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Journal of Integrative Medicine ›› 2014, Vol. 12 ›› Issue (4): 346-358.doi: 10.1016/S2095-4964(14)60034-0

• Systematic Review • Previous Articles     Next Articles

Traditional Chinese medicinal herbs combined with epidermal growth factor receptor tyrosine kinase inhibitor for advanced non-small cell lung cancer: A systematic review and meta-analysis

Zhong-liang Liua, Wei-rong Zhub, Wen-chao Zhouc, Hai-feng Yingb, Lan Zhengb, Yuan-biao Guob, Jing-xian Chenb, Xiao-heng Shenb   

  1. a Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
    b Department of Traditional Chinese Medicine, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 210000, China
    c Department of Science and Technology, Putuo District Central Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China
  • Received:2014-01-25 Accepted:2014-04-15 Online:2014-07-10 Published:2014-07-15

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Background

Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted treatment has been a standard therapy for advanced non-small cell lung cancer (NSCLC), but it is not tolerated well by all patients. In China, some studies have reported that traditional Chinese medicinal herbs (TCMHs) may increase efficacy and reduce toxicity when combined with EGFR-TKI, but outside of China few studies of this kind have been attempted. 

Objective

This study is intended to systematically review the existing clinical evidence on TCMHs combined with EGFR-TKI for treatment of advanced NSCLC. 

Search Strategy

PubMed, the Cochrane Library, the Excerpta Medica Database (EMBASE), the China BioMedical Literature (CBM), and the China National Knowledge Infrastructure (CNKI) and web site of the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the World Conference of Lung Cancer (WCLC) were searched; the search included all documents published in English or Chinese before October 2013. 

Inclusion Criteria

We selected randomized controlled trials based on specific criteria, the most important of which was that a TCMH plus EGFR-TKI treatment group was compared with an EGFR-TKI control group in patients with advanced NSCLC. 

Data Extraction and Analysis

The modified Jadad scale was used to assess the quality of studies. For each included study, patient characteristics, treatment details, therapeutic approach and clinical outcomes were collected on a standardized form. When disagreements on study inclusion or data extracted from a study emerged, the consensus of all coauthors provided the resolution. The clinical outcome metrics consisted of objective response rate (ORR; complete response + partial response divided by the total number of patients), disease control rate (DCR; complete response + partial response + no change divided by the total number of patients), survival rate, improved or stabilized Karnofsky performance status (KPS), and severe toxicity. RevMan 5.0 software was used for data syntheses and analyses. Risk ratio (RR) and 95% confidence interval (CI) were calculated; if the hypothesis of homogeneity was not rejected (P>0.1, I2<50%), the fixed-effect model was used to calculate the summary RR and the 95% CI. Otherwise, a random-effect model was used. 

Results

In this review, 19 studies were included based on the selection criteria. Of them, 13 studies were of high quality and 6 studies were of low quality, according to the modified Jadad scale. When the TCMH plus EGFR-TKI treatment groups were compared with the EGFR-TKI control groups the meta-analysis demonstrated a statistically significant higher ORR (RR 1.34; 95% CI 1.15 to 1.57; P=0.000 2), DCR (RR 1.18; 95% CI 1.09 to 1.27; P<0.000 1), one-year survival rate (RR 1.21; 95% CI 1.01 to 1.44; P=0.04), 2-year survival rate (RR 1.91; 95% CI 1.26 to 2.89; P=0.002) and improved or stable KPS (RR 1.38; 95% CI 1.26 to 1.51; P<0.000 01). Severe toxicity for rash was decreased (RR 0.55; 95% CI 0.32 to 0.94; P=0.03), as were nausea and vomiting (RR 0.17; 95% CI 0.04 to 0.72; P=0.02) and diarrhea (RR 0.46; 95% CI 0.24 to 0.89; P=0.02). Sensitivity analysis indicated that findings of the meta-analysis were robust to study quality. In the funnel plot analysis, asymmetry was observed, and publication bias was indicated by Egger’s test (P=0.03). 

Conclusion

TCMH intervention can increase efficacy and reduce toxicity when combined with EGFR-TKI for advanced NSCLC, although this result requires further verification by more well designed studies.

Key words: Drugs, Chinese herbal, Receptor, Epidermal growth factor, Protein-tyrosine kinases, Non-small cell lung cancer, Randomized controlled trials, Review, Meta-analysis

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Figure 1

Flow chart of study selection in this review EMBASE: the Excerpta Medica Database; CBM: the China BioMedical Literature; ASCO: the American Society of Clinical Oncology; ESMO: the European Society for Medical Oncology; WCLC: the World Conference of Lung Cancer; CNKI: the China National Knowledge Infrastructure."

Figure 2

Forest plot of the risk ratio for objective response rateThe squares and horizontal lines correspond to the study-specific risk ratio and 95% CI. The area of the squares reflects the weight (Mantel-Haenszel). The diamond represents the summary risk ratio and 95% CI."

Figure 3

Forest plot of the risk ratio for disease control rateThe squares and horizontal lines correspond to the study-specific risk ratio and 95% CI. The area of the squares reflects the weight (Mantel-Haenszel). The diamond represents the summary risk ratio and 95% CI."

Figure 4

Forest plot of the risk ratio for survival rateThe squares and horizontal lines correspond to the study-specific risk ratio and 95% CI. The area of the squares reflects the weight (Mantel-Haenszel). The diamond represents the summary risk ratio and 95% CI."

Figure 5

Forest plot of improved or stable Karnofsky performance scoreThe squares and horizontal lines correspond to the study-specific risk ratio and 95% CI. The area of the squares reflects the weight (Mantel-Haenszel). The diamond represents the summary risk ratio and 95% CI."

Figure 6

Forest plot of grade 3 or 4 rashThe squares and horizontal lines correspond to the study-specific risk ratio and 95% CI. The area of the squares reflects the weight (Mantel-Haenszel). The diamond represents the summary risk ratio and 95% CI."

Figure 7

Forest plot of grade 3 or 4 diarrhea, and nausea and vomitingThe squares and horizontal lines correspond to the study-specific risk ratio and 95% CI. The area of the squares reflects the weight (Mantel-Haenszel). The diamond represents the summary risk ratio and 95% CI."

"

Figure 8

Funnel plot based on studies with data on objective tumor response rateIf the data are biased, there will be asymmetrical funnel plot asymmetry; the more obvious, the greater the degree of bias. Funnel plot asymmetry is primarily related to publication bias, but there may be other reasons."

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Journal of Integrative Medicine, ISSN: 2095-4964 CN 31-2083/R
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