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Efficacy and safety of gemcitabine-capecitabine
combination therapy for pancreatic cancer
A systematic review and meta-analysis of randomized controlled
trials
Guoqing Ouyang, MD, Yongrong Wu, MD, Zhen Liu, MD, Wuchang Lu, MD, Shuai Li, MD,
Shuqing Hao, MD, Guangdong Pan, MD
∗
Abstract
Background: Recent randomized controlled trials revealed the combination of gemcitabine and capecitabine (GemCap) regime
shows promising efficacy in pancreatic cancer patients. Here, we conducted a meta-analysis to compare the efficacy and safety of
gemcitabine (Gem) with GemCap for pancreatic cancer.
Methods: The database of MEDLINE (PubMed), EMBASE, Cochrane Central Controster of Controlled Trials, Web of Science was
searched for relevant randomized controlled trials before 8 April, 2020. The outcomes were overall survival (OS), 12-month survival
rate, progress free survival (PFS), partial response rate (PRR), objective response rate (ORR), and Grade 3/4 toxicities.
Results: Five randomized controlled trials involving 1879 patients were included in this study. The results showed that GemCap
significantly improves the OS (hazard ratio =1.15, 95% CI: 1.037-1.276, P=.008), PFS (hazard ratio =1.211, 95% CI 1.09-1.344,
P=0), PRR (relative risk (RR) =0.649, 95% CI 0.488-0.862, P=.003), ORR (RR =0.605, 95% CI 0.458-0.799, P=0), and the overall
toxicity (RR =0.708, 95% CI 0.620-0.808, P=.000) compared to Gem alone. However, no significant difference was found in 12-
month survival.
Conclusions: Despite a higher incidence of Grade 3/4 toxicity, GemCap was associated with better outcomes of OS, PFS, PRR,
ORR, as compared with Gem, which is likely to become a promising therapy for pancreatic cancer.
Abbreviations: 5-FU =5-fluorouracil, Gem =gemcitabine, GemCap =gemcitabine and capecitabine, HR =hazard ratio, ORR =
objective response rate, OS =overall survival, PFS =progress free survival, PRR =partial response rate, RCTs =recent randomized
controlled trials, RR =relative risk.
Keywords: capecitabine, gemcitabine, meta-analysis, pancreatic cancer
1. Introduction
Pancreatic cancer is the fourth leading cause of cancer-related
death in the world,
[1]
and the incidence of pancreatic cancer has
been increasing rapidly in recent years. Almost 96% of pancreatic
cancer was constituted with pancreatic ducal adenocarcinoma.
[2]
It is expected that pancreatic cancer will become the 2
nd
leading
cause of cancer-related death by 2030.
[3]
The prognosis of
pancreatic cancer was extremely poor with a 1-year survival rate
was around 18% and 5-year survival rate was less than 8%.
[4–6]
Surgical resection remains the only treatment that can achieve
long-term survival. Because the majority of patients are
diagnosed with local advanced or metastatic, only 15% to
20% of patients are amenable to surgical resection.
[7,8]
Therefore, chemotherapy becomes the first-line treatment for
advanced and metastatic pancreatic cancer.
Gemcitabine (Gem) was recommended as the gold
standard treatment for pancreatic cancer due to a Phase III
clinical trial that found Gem achieved a better survival rate and
more clinical benefits than 5-fluorouracil (5-FU). Gem has
acquired about a 20% increase in 1-year survival rate and
a median overall survival of 5 to 7 months in metastatic
pancreatic cancers.
[9]
However, the therapeutic effect of Gem
monopoly is still not satisfactory,
[9,10]
it calls for the need of
better treatment strategies for pancreatic cancer. To improve
clinical benefit of pancreatic cancer, various anti-tumor agents
combined with Gem were recently attempted in numerous
clinical setti ng, such as Nab-paclitaxel and FOL FIRINOX (5-FU,
Oxaliplatin, Irinotecan, folinic acid), cisplatin, oxaliplatin,
docetaxel et al, but most studies cannot show a significant
improvement in overall survival (OS) or a better tolerance of
Editor: Maya Saranathan.
This study was supported by the Hubei Chen Xiaoping Technology Development
Fund (CXPJJH1190000-2019321).
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are
publicly available.
Department of Hepatobiliary Surgery, Liuzhou People’s Hospital, Liuzhou,
Guangxi, China.
∗
Correspondence: Guangdong Pan, Department of Hepatobiliary Surgery,
Liuzhou People’s Hospital, Liuzhou, Guangxi 545006, China
(e-mail: pgdhx@126.com).
Copyright ©2021 the Author(s). Published by Wolters Kluwer Health, Inc.
This is an open access article distributed under the terms of the Creative
Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is
permissible to download, share, remix, transform, and buildup the work provided
it is properly cited. The work cannot be used commercially without permission
from the journal.
How to cite this article: Ouyang G, Wu Y, Liu Z, Lu W, Li S, Hao S, Pan G.
Efficacy and safety of gemcitabine-capecitabine combination therapy for
pancreatic cancer: a systematic review and meta-analysis of randomized
controlled trials. Medicine 2021;100:48(e27870).
Received: 28 March 2021 / Received in final form: 23 September 2021 /
Accepted: 3 November 2021
http://dx.doi.org/10.1097/MD.0000000000027870
Systematic Review and Meta-Analysis Medicine®
OPEN
1
toxicities than Gem monopoly, except for combing capecitabine
or erlotinib.
[11–14]
Capecitabine is a designed oral fluoropyrimidine carbamate
that is associated with a lower incidence of toxicities and achieved
similar efficacy compared with intravenous 5-FU.
[15]
The
convenience of oral administration makes capecitabine widely
used in various tumors. Capecitabine is currently approved by the
FDA for the treatment of breast cancer and colorectal cancer.
[16]
Capecitabine monopoly has been found to be safe and effective in
advanced pancreatic cancer in a phase II study and demonstrated
similar benefits in tumor-related symptoms with Gem.
[9,17]
Though capecitabine led to a modest clinical benefit, it failed
to improve the terrible prognosis. To obtain better clinical
benefits, various capecitabine-based schemes have been
attempted in multiple clinical research.
Gemcitabine and capecitabine (GemCap) are both nucleoside
analogs and the combination show synergism to antitumor.
Furthermore, both drugs have nonoverlapped toxicity and are
well tolerated.
[16,18,19]
Previous studies have shown Gem
combined capecitabine improved overall survival rate, progres-
sion-free survival (PFS) and achieved a better tumor response
than Gem alone.
[11,16,19–21]
However, some clinical benefit in the
5 studies are quite contrary. In this study, we conducted this
systematic review and meta-analysis of the currently available
randomized controlled studies to evaluate the efficacy and safety
of the gemcitabine-capecitabine (Gem-Cap) and Gem alone for
the patients of pancreatic cancer.
2. Methods
2.1. Search strategy
From inception to 8 April, 2020, comprehensive electronic
searches were performed with the database of MEDLINE
(PubMed), EMBASE, Cochrane Central Register of Controlled
Trials, Web of Science. The search terms and strategy are based
on the combination of the following keyword: (“pancreatic
cancer”) AND (“gemcitabine”or “Gemzar”) AND (“capecita-
bine”or “Xeloda”) AND (“randomized controlled trial”). The
searching language was restricted to English. This meta-analysis
was conducted following the guidelines provided by the PRISMA
statement.
2.2. Inclusion and exclusion criteria
Trials, were included in this meta-analysis should fulfill the
following criteria: The study was randomized controlled trials
(RCTs; Phase II or III) with Gem and GemCap treatment.
Cytologically or histologically ascertained pancreatic cancer; Age
was between 18 and 85years; Karnofsky performance status
score ≥50% (or WHO Health Organization performance status
2), adequate bone marrow, hepatic, and renal functions; No
previous chemotherapy or radiotherapy.
The exclusions are as follows: Studies were not RCTs such as
reviews and case reports, full text unavailable and non-published
conference was also excluded. For Duplicate publications, the
most comprehensive article was selected. Single-arm studies.
2.3. Data extraction
The data extracted and quality assessment was performed
independently by 2 authors (i.e., GQOY and WC L). Any
disagreement between 2 authors was resolved after discussing
with a third reviewer (YRW) and a consensus was achieved. The
following data were extracted: The first author’s name, year of
publication, gender distribution, study design, treatment group,
number of patients, patient characteristics. The outcome of
treatment, such as CRR, objective response rate (ORR), partial
response rate (PRR), OS, PFS, toxicities. If the same trail reported
in different publications, the most recent publication or
comprehensive one was chosen. If log hazard ratio (HR) and
its variance of overall survival or forgeprogression-free survival
was not provided directly in the text but only in figures, Engauge
Digitizer version 4.1 (http://digitizer.sourceforge.net/) was used
to read the Kaplan-Meier curves.
2.4. Quality assessment
The Jadad score was used to assess the quality of the included
RCTs. The 3 items of Jadad are as follows: randomization,
double blinding, withdrew wals and dropouts. Jadad score
ranged from 0 to 5, and ≥3 was considered high-quality
literature.
[22]
2.5. Statistical analysis
All analyses were performed with Stata version 12.0 software
(Stata Corporation, College Station, TX) according to the
Cochrane Handbook for Systematic Review. The primary
endpoint of this meta-analysis was included OS and PFS. OS
was defined as the time between date of random assignment and
the date of death from any cause. PFS was defined as the time by
random assignment to disease progression. The second endpoints
included 12months survival rate, ORR, PRR, CRR, Grade 3-4
toxicities. The HRs with 95% CIs were used to express the results
of OS and PFS. The pooled odds ratio with 95% CI was
calculated for the second point. The x
2
-based Q-test and I
2
statistics were used to assess the heterogeneity. If there were
statistical differences in terms of heterogeneity (I
2
>50%,
P<.10), a random effects model was used
[23]
; otherwise, a fixed
effects model was selected. A Pvalue less than .05 was considered
statistically significant. The possibility of publication bias was
ascertained by visually funnels plots.
2.6. Ethical statement
The data analyzed in this study was extracted from previously
published studies, and therefore ethical approval was not
necessary.
3. Results
3.1. Literature search
After searching literature within several databases, a total of
1382 potentially relevant studies was eventually identified for
screening (Fig. 1). After duplicating and screening the titles and
abstracts, 15 studies were enrolled for full-text screening. Of the
15 remaining studies, 8 were excluded because they were non-
randomize trials and 2 were excluded because they were single-
arm control study. Finally, 5 RCTs compared Gem alone with
GemCap in pancreatic cancer were included in this meta-
analysis.
[11,16,19–21]
Ouyang et al. Medicine (2021) 100:48 Medicine
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3.2. Study characteristics
The baseline characteristic of the enrolled studies is summarized
in Table 1. Five studies including a total of 1879 patients with
pancreatic cancer were included in the final analysis, 939 patients
were assigned to the Gem group and 940 to the GemCap group.
All included trials were considered high qualities, with a score of
3 in Jadad score. Of the 5 trials, 4 were randomized phase II trials
and 1 were phase II trial. The patient of these trials came from the
UK, Germany, France, Sweden, Austria, Italy, Switzerland, and
South Korea. Four studies were done in Europe and 1 in Asia. The
Table 1
Characteristics of 5 included trials in the meta-analysis.
Male/female Median age (range)
Studies Year Publication type Inclusion period Total number Gem GemCap Gem GemCap Jadad score
Scheithauer W 2003 Phase 2 1996.6-2001.5 83 23/19 27/14 66 (39-75) 66 (40-75) 3
Herrmann R 2007 Phase 3 2001.6-2004.6 319 85/74 86/74 NA NA 3
Cunningham D 2009 Phase 3 2002.2-2005.1 533 153/113 160/167 62 (26-83) 62 (37-82) 3
Lee HS 2017 Phase 3 NA 214 57/49 63/45 64 (43-85) 64 (37-80) 3
Neoptolemos JP 2017 Phase 3 2008.11-2014.9 730 212/154 202/162 65 (37-80) 65 (39-81) 3
Gem =gemcitabine, GemCap=gemcitabine plus capecitabine, NA=not available.
Figure 1. Flow diagram for identifying and including studies in the meta-analysis.
Ouyang et al. Medicine (2021) 100:48 www.md-journal.com
3
period of publication ranged from 2003 to 2017. The ratio of
male/female in the Gem group was 530/409 and in GemCap
group was 538/402.
3.3. Twelve-month survival rate and overall survival
The 12-month survival data were reported for 4 trials. A total of
1665 pancreatic cancer patients from these 4 trials, 833 from the
Figure 2. A: Twelve-month survival rate results are not associated with the Gem group and the GemCap group. B: Meta-analysis of OS results for the Gem group
and the GemCap group. CI=confidence interval, Gem =gemcitabine, GemCap =gemcitabine and capecitabine, HR =hazard ratio, RR =relative risk.
Ouyang et al. Medicine (2021) 100:48 Medicine
4
Gem group and 832 from the GemCap group, was enrolled in our
meta-analysis. The consequences of this meta-analysis shows that
no statistically significant difference was found in the 12-month
survival rate between 2 groups (relative risk (RR) =0.958, 95%
CI 0.886-1.035, P=.278) (Fig. 2A). And no inter-group
significant heterogeneity was detected in the 12-months survival
rate (I
2
=0, P=.88).
HR and its 95% CI for OS was available in all included
studies. After performing a meta-analysis, the pooled HR
between the Gem group and the GemCap group was 1.15
(95% CI: 1.037-1.276, P=.008) (Fig. 2B). The result revealed
that Gem group was associated with a statistically significant
19% increase in HR for OS than the GemCap group. There
was no significant heterogeneity has observed in the OS (I
2
=
0, P=.998,), so a fixed-effects model was employed to pool
the data.
3.4. Progression-free survival
The relevant PFS data were reported for 4 trials. A total of 1073
patients from these 4 studies, 537 from the Gem alone group and
576 from the GemCap group, was enrolled in this meta-analysis.
After pooling the data, no heterogeneity among the studies was
detected (I
2
=0, P=.86); therefore, a fixed-effects model was
used. There was a significant difference exist between Gem-alone
groups and GemCap groups. The overall meta-analysis revealed
that Gem increase 21.1% of HR for PFS (HR =1.211, 95% CI
1.09-1.344, P=.860) (Fig. 3).
3.5. Partial response rate and objective response rate
In this meta-analysis, both PRR and ORR were analyzed,
whereas CRR was not analyzed because of data deficient. Four
studies involving a total of 1133 patients compared the PRR and
ORR between the Gem alone group and the GemCap group.
After pooling the data, the results revealed that GemCap group
significantly improved the PRR than in the Gem-alone group (RR
=0.649, 95% CI 0.488-0.862, P=.003) (Fig. 4A), and there was
no heterogeneity was detected regarding the outcome of PRR (I
2
=16.3%, P=.31), a fixed-effects model was employed. The
combined group of GemCap was associated with higher ORR
than Gem monopoly (RR =0.605, 95% CI 0.458-0.799, P=0),
and fixed-effects model was used because no heterogeneity was
found (I
2
=0, P=.44) (Fig. 4B).
3.6. Toxicity
Five trials reported the incidence of Grade 3/4 neutropenia,
anemia, and diarrhea
[11,16,19–21]
; 4 trials reported the incidence of
Grade 3/4 thrombocytopenia and stomatitis.
[11,16,20,21]
Three
trials reported the incidence of Grade 3/4 Nausea
[11,16,21]
and
febrile neutropenia.
[16,20,21]
The Grade 3/4 toxic effects were calculated with dichotomous
data (RR, 95% CI) and the results of 2 arms were summarized
in Table 2. As shown in Table 2, the most common toxicity of
2 arms was neutropenia (25.8%), and the incidence of the
remaining toxicity was all below 7%. After pooling the data,
there was no heterogeneity was found except for thrombocyto-
Figure 3. Meta-analysis of PFS results for the Gem group and the GemCap group. CI =confidence interval, Gem =gemcitabine, GemCap =gemcitabine and
capecitabine, HR =hazard ratio, PFS =progress free survival.
Ouyang et al. Medicine (2021) 100:48 www.md-journal.com
5
penia while the I
2
was 62.6% (Table 2). Therefore, thrombocy-
topenia used a random effect model and the other 6 toxic events
used the fixed-effects model. The pooled results show that as
compared with Gem alone, GemCap group significantly
increased the incidence of neutropenia, diarrhea; whereas no
significant difference was found in the incidence of anemia,
neubrimbocytopenia, febrile neutropenia, nausea, diarrhea
between 2 groups (as shown in Table 2). The results of
this meta-analysis based on the merging of the 7 toxic events
revealed that Gem alone associate with lower toxicity than the
GemCap group (RR =0.708, 95% CI 0.620-0.808, P=.000)
(Fig. 5).
Figure 4. A: Meta-analysis of PRR results for the Gem group and the GemCap group. B: Meta-analysis of ORR results for the Gem group and the GemCap group.
CI =confidence interval, Gem =gemcitabine, GemCap =gemcitabine and capecitabine, ORR =objective response rate, PRR =partial response rate, RR =
relative risk.
Ouyang et al. Medicine (2021) 100:48 Medicine
6
3.7. Publication bias
Begg funnel plot and Egger test were used to evaluating the
potential publication bias of the included studies. The result
indicated that there was no obvious publication bias for OS,
analysis (Bgger test: P=.806 for OS) (Fig. 6A). The Egger test did
not demonstrate any publication bias (P=.373 for OS) (Fig. 6B).
4. Discussion
Pancreatic cancer is one of the most fatal malignant neoplasms
with an overall 5-year survival rate for all stages is no more than
8% and the ratio of mortality/incidence is 98%.
[6,24]
Although
surgical resection is the only way to provide curative treatment,
more than 80% of patients with pancreatic cancer are ineligible
to be resected at diagnosed, because they usually metastasize to
the distant organ or invading the major vessel when diag-
nosed.
[25]
Therefore, chemotherapy has become an alternative
choice for pancreatic cancer patients. Since 1997, Gem has
become the mainstay for the treatment of pancreatic cancer.
[9]
After that, Gem has become cornerstone treatment for patients
with pancreatic cancer. In recent years, many randomized
controlled trials have aimed at assessing the potential benefits of
Gem-based combination over Gem monopoly. According to
meta-analysis, Gem-based combination chemotherapy signifi-
cantly improved the OS, ORR, and PFS in advancer pancreatic
cancer patients. However, the combined group was associated
with increased toxicity.
[26]
Capecitabine is widely used in many
solid malignancies, particularly in gastrointestinal and breast
Figure 5. Meta-analysis of toxicity results in the Gem group and the GemCap group. CI =confidence interval, Gem =gemcitabine, GemCap =gemcitabine and
capecitabine, RR =relative risk.
Table 2
Toxicities of Gem and GemCap.
Toxicity Gem
n/N
GemCap
n/N
RR 95% CI I
2
P
Neutropenia 188/909 282/912 0.667 0.569-0.781 0 .818
Anemia 42/909 36/912 1.174 0.762-1.809 0 .481
Thrombocytopenia 32/543 38/553 1.083 0.396-2.961 62.6% .046
Febrile neutropenia 4/296 7/302 0.614 0.197-1.913 0 .693
Diarrheas 20/909 43/912 0.479 0.288-0.799 6.5% .370
Nausea 22/442 25/450 0.895 0.513-1.561 0 .993
Stomatitis 3/543 11/553 0.367 0.126-1.071 0 .506
CI =confidence interval, Gem =gemcitabine, GemCap=gemcitabine plus capecitabine, RR=relative ratios.
Ouyang et al. Medicine (2021) 100:48 www.md-journal.com
7
tumors, but also in pancreatic cancer.
[27]
The question of whether
GemCap can achieve a better benefit than Gem alone is still
unclear.
We performed the present meta-analysis to compare the
efficacy and tolerability of GemCap vs Gem alone for pancreatic
cancer patients. Five randomized trials include a total of 1879
patients enrolled into this study. Our pooled analysis revealed
that Gem alone may lower the RR for 12-month survival rate
than GemCap; however, no significant difference was found and
heterogeneity was detected (I
2
=0, P=.88). It was indicated that
the combination group could not prolong the 12-months survival
rate. The pooled HR for OS in our analysis was 1.19, indicating a
19% decline in the risk of death in pancreatic cancer patients
treated with GemCap regimen. The median OS reported by the
included 5 studies varied from 6.2 to 25.5 months in Gem group
and from 7.1 to 28.0 months in GemCap regimen. However,
Neoptolemos JP
[19]
reported the median OS in Gem and GemCap
was 25.5 months and 28.0 months which was higher than the rest
of the 4 studies. The difference between the included articles was
due to the fact that the patients included in Neoptolemos JP
[19]
research were undergo surgical resection, while the enrolled
patients of other studies were metastatic or advanced pancreatic
cancer. As a result, we performed a subgroup analysis based on
whether conducted resection and find that resection did not affect
the result of OS between Gem and GemCap group (HR 1.15,
P=.008). The median PFS in Gem alone group ranged from 3.8
to 5.3 months and 4.3 to 6.2 months in the GemCap group. The
result shows that GemCap significantly reduces the hazard of
death by 21.1% compared to Gem alone. Our results were also
consistent with those of Cunningham D’s study.
[11]
A meta-
analysis
[28]
that reported Gem-based combination therapy could
improve the OS and PFS, but not the 12-months survival rate was
similar to our study. Based on the above results, though GemCap
might not achieve a better outcome in 12-months survival rate,
the OS and PFS were superior in GemCap compared to Gem
alone. Thus, Gem plus capecitabine is more recommended over
Gem monopoly.
The present meta-analysis showed that GemCap significantly
increases PRR and ORR by 35.1% and 39.5% as compared with
Gem monopoly. Our previous meta-analysis compared Gem plus
cisplatin vs Gem alone revealed that the combination regime
improves the outcome of ORR.
[29]
It was indicated that Gem
combines with capecitabine or cisplatin might achieve synergistic
effects. Another meta-analysis also suggested that Gem-based
combination therapy increased 58% of ORR than Gem
monotherapy, especially when combined with Gem or oxalipla-
tin; moreover, the combinations of Gem plus platinum
fluoropyrimidine improved ORR by 47% as compared with
Gem alone.
[30]
Capecitabine is an oral fluoropyrimidine seems to
be a substitute intravenous 5-Fu, with the advantage of no need
injection.
[27]
Lee et al
[20]
reported that GemCap significantly
improved ORR (43.7% vs 17.6%; P=.001), but fail to improve
OS (HR, 0.82; 95% CI, 0.67-1.01; P=.06) and PFS (HR, 0.87;
95% CI, 0.73-1.03; P=.08) compared with Gem monopoly.
Some of the above results are different from ours because we
found that GemCap not only improves not ORR but also
improves OS and PFS.
In the present study, we found that the GemCap was associated
with higher odds for Grade 3/4 toxic effects compared with Gem
alone. Pooled adverse data significantly increased by 29.2% in
GemCap over Gem alone (RR =0.708, 95% CI 0.620-0.808,
P=.000).
Previous studies proved that several new combination chemo-
therapies offer superior survival outcome and PFS than Gem
alone regimens; however, it could not apply to all pancreatic
cancer patients due to its severe toxicity.
[31–33]
The incidence rate
of toxicity was under 7% except for neutropenia (25.8%);
nevertheless, the incidence of neutropenia is still very low when
compared to Gem plus S-1(63.3%).
[34]
It is well known that if
patients experience serious adverse events during chemotherapy,
the physician may reduce the dosage or even stop the
chemotherapy, so lower toxicity effects were important for
pancreatic cancer patients to improve the tolerance of chemo-
therapy.
Our meta-analysis reveals a statistically significant greater
incidence of grades III/IV toxic effects in the GemCap regime, the
12-months survival, OS, PFS, PRR, and ORR, however,
significantly increased may make the adverse events generally
tolerable and reversible. However, due to the specific data that
could not be obtained, more studies are required to further verify
the greatest beneficiary from this treatment.
There are some limitations in the present meta-analysis and
there were: our study only enrolled 5 RCTs and the sample size of
each regimen relatively too small to provide sufficient evidence
for the safety and efficiency of pancreatic cancer between
GemCap and Gem alone. Therefore, more RCTs with larger
sample sizes are required. Our study was based on literature and
was associated with publication bias; the present meta-analysis
was an inference from published abstracted data rather than
individual patient profiles. Different dose and modification
Figure 6. A: Begg funnel plot of public ation bias test. B: Egger publication bias
plot. HR =hazard ratio.
Ouyang et al. Medicine (2021) 100:48 Medicine
8
schemes of Gem or capecitabine may generate divergent
outcomes. The status of pancreatic cancer in 4 included studies
was advanced or metastasis and only treated with chemotherapy,
however, the status in Neoptolemos JP
[19]
was resected
pancreatic cancer and patients were conducted surgical resection
before chemotherapy. We hope further RCTs may resolve the
above problems and provide much more high-quality clinical
evidence.
5. Conclusions
This meta-analysis of randomized control studies revealed that
GemCap significantly improves OS, PFS, PRR, ORR; however,
no significant difference was found in the 12-months survival
rate. Though the incidence of Grade 3/4 toxicity was higher in
GemCap compared with Gem alone, the adverse events of
GemCap were tolerable. In conclusion, Gem plus capecitabine
may be considered as promising chemotherapy for pancreatic
cancer. However, owing to the above limitations, more
convincing large-scale RCTs are needed.
Author contributions
Conceptualization: Guoqing Ouyang, Guangdong Pan.
Data curation: Zheng Zhou, Yongrong Wu.
Formal analysis: Zhen Liu, Wuhang Lu, Shuqing Hao.
Resources: Guangdong Pan.
Validation: Shuai Li.
Writing –original draft: Guoqing Ouyang, Guangdong Pan,
Yongrong Wu.
Writing –review & editing: Guangdong Pan
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