;32:2890-1.  Back to cited text no. 16
    
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Wenhui Z, Xiuhua P, Xiaoxia B, Xiaocong J. Effect assessment of sodium glycididazo combined with radiation treatment of nasopharyngeal cancer. J Aerosp Med 2011;22:389-90.  Back to cited text no. 17
    
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Lu Z. Glycididazole sodium used as an hypoxic tumor cell radiosensitizer in the treatment for recurrence of nasopharyngeal carcinoma. China Mod Doct 2009;47:15-6, 51.  Back to cited text no. 18
    
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Wanhong G, Xiaoguang Y, Jing C, Zhilong W, Guodong X. The clinical observation of sodium glycididazole (CMNa) on enhancement of radiation sensitivity for nasopharyngeal cancer. J Basic Clin Oncol 2009;22:134-6.  Back to cited text no. 19
    
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McKenzie JE, Salanti G, Lewis SC, Altman DG. Meta-analysis and the Cochrane collaboration: 20 years of the Cochrane Statistical Methods Group. Syst Rev 2013;2:80.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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