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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 5  |  Page : 56-59

Herbal extract elemene intrathoracic injection in the treatment of lung cancer patients with malignant pleural effusion: A meta-anaylsis


1 Department of Respiratory, People's Hospital of Changshan, Quzhou, China
2 Department of Clinical Medicine, Lishui People's Hospital, Zhejiang Province, China

Date of Web Publication30-Aug-2014

Correspondence Address:
Ming-Dong Wu
Department of Clinical Medicine, Lishui People's Hospital Zhejiang Province - 323 000
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.139761

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 > Abstract 

Objective: The aim of this study was to evaluate the clinical efficacy of elemene intrapleural injection in the treatment of lung cancer with malignant pleural effusion by meta-analysis.
Materials and Methods: PubMed (1960-2014.4), EMBASE (1980-2014.4) and CNKI (1979-2014.4) data bases were searched to identify the randomized controlled trials about elemene intrapleural injection in the treatment of malignant pleural effusion caused by lung cancer. The relativel risk (RR) was used to evaluated the the clinical efficacy of elemene intrapleural injection in the treatment of pleural effusion compared to other drugs.
Results: A total of 1298 subjects with 14 studies were finally included in this meta-analysis. Meta-analysis showed that the objective response rate (ORR) in elemene group was much higher than that in other drugs group (RR =1.20, 95% CI:1.05-1.37, P = 0.008). We performed the sub-groups analysis according to the drugs used in the control group. And the subgroup analyzed demonstrated that the ORR in elemene group was higher than that in Cisplatin (DDP) and high sugar group with statistical difference (P < 0.05). But no statistical difference was found in the bleomycin and interleukin-2 [IL-2] subgroups (P > 0.05).
Conclusion: High clinical efficacy of elemene was found in the treatment malignant pleural effusion in patients with lung cancer.

Keywords: Elemene, lung cancer, meta-analysis, pleural effusion


How to cite this article:
Chen J, Chen YJ, Wu MD. Herbal extract elemene intrathoracic injection in the treatment of lung cancer patients with malignant pleural effusion: A meta-anaylsis. J Can Res Ther 2014;10, Suppl S1:56-9

How to cite this URL:
Chen J, Chen YJ, Wu MD. Herbal extract elemene intrathoracic injection in the treatment of lung cancer patients with malignant pleural effusion: A meta-anaylsis. J Can Res Ther [serial online] 2014 [cited 2021 Feb 24];10:56-9. Available from: https://www.cancerjournal.net/text.asp?2014/10/5/56/139761


 > Introduction Top


Lung cancer, accounting for 1.4 million deaths world-wide in year 2008, was the first leading cause of cancer related mortality for male and second for female. [1] It is estimated that a total of 160,300 deaths, 726, 00 in female and 87, 700 in male, will be detected in the year 2012 in the USA. [2] Generally, lung cancer was divided into non-small cell lung carcinoma (NSCLC) and small-cell lung cancer (SCLC) according to their biological behavior. Advanced lung cancer usually cause pleural metastasis which lead to the malignant pleural effusion. Huge malignant pleural effusion need to be treated emergently because of too much pleural effusion can cause difficulty in breathing and hemodynamics. Generally, when pleural effusion was fond in lung cancer patients, the chest drainage procedure was usually performed and then injected the chemotherapy drugs or other immune agents such as bleomycin and proleulzin which could adhere the visceral pleura and partial pleura together. When the visceral pleura and partial pleura was adhered together, the pleural cavity disappeared which could stop the recurrence of malignant pleural effusion. Several drugs were usually used for intrathoracic injection such as elemene, DDP, bleomycin, proleulzin etc. But the clinical efficacy about these drugs for the treatment of malignant effusion in patients with lung cancer was not coincident with each other. [3],[4] Thus, a meta-analysis was performed in order to compare the clinical efficacy of elemene versus other drugs in the treatment of malignant pleural effusion in patients with lung cancer.


 > Materials and methods Top


Search strategy

The search strategy of relevant studies was demonstrated in the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement flow chart [Figure 1]. The randomized controlled trials (RCTs) comparing elemene and other drugs in intrthoracic injection in the treatment of malignant effusion in patients with lung cancer were search across an electronic sensitive search of Medline, the Cochrane central register of controlled trials, EMBASE and CNKI databases. The search terms were used as: "lung cancer", "lung carcinoma", "carcinoma of the lung", "elemene", "pleural effusion". Searches were limited to human trials, with the language restriction of English and Chinese. All references of relevant articles were scanned for additional analysis.
Figure 1: Forest plot of elemene intrathoracic injection in the treatment of malignant pleural effusion

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Selection criteria

Details of the patients' general characteristics, treatment regimen and outcomes of the relevant studies were extracted by two reviewer (JC and YJ) and then checked by the third reviewer (MWu) as described by the Cochrane Handbook for systematic reviews. [5] The patients included in the relevant studies were limited to lung cancer with malignant pleural effusion. The intervention was intrathoracic injection of elemene and the control was intrathoracic injection of drugs other than elemene. The outcomes were restricted to complete response and partial response for the treatment of malignant pleural effusion.

Data extraction and quality assessment

Data was extracted by JC and YJ independently from all included studies. The general characteristics such as first author, year of publication, number of patients in each arm, and regimens were extracted for each of the trials. The complete and partial response rate in each study was also extracted by which the pooled risk ratio (RR) could be calculated.

Statistical analysis

Stata/SE 11.0 (StataCorp LP, http://www.stata.com) statistical software were used to conduct the statistical analysis. Dichotomous data are calculated as the RR with the 95% confidence interval (CI). Statistical heterogeneity of objective response rate across trials was assessed by chi-square (χ2 ) test, [6] and the inconsistency was calculated by I 2 . [7] If heterogeneity was found (χ2 , P < 0.05 or I 2 > 50%), the random-effect method (Dersimonian-Laird method) was used to pool the data and subgroups analysis was done for further evaluation. Inversely, without significant heterogeneity, fixed-effect method was considered. The Egger's tests were used for each effect size to evaluate possible publication bias as described by Egger. [8]


 > Results Top


Study characteristics

Thorough searching the electronic databases, 14 trails [3],[4],[8],[9],[10],[11],[12],[13],[14],[15],[16],[17],[18],[19] including a total of 1298 subjects were finally included in this meta-analysis. The detailed selection procedure was showed in [Figure 1]. Of the included 14 trails, nine studies used DDP as the control regimen, three used bleomycin as the control regimen and two used other drugs. And the general characteristics of included studies were summarized in [Table 1].
Table 1: The general characteristics of the included studies


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Pooled results of the meta-analysis

The objective response rate range from 56%-100% in elemene group and 38%-78% in the control group respectively [Figure 1]. The pooled results demonstrated that the objective response rate (ORR) in elemene group was much higher than that in control group (RR =1.20, 95%, CI:1.05-1.37, P = 0.008), [Figure 2].
Figure 2: Objective response distribution in the elemene and control groups

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Sub-group analysis

We performed the sub-group analysis according to the drug type used in the control group. The sub-group analysis showed that the ORR in elemene group was higher than that in DDP and high sugar group with statistical difference (P < 0.05). But no statistical difference was found in the bleomycin and interleukin-2 [IL-2] subgroups (P > 0.05), [Figure 1].

Publication bias

Begger's funnel plot and Egger's liner regression tests were used to evaluate the publication bias of this meta-analysis. [20] The funnel plot [Figure 3] demonstrated a little bit asymmetry at the bottom of the X axis. However, Egger's test does not show any evidence of statistical publication bias (t = -1.05, P =0.31).
Figure 3: Begger's funnel plot for publication bias evaluation

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 > Discussion Top


Lung cancer is leading cause of cancer related mortality world-wide with 100 million deaths and 120 million diagnosed in the year 2009 (Jemal et al., 2009). Without effective early diagnosis method, the prognosis of NSCLC is relative poor with a 5-year survival rate of less than 15%. [21] Pleural metastasis was usually caused by advanced lung cancer, which lead to the malignant pleural effusion. Huge malignant pleural effusion needs to be treated emergently because of too much pleural effusion can cause difficulty in breathing and hemodynamics. According to traditional Chinese medicine theory, the malignant pleural effusion belongs to the region of "Xuanyin" which was caused by the "Xiedu" of the body. Elemene intrathoracic injection was always used to control the pleural effusion recurrence in China. [10],[11],[12] Elemene (1-methyl-1-vinyl-2, 4-diisopropenyl- cyclohexane), isolated from the Chinese medicinal herb Curcuma wenyujin, which exhibits antitumor activity in vitro and in vivo.[22] Elemene injection, a wide spectrum antitumor drug with the main ingredient of β-elemene, has been extensively used for treatment of several types of cancers, especially for intrathoracic injection which could inhibit the pleural effusion recurrence.

In our meta-analysis, A total of 1298 subjects with 14 studies were finally included in this meta-analysis. Of the included 14 trials, nine studies used DDP as the control regimen, three used bleomycin as the control regimen and two used other drugs all of the included studies were come from China. Pooled analysis showed that the ORR in elemene group was much higher than that in other drugs group (RR =1.20, 95% CI:1.05-1.37, P = 0.008). The results demonstrated that patients treated with elemene with less pleural recurrence. We performed the sub-groups analysis according to the drugs used in the control group. And the subgroup analyzed demonstrated that the ORR in elemene group was higher than that in DDP and high sugar group with statistical difference (P < 0.05). But no statistical difference was found in the bleomycin and IL-2 subgroups (P > 0.05). The abouve results indicated that high clinical efficacy of elemene was found in the treatment malignant pleural effusion in patients with lung cancer.

The intrathoracic injection of elemene increase the objective respons for treatment of malignant effusion in patients with lung cancer. The reason for the increased clinical efficacy could be explained by the following three aspects: (1) Several studies showed that elemene could enhance the inhibitory effect through a mitochondria dependent apoptosis pathway on the growth of tumor cells in vitro. [23],[24] (2) It has been demonstrated that elemene upregulated heat shock protein 70 and increased the apoptosis of tumor cells (49,50). (3) The elemene improves the function of immune cells. Elemene inhibited the growth of tumor and enhanced cellular immune functions via cytokine production (IL-2 or IL-12) and increase of natural killer (NK) cell activity in tumor-bearing mice (51-53). All of the above mechanism could increase the clinical efficacy for controlling malignant pleural effusion.

However, some limitations of this meta-analysis are needed for further consideration. [25] First, all of the trials were from China, which could lead to selection bias; Second, without long term follow-up, the long term clinical efficacy for elemene intrathoracic injection in the treatment of malignant pleural effusion was not evaluated because of lack of enough individual data. Third, the quality of the included studies was relatively poor.

 
 > References Top

1.Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 1
    
2.Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012;62:10-29.  Back to cited text no. 2
    
3.Lin ST, Qiu QN. A clinical study of elemene in the treatment of advanced lung cancer. Fujian Med J 1996;18:90.  Back to cited text no. 3
    
4.Ye AH, Xia XY. Clinical obversation of elemene in the treatment of pleural effusion. Hebei Med 2001;7:805-6.  Back to cited text no. 4
    
5.Zafarmand MH, van der Schouw YT, Grobbee DE, de Leeuw PW, Bots ML. The M235T polymorphism in the AGT gene and CHD risk: Evidence of a Hardy-Weinberg equilibrium violation and publication bias in a meta-analysis. PLoS One 2008;3:e2533.  Back to cited text no. 5
    
6.DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88.  Back to cited text no. 6
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7.Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.  Back to cited text no. 7
    
8.Jiang LP, Dai YD, Tao L, Wang MX, Li G, He SL. Elemene, bleomycin, as well as the two drugs in the treatment of malignant pleural effusion clinical observation. China Oncol 2009;19:218-20.  Back to cited text no. 8
    
9.Wang P. Clinical observation of B-elemine for treating advance pulmonary carcinoma with pleurorrhea by intrathoracic perfusion. Mod Med Health 2002;18:180-1.  Back to cited text no. 9
    
10.Bai XL. Clinical study of elemene and DDP intrathoracic injection in the treatment of malignant pleural effusion. Mod J Integr Tradit Chin West Med 2005;14:321-2.  Back to cited text no. 10
    
11.Li ZJ, Zhang Y. Elemene combined with chemotherapy in the treatment of lung cancer with malignant pleural effusion. China J Misdiagn 2006;6:3932-3.  Back to cited text no. 11
    
12.Shi GQ. Clinical study of elemene intrathoracic injection for the treatment of malignant pleural effusion. J Pract Diagn Ther 2007;21:373-4.  Back to cited text no. 12
    
13.Wang H, Shi HR, Jia M. Bleomycin combined with elemene in the treatment of malignant pleural effusion in patients with non small cell lung carcinoma. J Med Res 2007;36:108-9.  Back to cited text no. 13
    
14.Wang YJ, Xu N, Sun ZF, Zhao Y, Ma QF.A clinical study of elemene in the treatment of malignant pleural effusion in patients with non-small cell lung carcinoma. Chinese Journal of Misdiagnostics 2009;9:2800-1.  Back to cited text no. 14
    
15.Wang AF, Wang YJ, Cui XF. Elemene versus bleomycin in the treatment of malignant pleural effusion: A clinical study. Strait Pharm J 2011;23:125-6.  Back to cited text no. 15
    
16.Chen SM, Xie H. A clinical observation of elemene combined with proleulzin in the treatment of malignant pleural effusion in patients with non-small cell lung cancer. Qiuyi Wenyao 2012;10:820-1.  Back to cited text no. 16
    
17.Kong YM. A clinical analysis of elemene in the treatment of malignant pleural effusion. J Mod Med Health 2012;28:1521-2.  Back to cited text no. 17
    
18.Wang LD. Observation on the clincal efficacy of elemenum emulsion combined with intrapleural injection of low dose of cisplation for treatment of malignant pleural effusion in patients with lung cancer. J Clin Res 2012;29:1524-5.  Back to cited text no. 18
    
19.Sun LY. Clinical study of elemene intrathoracic injection in the treatment of malignant pleural effusion in patients with lung cancer. Chinese Community Doctors 2012;14:80.  Back to cited text no. 19
    
20.Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629-34.  Back to cited text no. 20
    
21.Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin 2013;63:11-30.  Back to cited text no. 21
    
22.Guo YT. Isolation and identification of elemene fromthe essential oil of Curcuma wenyujin. Zhong Yao Tong Bao 1983;8:31.  Back to cited text no. 22
    
23.Li X, Wang G, Zhao J, Ding H, Cunningham C, Chen F, et al. Antiproliferative effect of beta-elemene in chemoresistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-M phase. Cell Mol Life Sci 2005;62:894-904.  Back to cited text no. 23
    
24.Li QQ, Wang G, Zhang M, Cuff CF, Huang L, Reed E. Beta-Elemene, a novel plant-derived antineoplastic agent, increases cisplatin chemosensitivity of lung tumor cells by triggering apoptosis. Oncol Rep 2009;22:161-70.  Back to cited text no. 24
    
25.Sun H, Guo J, Liu Y, Wang Z. Classification and regression tree analysis of patients with non-small-cell lung cancer treated with gefitinib after chemotherapy. Thoracic Cancer 2013; 4: 280-86.  Back to cited text no. 25
    


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