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JTCM
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Volume 35
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Issue 4
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Online Submissions: http://www.journaltcm.com J Tradit Chin Med 2015 August 15; 35(4): 361-374
info@journaltcm.com ISSN 0255-2922
© 2015 JTCM. All rights reserved.
SYSTEMATIC REVIEW
Effect of Aidi injection plus chemotherapy on gastric carcinoma: a
Meta-analysis of randomized controlled trials
Wang Jiancheng, Ge Long, Zhao Ye, Li Jinlong, Zhang Pan, Mao Lei, Yang Kehu
aa
Wang Jiancheng, Mao Lei, Evidence Based Medical Center
of Lanzhou University, Lanzhou 730000, China
Ge Long, Li Jinlong, The First Clinical Medical College of
Lanzhou University, Lanzhou 730000, China
Zhao Ye, Zhang Pan, School of Basic Medical Science of
Lanzhou University, Lanzhou 730000, China
Yang Kehu, Evidence Based Medical Center of Lanzhou Uni-
versity, Lanzhou 730000, China; Key Laboratory of Evidence
Based Medicine and Knowledge Translation of Gansu Prov-
ince, Lanzhou 730000, China
Correspondence to: Prof. Yang Kehu, Evidence Based Med-
ical Center of Lanzhou University, Lanzhou 730000, China;
Key Laboratory of Evidence Based Medicine and Knowledge
Translation of Gansu Province, Lanzhou 730000, China. ke-
huyangebm2006@163.com
Telephone: +86-931-8915076
Accepted: July 14, 2014
Abstract
OBJECTIVE: To conduct a Meta-analysis of studies
on the effect of Aidi injectioncombined with che-
motherapy versus chemotherapy alone in the treat-
ment of gastric cancer (GC).
METHODS: Nine electronic databases and six gray
literature databases were comprehensively searche-
duntil April 20, 2013. Two reviewers independently
selected and assessed included trialsaccording to
the inclusion and exclusion criteria. The risk of bias
tool from the Cochrane Handbook version 5.1.0
was used to assess trial quality. All calculations
were performed using Review Manager 5.0.
RESULTS: Thirty-two studies including 1927 partici-
pants met the inclusion criteria, most of which
were low quality. Compared with chemotherapy
alone, Aidi injection plusthe same chemotherapy
significantly improved the effective rate [OR = 1.52,
95% CI (1.24, 1.86), P < 0.0001], clinical beneficial
rate [OR = 1.77, 95% CI (1.33, 2.36), P < 0.0001], and
quality of life [OR = 3.02, 95% CI (2.39, 3.82), P <
0.000 01]. There was a significant improvement in
nausea and vomiting incidence [OR = 0.34, 95% CI
(0.24, 0.47), P < 0.000 01], diarrhea [OR = 0.47, 95%
CI (0.33, 0.69), P < 0.000 01], leukopenia ( Ⅲ-Ⅳ)
[OR = 0.34, 95%CI (0.23, 0.51), P = 0.05], hemoglo-
bin decrease (Ⅲ-Ⅳ) [OR = 0.42, 95% CI (0.18-1.00),
P = 0.05], thrombocytopenia (Ⅲ-Ⅳ) [OR = 0.46, 95%
CI (0.22, 0.96), P = 0.04], and damage to liver func-
tion [OR = 0.36, 95%CI (0.24, 0.54), P < 0.000 01].
CONCLUSION: Aidi injection combined with che-
motherapy significantly improved the clinical effect
of chemotherapy, reducing the incidence of ad-
verse events. Use of the CONSORT statement for
randomized controlled trials is recommended for
stricter reporting.
© 2015 JTCM. All rights reserved.
Key words: Drug therapy; Stomach neoplasms; Re-
view; Randomized controlled trial; Aidi injection
INTRODUCTION
Gastric carcinoma (GC) is one of the common malig-
nant carcinomas. GC is the fourth most frequent ma-
lignant cancer and the second most common cause of
death, with an incidence of 989 600 cases and 738 000
deaths worldwide in 2008.
1
More than 70% of new cas-
es and deaths occur in underdeveloped countries.
2
In
China, there were 464 000 new gastric carcinoma cases
and 352 000 deaths in 2008, accounting for 16.5% of
allcancer cases and 18.0% of cancer-related deaths.
3
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Therefore,GC isa largeworldwide publichealthburden.
Surgical therapies, radiotherapies, and chemotherapies
arethe three mainstays of treatment. Unfortunately, al-
most half of the patients that present with mid-
dle-to-advanced stage gastric cancer are inoperable,
with a median survival time (MST) of 6-10 months.
Therefore, comprehensive chemotherapy treatment
programs aremost commonly used for GC.
4
However,
chemotherapy has adverse short- and long-term side ef-
fects,
5
because the selectivity of chemotherapy is low
for normal cells. Traditional Chinese medicinal herbs
combined with chemotherapy could significantly im-
prove quality of life, relieve symptoms, remove toxins,
increase immune function, and act as anticancer
agents.
6
Aidi injection is made from an extraction of Renshen
(Radix Ginseng), Huangqi (Radix Astragali Mongolici),
Ciwujia (Radix et Caulis Acanthopanacis Santicosi), and
Banmao (Mylabri).The injection can clear heat and tox-
ins, remove blood stasis, inhibit tumor growth, induce
apoptosis, decrease the side-effects of radiotherapy and
chemotherapy, and increase immune function.
7,8
Aidi
injection combined with chemotherapy could improve
the effect of chemotherapy, increase drug tolerance,
and improve quality of life.
7
We aimed toconduct a Meta-analysis of 32 random-
ized controlled trials (RCTs) to assess the efficacy and
safety of Aidi injection combined with chemotherapy
in GC patients.
DATA AND METHODS
Study selection
The study search, study selection, data extraction, and
quality assessment were performed independently by
two trained reviewers (JCW and LG). Disagreements
between reviewers were resolved through consensus or
by consulting a third expert adjudicator (KHY).
Inclusion and exclusion criteria
Included studies met the following inclusion criteria:
(a) RCTs using Aidi injection combined with chemo-
therapy for GC patients; (b) participants were con-
firmed to have GC pathologically or via computed to-
mography, regardless of age, sex, or nationality; (c) in-
tervention was Aidi injection combined with chemo-
therapy vschemotherapy alone;and (d) relative risks
(RR), odds ratios (OR), or data for calculations were
provided.
Studies were excluded if: (a) the patients were not con-
firmed to have GC; (b) the studies were not RCTs; (c)
the control measures did not include chemotherapy;
(d) the data could not be extracted; or (e) the study
was a review or Meta-analyses, animal study, case re-
port, conference abstracts, or letters to journal editors.
Outcome measures
Efficiency rate was defined as complete response (CR)
+ partial response (PR), according to the World Health
Organization (WHO)
9
criteria for solid tumors.The
clinical beneficial rate was defined as complete re-
sponse (CR) + partial response (PR) + stable disease
(SD). Quality of life before and after treatment was as-
sessed using the Karnofsky performance status scale
(KPS), with KPS scores increasing by ≥10 points after
treatment considered as improving quality of life, KPS
scores decreasing by ≥ 10 points after treatment as low-
er quality of life, and KPS scores increasing or decreas-
ing by < 10 points considered as stable.
According to the WHO grading criteria for acute and
sub acute toxicity of anticancer drugs,
10
adverse events
were evaluated after treatment,including leukopenia,
thrombocytopenia, nausea/vomiting, anemia, and diar-
rhea. Survival time was calculated from the beginning
of chemotherapy to death, withdrawal, or drop out.
Immune function was measured with T lymphocyte
subsets such as CD3, CD4, CD8, CD4/CD8, and NK
cells before and after treatment.
Search strategy
We comprehensively searched the following databases:
China Academic Journal Network Publishing Data-
base (CAJD, 1994-2013/4), Chinese Biomedical Liter-
ature Database (CBM, 1978-2013/4), Chinese Tech-
nological Periodical Full-text Database (VIP,
1989-2013/4), China Online Journals (COJ,
1997-2013/4), Chinese Science Citation Database
(CSCD, 1989-2013/4-2013/4), PubMed (1966-2013/
4), EMBASE (1974-2013/4), Cochrane Library (incep-
tion-2013/4), and Science Citation Index Expanded
(SCI-EXPANDED, 2000-2013/4). Grey literature was
obtained from the China Proceedings of Conference
Full-text Database (CPCD, 1994-2013/4), Academic
Conferences in China (ACIC, 1990-2013/4), Chi-
nese-foreign Conference Database (via National Sci-
ence and Technology Library, 1985-2013/4), China
Doctoral Dissertations full-text Database (CDFD,
1994-2013/4), China Master's Theses Full-text Data-
base (CMFD, 1994-2013/4), and Dissertations of Chi-
na (DOC, 1990-2013/4). Searches were composed of
a combination of the following terms: stomach neo-
plasm, gastric neoplasm, stomach cancer, gastric can-
cer, stomach neoplasms, Aidi zhusheye, Aidi injection,
Aidi, and random*. The searches were performed on
April 20, 2013. The search strategy was presented as
follows:
#1 Stomach Neoplasm
#2 Gastric Neoplasm
#3 Stomach Cancer
#4 Gastric Cancer
#5 Stomach Neoplasm
#6 "Stomach Neoplasms" [Mesh]
#7 #1 OR #2 OR #3 OR #4 OR #5 OR #6
#8 Aidi zhusheye
#9 Aidi injection
#10 Aidi
#11 #8 OR #9 OR #10
#12 Random*
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#13 #7 AND #11 AND #12
Selection
Based on the inclusion and exclusion criteria, all
searched records were classified and sorted by reference
management software Endnote X6 (Thomson Reuters,
New York, NY, USA), with duplicated studies discard-
ed. Then, all abstracts were read and potentially eligi-
ble articles and citations for which a determination
could not be made were gathered. The full-text ver-
sions of these articles were then obtained to determine
eligibility. We contacted authors whose study reports
were incomplete or lacked relevant information.
Data extraction and quality assessment
Astandardized data extraction form was designed that
included basic information, the characteristics of in-
cluded studies, interventions, outcome measures, and
other information (Table 1).
Combined with the characteristics of TCM injection,
the risk of bias tool described in the Cochrane Hand-
book version 5.1.0
11
and methodological section of
CONSORT statement
12
were used to assess the quality
of each trial (Table 1). Each item was assessed as fol-
lowing two responses: "complete reporting" (low risk)
scored 1, while "No" or "Unclear" (high risk) scored.
The total scores were 8.
Statistical analysis
Assessment of heterogeneity: we used the Chi-squared
(χ
2
test to assess heterogeneity between trials and the I
2
statistic to evaluate the extent of inconsistency. If I
2
was less than 50%, and the P-value was greater than
0.05, then there was no statistical heterogeneity and
the fixed effects model was chosen for Meta-analysis,
otherwise the random effects model was used.
Data synthesis: dichotomous data were presented as an
odds ratio (OR), and continuous outcomes by mean
Item
Basic information
Characteristics
Interventions
Outcome measures
Quality assessment
Publication year
Source
Language of publication
First author
Sample size
Sex
Age
Pathological types of carcinoma
Cell types of carcinoma
Foundation item
Clinical stages
Interventions
Dosage
Chemotherapies
Treatment cycle
Efficience
Security
Other
Assessment of quality of life
Randomization
Randomization method
Blinding
Withdrawals/drop outs
Eligibility criteria for participants
Adverse events
Statistical methods
Interpretation
Year of publication of included RCT
Journal or degree paper
Chinese or English
Name of first author
Number of sample of included studies
Male or women
Range/average/medium of included participants
Early, advanced, or late GC
Adenocarcinoma, squamous carcinoma, SRCC, etc.
Number and nature on foundation
Ⅱ, Ⅲ
a
, Ⅲ
b
, Ⅲ
c
, Ⅳ
Aidi injection combine with types of chemotherapy
Dosage of Aidi injection
Name and composition of chemotherapies
Cycle of participants intervened
Name and number of efficience measures
Name and number of security measures
Name and number of other measures
KPS or others
Was the trial randomized?
What method was used to randomize?
Whether the blinding was described and performed
correctly?
As reported
As reported
Kinds of adverse events
Whether statistical methods were described?
Table 1 Data extraction items of included studies
Notes: RCT: randomized controlled trial; GC: gastric cancer; KPS: Karnofsky performance score.
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difference (MD), with 95% confidence interval (CI).
Forest plots were constructed to graphically present the
result of outcome measures. The differences in the effi-
cacy between interventions were considered statistically
significant if P ≤ 0.05.
Publication bias: a funnel graph was created to investi-
gate the likelihood of overt publication bias. All calcula-
tions were performedusing RevMan software (version
5.2, RevMan software, London, England).
13
RESULTS
Literature search
After the initial search, 124 potentially relevant publi-
cations were identified. All records were imported into
EndNote X6 and 54 trials were excluded because of du-
plication. Among the remaining 70 trials, 38 were ex-
cluded because they were animal studies, review arti-
cles, letters, or abstracts. Finally, 32 studies were evalu-
ated in our analysis
14-41,43-46
(Figure 1).
Characteristics of included trials
All 32 included studies were randomized, although no
detailed descriptions were provided. Each study fea-
tured Aidi injection combined with chemotherapy as
an intervention versus chemotherapy alone. Chemo-
therapy drugs included fluorouracil, mitomycin, oxali-
platin, cisplatin, paclitaxel, docetaxel, capecitabine, leu-
covorin, epirubicin, and mitomycin. A total of 1927
participants were included in the 32 studies. The medi-
an age of included participants was 60 (range: 31-108)
years. All participants were confirmed to suffer from
GC by pathology, computed tomography, cytology,
and gastroscopy. Nineteen studies reported clinical
stages, and most participants were in stages Ⅲ or Ⅳ.
A clinical efficacy rate was reported in 28 studies; 20
studies reported quality of life, and 20 studies used
Karnofsky performance status (KPS); 30 studies re-
ported adverse events including nausea and vomiting,
phlebitis, alopecia, bone marrow suppression, leuko-
penia, thrombocytopenia, and liver or kidney func-
tion damage. Six studies reported immune function
(Table 2).
Quality assessment
Table 3 shows the result of quality assessment. Only
two studies were found to be high quality (Score ≥ 6).
The percentage that reported randomization, methods
of randomization, blinding, description of blinding,
withdrawals and drop outs, eligibility criteria of partici-
pants, adverse events, and statistical methods were
96.88%, 6.25%, 0%, 0%, 96.88%, 100%, 93.75%,
and 93.75%, respectively.
Meta analysis results
Effective rate: twenty-eight studies
14,16,17,19-35,37-39,43-46
re-
ported effective rate. There was no heterogeneity across
the trials (P = 1.00, I
2
= 0%).Therefore, the fixed-effect
model was used to pool data. There was a statistically
significant difference between the injection combined
with chemotherapy group and the chemotherapy alone
group (OR = 1.52, 95% CI: 1.24, 1.86, P < 0.0001),
favoring the injection combined with chemotherapy
group (Figure 2).
Clinical beneficial rate
Twenty-four studies
14,16,17,19-21,24-35,37-39,44-46
reported the
clinical beneficial rate. There was no heterogeneity
across the trials (P = 1.00, I
2
= 0% ).Therefore, the
fixed-effects model was used to pool data.There was a
statistically significant difference between the injection
combined with chemotherapy group and the chemo-
therapy alone group [OR = 1.77, 95% CI: (1.33,
2.36), P < 0.0001], indicating the clinical beneficial
rate of injection combined with chemotherapy was bet-
ter than that of the chemotherapy alone (Figure 3).
Survival rate
One-year survival rateswere reported in six studies,
15,23,24,
29,44,45
and two studies
15,45
recorded 2-year survival rates.
No statistically significant heterogeneity was found
(P = 0.99, I
2
=0%), so we used the fixed-effects model
to pool data. There was no statistically significant dif-
ference between the two groups in 1-year survival rate
[OR = 1.51, 95% CI: (0.98, 2.34), P = 0.06] or 2-year
survival rate [(OR = 1.57, 95% CI: (0.61, 4.00), P =
0.35)] (Figure 4).
Quality of life
Twenty studies
17,19-21,23,24,26,27,29-31,33-36,39,41,43-45
used KPS to
evaluate quality of life. There was no heterogeneity
across the trials (P = 0.79, I
2
= 0%), so the fixed-effects
model was used to pool data. Compared with chemo-
Potential studies evaluating aidi injection for GC (n = 124)
EndNote find duplicates (n = 54)
Records screened (n = 70)
Screening abstract and title excluded:
Duplications (n = 24);
Not GC (n = 2);
Not chemotherapy (n = 1);
Review (n = 1);
Animal studies (n = 4).
Eligible for full text evaluation (n = 38)
Screening full text excluded:
Duplications (n = 2);
Not GC (n = 2);
Review (n = 1); Not aidi (n = 1).
32 trials for final meta analysis
Figure 1 Flow chart of article screening and selection pro-
cess
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Study
Ge YL
et al 2010
14
Liu HZ et al 2012
15
Zhang XD et al 2011
16
Tang YH et al 2007
17
Zhan J et al 2013
18
Ke YF et al 2010
19
Ding Z et al 2009
20
Tian X et al 2004
21
Wang ZL et al 2009
22
Gong NY et al 2006
23
Zhang ML et al 2009
24
Qin XY et al 2008
25
Miao YQ et al 2011
26
Chen NJ et al 2008
27
Lin H et al 2011
28
Fan CM et al 2011
29
Liu LH et al 2009
30
Chen LP et al 2012
31
Zeng QB et al 2006
32
Huo CS et al 2012
33
Zhao JG et al 2009
34
Chen YD et al 2012
35
Yang SM et al 2006
36
Yan HX et al 2012
37
Jia LQ et al 2003
38
Sample
A+C
25
28
16
34
25
23
38
23
30
26
53
30
41
36
22
23
30
25
23
32
32
29
54
32
23
C
25
28
15
30
25
22
37
22
26
30
51
30
43
34
24
28
30
25
22
33
30
28
54
34
22
Sex (man/women)
A+C
28/22
18/10
7/9
34/30
34/16
24/21
23/15
16/7
19/11
15/11
39/14
42/18
65/19
38/32
26/20
15/8
16/14
29/21
30/15
43/22
29/33
20/9
41/13
57/9
30/15
19/9
43/11
C
20/8
7/8
21/16
14/8
17/9
30/16
34/17
18/10
18/12
Age
A+C
NR
42-75/M56
52-73/M56
32-75/M58
35-75
28-75/M49
41-80
A52.4
35-78/A55
38-71/A54.2
61-79/M58
38-71/M60
M62
40-68/A56.7
32-75/M56
37-83/M56.7
M50.6
54-75/M62
M52.4
36-71/A48.5
28-75/M49
43-69/M56
43-75/A56.3
42-75/A61.7
32-70/A56.8
C
35-76/M58
49-
75/M58
39-79
A53.1
35-85/A57
41-69/A55.4
60-85/M71
39-78/M57.8
M49.6
42-68/M55
42-76/A55.6
Intervention
A+C
AIDI+MF/CF
AIDI+SO
X
AIDI+XELOX
AIDI+DCF
AIDI+XELOX
AIDI+XELOX
AIDI+HELF
AIDI+FP
AIDI+FAM
AIDI+TPLF
AIDI+FP
AIDI+ECF
AIDI+FOLFOX4
AIDI+FOLFOX4
AIDI+POF
AIDI+L-OHP
AIDI+TPF
AIDI+EOF
AIDI+OFL
AIDI+OFL
AIDI+TX
AIDI+FOLFOX
AIDI+FAD
AIDI+FOLFOX4
AIDI+FD
C
MF/CF
SOX
XELOX
DCF
XELOX
XELOX
HELF
FP
FAM
TCF
FP
ECF
FOLFOX4
FOLFOX4
POF
L-OHP
TPF
EOF
OFL
OFL
TX
FOLFOX
FAD
FOLFOX4
FD
Dosages/
mL
50
60
50
60
50-100
50-100
100
50
50
50
50
50
50-80
50
100
50
50
50
50
50
80
80
50-100
100
50
Outcome
①②
①②
①②③④
①⑤
①②
①②⑤
①②⑤
①②⑤
①②③⑤
①②⑤
①②③⑤
①②
①②⑤
①②
①②
①②③⑤
①②⑤
①②⑤
①②④
①②⑤
①②⑤
①②⑤
①②
①②④
①②④
KPS
NR
NR
NR
＞70
NR
≥70
≥60
>50
NR
≥60
≥60
NR
＞60
＞70
NR
≥60
≥60
≥60
NR
NR
≥60
50-80
NR
＞70
NR
Duration
2
4
2
＞2
NR
＞2
6
2
3
4
2
2
≥2
3
＞2
≥4
≥2
≥2
≥2
2
≥2
2
3-4
1
2
Table 2 Basic characteristics of included 32 studies
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therapy alone, the injection combined with chemother-
apy significantly improved the quality of life for pa-
tients [OR = 3.02, 95% CI: (2.39, 3.82), P < 0.000
01] (Figure 5).
Adverse events
Compared with the group using chemotherapy alone,
the injection combined with chemotherapy could re-
duce the incidence of the following adverse events: nau-
sea and vomiting
15,19,23-26,29-31,33,34,36,43
[OR = 0.34, 95% CI:
(0.24, 0.47), I
2
= 0%, P < 0.000 01], diarrhea
15,19,21,23,24,29,
32,34,38,43,44
[OR = 0.47, 95% CI: (0.33, 0.69), I
2
= 0%,
P < 0.00001] (Figure 6), leukopenia (Ⅲ-Ⅳ)
17,19,20,23-31,34,
36,37,43
[OR = 0.34, 95% CI: (0.23, 0.51), I
2
= 0%, P =
0.05], hemoglobin decrease (Ⅲ-Ⅳ)
23,29,34,37
[OR = 0.42,
95% CI: (0.18, 1.00), I
2
= 0%, P = 0.05], thrombocy-
topenia ( Ⅲ-Ⅳ)
19,20,23-25,27-31,34,36
[OR = 0.46, 95% CI:
(0.22, 0.96, I
2
= 0%, P = 0.04] (Figure 7), damage to
liver function
15,17,23-26,28-31,34
[OR = 0.36, 95% CI: (0.24,
0.54, I
2
= 22%, P < 0.000 01], and damage to kidney
function
17,23-25,30,31,34
[OR = 0.74, 95% CI: (0.35-1.58),
I
2
= 0%, P = 0.448] (Figure 8).
Immune function
Six studies
17,21,23,32,37,39
reported indexes related to im-
mune function, but one study
32
was excluded because
SD valueswere not reported. There was high statistical
heterogeneity across the studies (P < 0.000 01, I
2
=
95%), so the random-effects model was used to pool
data. The injection combined with chemotherapy sig-
nificantly improved CD3, CD4, CD4/CD8, and NK
cells levels
for patients: CD3 [MD = 6.50, 95% CI:
(1.31, 11.69), P = 0.01], CD4 [MD = 6.63, 95% CI:
(4.35, 8.92), P < 0.000 01], CD4/CD8 [MD=0.56,
95% CI: (0.36, 0.77), P < 0.000 01], and NK [MD=
5.23, 95% CI: (1.43, 9.04), P = 0.007] (Figure 9).
Publication bias
A funnel graph on effective rate was plotted to investi-
gate the likelihood of overt publication bias. The fun-
nel plot was not symmetrical, indicating the likelihood
of publication bias (Figure 10).
DISCUSSION
Aidi injection was shown to have curative effects for liv-
er cancer and lung cancer.However, a greater number
of large-scale, double-blind, randomized control trials
is needed for the patients of GC.
42
A previous Me-
ta-analysis for Aidi injection combined with chemo-
therapy included 15 RCTs.
42
The study found that
Aidi injection was beneficial in GC treatment. Howev-
er, this previous study was limited because of the quali-
ty of the included RCTs, the low number of included
studies, and publication bias.
This Meta-analysis included 32 RCTs to systematical-
ly and comprehensively examine the effectiveness,
safety, and immune function of Aidi injection com-
Notes: A+C: Aidi injection+chemotherapy; C: chemotherapy; A: average; M: median; NR: not reported; MF/CF: fluorouracil/mitomycin; SOX: oxaliplatin+tegafur; XELOX: oxaliplatin+capecitabine; DCF:
docetaxel+cisplatin; HELF: fluorouracil+leucovorin calcium+etoposide + HCPT; TP: fluorouracil+cisplatin; FAM: fluorouracil+mitomycin+adriamycin; ECF: adriamycin+cisplatin+fluorouracil; FOLFOX: ox-
aliplatin+fluorouracil+leucovorin calcium; POF: paclitaxel+leucovorin calcium+fluorouracil+oxaliplatin; TPF: paclitaxel+cisplatin+fluorouracil; EOF: epirubicin+fluorouracil+oxaliplatin; OFL: fluorouracil+ox-
aliplatin+mitomycin; TX: paclitaxel+capecitabine; FD: fluorouracil+cisplatin; TG: tegafur+gimeracil; KPS: Karnofsky performance score.
Study
Han WL
et al 2011
39
Zhu XQ et al 2009
40
Zhang AX et al 2009
41
Han SR et al 2009
43
Wen X et al 2010
44
Wang YL et al 2007
45
Ruan FX et al 2012
46
Sample
A+C
31
34
35
24
27
32
32
C
30
33
32
23
29
32
32
Sex (man/women)
A+C
20/11
20/14
20/15
13/11
46/10
44/20
19/13
19/11
21/12
19/13
12/11
17/15
C
Age
A+C
45-70/A67.3
37-73/M60
30-71/A55
38-71/A54.2
47-78/A60.3
32-74/M48
56-84/A67.6
C
45-70/A66.1
39-74/M58
32-68/A53
41-69/A55.4
58-83/A68.4
Interventions
A+C
AIDI+TG
AIDI+FOLFOX4
AIDI+FOLFOX4
AIDI+TCF
AIDI+DFC
AIDI+XELOX
AIDI+Capecitabine
C
TG
FOLFOX4
FOLFOX4
TCF
DFC
XELOX
Capecitabine
Dosage/
mL
80
100
50
80-100
80
60
60
Outcome
①④⑤
⑤
①②
①②⑤
①②⑤
①②⑤
①②
KPS
＞60
＞60
NR
＞60
≥60
≥70
NR
Durations
≥2
≥2
3
1
≥2
6
1
Table 2 Basic characteristics of included 32 studies (continuted)
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Table 3 Results of quality assessment
Study
Ge YL
et al 2010
14
Liu HZ et al 2012
15
Zhang XD et al 2011
16
Tang YH et al 2007
17
Zhan J et al 2013
18
Ke YF et al 2010
19
Ding Z et al 2009
20
Tian X et al 2004
21
Wang ZL et al 2009
22
Gong NY et al 2006
23
Zhang ML et al 2009
24
Qin XY et al 2008
25
Miao YQ et al 2011
26
Chen NJ et al 2008
27
Lin H et al 2011
28
Fan CM et al 2011
29
Liu LH et al 2009
30
Chen LP et al 2012
31
Zeng QB et al 2006
32
Huo CS et al 2012
33
Zhao JG et al 2009
34
Chen YD et al 2012
35
Yang SM et al 2006
36
Yan HX et al 2012
37
Jia LQ et al 2003
38
Han WL et al 2011
39
Zhu XQ et al 2009
40
Zhang AX et al 2009
41
Han SR et al 2009
43
Wen X et al 2010
44
Wang YL et al 2007
45
Ruan FX et al 2012
46
Randomization
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Randomization method
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
1
1
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Blinding
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Blinding method
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
Withdrawal/
drop out
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Eligibility criteria
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
Adverse event
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
1
Statistical method
1
1
1
1
0
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
0
1
1
1
1
Overall score
5
5
5
5
3
5
5
5
5
5
4
5
5
5
5
6
6
5
5
5
5
5
5
5
5
5
4
4
5
5
5
5
367
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Figure 2 Effective rate Meta-analysis
Figure 3 Clinical beneficial rate Meta-analysis
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bined with chemotherapy versus chemotherapy alone
for GC. We found that Aidi injection combined
with chemotherapy significantly improved effective
rate, clinical beneficial rate, quality of life, immune
function, and reduced some adverse events (nausea
and vomiting, diarrhea, leukopenia (Ⅲ-Ⅳ), hemoglo-
bin levels ( Ⅲ-Ⅳ), thrombocytopenia ( Ⅲ-Ⅳ), and
damage to liver and kidney function). The injection
combined with chemotherapy showed a trend to-
wards increasing survival rate, but there was no sig-
nificant difference between the two groups.
All included RCTs were randomized, but most of the
32 studies (90.63%) failed to describe the randomiza-
tion methods. A statement such as "we randomly allo-
cated" or "use a randomized design" was insufficient to
confirm that the allocation sequence was genuinely ran-
domized. One study,
17
which used paired admission
number, is considered to have high risk of bias. One
studyused a table of random numbers
29
and another
drew lots
30
to generate randomized sequences, which
areboth considered to have a low risk of bias. None of
the studies reported whether there was blinding. This
Figure 4 Survival rate Meta-analysis
Figure 5 Quality of life Meta-analysis
369
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Wang JC et al. / Systematic Review
result could lead to implementation and measurement
bias. Overall, the risk of bias in the included 32 stud-
ies was found to be medium. The funnel graph indi-
cated a high likelihood of publication bias, which
meansthat negative resultsare less likely to be pub-
lished.
All studies included in our Meta-analysis were pub-
lished in Chinese. We used a comprehensive search
strategy and strived to reduce selection bias by
searching PubMed, EMBASE, Cochrane Library, Sci-
ence Citation Index Expanded, and the Chinese-for-
eign Conference Database. However, no studies pub-
lished in English were found. Although we included
32 studies covering 1927 participants, only two stud-
ies included samples of more than 100 patients.
More large-scale randomized double-blind control tri-
als are needed to overcome methodological and re-
porting flaws.
There are some critical reporting flaws ofthe included
studies.The methods of randomization were not de-
scribed, and blinding was not reported. Therefore, the
authenticity and reliability of the results of all included
studies are affected.
Compared with chemotherapy alone, Aidi injection
combined with chemotherapy could improve the effec-
tive rate; clinical beneficial rate; quality of life; im-
mune function; and reducethe incidence of nausea and
vomiting, diarrhea, leukopenia ( Ⅲ-Ⅳ), hemoglobin
decreases (Ⅲ-Ⅳ), thrombocytopenia (Ⅲ-Ⅳ), damage
to the liver and kidney. Use of the CONSORT state-
ment
47
for RCTs is recommended for stricter reporting
of detailed information.
Figure 6 Nausea, vomiting, and diarrhea Meta-analysis
370
Wang JC et al. / Systematic Review
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ACKNOWLEDGMENTS
Theoretical support was given by the Evidence Based
Medical Center of Lanzhou University. Sincere thanks
go to colleagues of Evidence Based Medical Center of
Lanzhou University for their help on this work.
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