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Meta-Analysis
. 2016 Sep;15(3):285-307.
doi: 10.1177/1534735416638738. Epub 2016 May 4.

Chinese Herbal Medicine and Fluorouracil-Based Chemotherapy for Colorectal Cancer: A Quality-Adjusted Meta-Analysis of Randomized Controlled Trials

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Free PMC article
Meta-Analysis

Chinese Herbal Medicine and Fluorouracil-Based Chemotherapy for Colorectal Cancer: A Quality-Adjusted Meta-Analysis of Randomized Controlled Trials

Michael McCulloch et al. Integr Cancer Ther. .
Free PMC article

Abstract

Background Chinese herbal medicines reportedly increase efficacy and minimize toxicity of chemotherapy; however, little attention has been paid to how poor study quality can bias outcomes. Methods We systematically searched MEDLINE, TCMLARS, EMBASE, and Cochrane Library for randomized controlled trials of Chinese herbal medicines combined with fluorouracil-based chemotherapy compared with the same chemotherapy alone. We screened for eligibility, extracted data, and pooled data with random-effects meta-analysis. Outcome measures were survival, toxicity, tumor response, performance status, quality of life, and Cochrane Risk of Bias (ROB) criteria to critically evaluate the quality of reporting in the randomized trials included in the meta-analysis. Results We found 36 potentially eligible studies, with only 3 (those with low ROB) qualifying for meta-analysis. Two reported chemotherapy-related diarrhea reduced by 57% (relative risk [RR] = 0.43; 95% CI = 0.19-1.01; I(2) test for variation in RR due to heterogeneity = 0.0%), with nonsignificant results. Two reported white blood cell toxicity reduced by 66% (RR = 0.34; 95% CI = 0.16-0.72; I(2) test for variation in RR due to heterogeneity = 0.0%), with statistically significant results. Stratifying analysis by studies with high versus low ROB, we found substantial overestimation of benefit: Studies with high ROB overestimated by nearly 2-fold reduction of platelet toxicity by Chinese herbal medicines (RR = 0.35, 95% CI = 0.15-0.84 vs RR = 0.65, 95% CI = 0.11-3.92). Studies with high ROB overestimated by nearly 2-fold reduction of vomiting toxicity (RR = 0.45, 95% CI = 0.33-0.61 vs RR = 0.87, 95% CI = 0.48-1.58). And, studies with high ROB overestimated by 21% the reduction in diarrhea toxicity (RR = 0.34, 95% CI = 0.20-0.58 vs RR = 0.43, 95% CI = 0.19-1.01). Studies with high ROB also overestimated by 16% improvement in tumor response (RR = 1.39, 95% CI = 1.18-1.63 vs RR = 1.20; 95% CI = 0.81-1.79). Not accounting for ROB would have exaggerated evidence of benefit and failed to detect nonsignificance of results. Conclusions In the present analysis, involving 36 studies, 2593 patients, 20 outcomes, 36 medical institutions, and 271 named research authors, 92% of the data points were from studies at high ROB. Given the poor quality of the data in studies identified, it cannot be concluded whether combining Chinese herbs with chemotherapy reduces toxicity of chemotherapy.

Keywords: Chinese herbal medicine; chemotherapy; colorectal cancer; meta-analysis; performance status; survival.

Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Flow diagram. RCT, randomized controlled trial. Note: In the RCTs Excluded box, 1 study had more than 1 reason for being excluded, therefore while the individual reasons total 22, the number of studies excluded is 21.
Figure 2.
Figure 2.
Reduction in diarrhea toxicity. Note: Vertical dashed line indicates the effect size in this analysis.
Figure 3.
Figure 3.
Reduction in platelet toxicity. Note: Vertical dashed line indicates the effect size in this analysis.
Figure 4.
Figure 4.
Reduction in vomiting toxicity. Note: Vertical dashed line indicates the effect size in this analysis.
Figure 5.
Figure 5.
Reduction in white blood cell (WBC) toxicity. Note: Vertical dashed line indicates the effect size in this analysis.
Figure 6.
Figure 6.
Increase in objective tumor response. Note: Vertical dashed line indicates the effect size in this analysis.

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