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The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis

BACKGROUND: Gemcitabine (GEM) is used as a standard first-line drug to effectively alleviate symptoms and prolong survival time for advanced pancreatic cancer. Most randomized controlled trials (RCTs) show that GEM-based combination therapy is better than GEM alone, while some RCTs have the opposite...

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Autores principales: Zhang, Zhaohuan, He, Shuling, Wang, Ping, Zhou, Yibing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459213/
https://www.ncbi.nlm.nih.gov/pubmed/36092340
http://dx.doi.org/10.21037/jgo-22-624
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author Zhang, Zhaohuan
He, Shuling
Wang, Ping
Zhou, Yibing
author_facet Zhang, Zhaohuan
He, Shuling
Wang, Ping
Zhou, Yibing
author_sort Zhang, Zhaohuan
collection PubMed
description BACKGROUND: Gemcitabine (GEM) is used as a standard first-line drug to effectively alleviate symptoms and prolong survival time for advanced pancreatic cancer. Most randomized controlled trials (RCTs) show that GEM-based combination therapy is better than GEM alone, while some RCTs have the opposite conclusion. This study aimed to investigate whether GEM-based combination therapy would be superior to GEM alone by a systematic review and meta-analysis. METHODS: According to the PICOS principles, RCTs (S) focused on comparing GEM-based combination therapy (I) vs. GEM alone (C) for advanced pancreatic cancer (P) were collected from eight electronic databases, outcome variables mainly include survival status and adverse events (AEs) (O). Review Manager 5.4 was used to evaluate the pooled effects of the results among selected articles. Pooled estimate of hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were used as measures of effect sizes. Quality assessment for individual study was performed using the Cochrane tool for risk of bias. RESULTS: A total of 17 studies including 5,197 patients were selected in this analysis. The pooled results revealed that GEM-based combination therapy significantly improved the overall survival (OS; HR =0.84; 95% CI: 0.79 to 0.90; P<0.00001), progression-free survival (PFS; HR =0.78; 95% CI: 0.72 to 0.84; P<0.00001), overall response rate (ORR; OR =1.92; 95% CI: 1.61 to 2.30; P<0.00001), 1-year survival rate (OR =1.44; 95% CI: 1.02 to 2.03; P=0.04), respectively. Subgroup analysis showed that the efficacy of GEM plus capecitabine (CAP) and GEM plus S-1 was better than that of GEM alone, while GEM plus cisplatin (CIS) did not achieve an improved effect. GEM-based combination therapy can significantly increase the incidence of AEs, such as leukopenia (P<0.001), neutropenia (P<0.001), anemia (P<0.05), nausea (P<0.001), diarrhea (P<0.05), and stomatitis (P<0.001). No publication bias existed in our meta-analysis (P>0.10). DISCUSSION: Our study supported that GEM-based combination therapy was more beneficial to improve patient’s survival than GEM alone, while there was no additional benefits in GEM plus CIS. We also found that GEM-based combination therapy increased the incidence of AEs. Clinicians need to choose the appropriate combination therapy according to the specific situation.
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spelling pubmed-94592132022-09-10 The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis Zhang, Zhaohuan He, Shuling Wang, Ping Zhou, Yibing J Gastrointest Oncol Original Article BACKGROUND: Gemcitabine (GEM) is used as a standard first-line drug to effectively alleviate symptoms and prolong survival time for advanced pancreatic cancer. Most randomized controlled trials (RCTs) show that GEM-based combination therapy is better than GEM alone, while some RCTs have the opposite conclusion. This study aimed to investigate whether GEM-based combination therapy would be superior to GEM alone by a systematic review and meta-analysis. METHODS: According to the PICOS principles, RCTs (S) focused on comparing GEM-based combination therapy (I) vs. GEM alone (C) for advanced pancreatic cancer (P) were collected from eight electronic databases, outcome variables mainly include survival status and adverse events (AEs) (O). Review Manager 5.4 was used to evaluate the pooled effects of the results among selected articles. Pooled estimate of hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were used as measures of effect sizes. Quality assessment for individual study was performed using the Cochrane tool for risk of bias. RESULTS: A total of 17 studies including 5,197 patients were selected in this analysis. The pooled results revealed that GEM-based combination therapy significantly improved the overall survival (OS; HR =0.84; 95% CI: 0.79 to 0.90; P<0.00001), progression-free survival (PFS; HR =0.78; 95% CI: 0.72 to 0.84; P<0.00001), overall response rate (ORR; OR =1.92; 95% CI: 1.61 to 2.30; P<0.00001), 1-year survival rate (OR =1.44; 95% CI: 1.02 to 2.03; P=0.04), respectively. Subgroup analysis showed that the efficacy of GEM plus capecitabine (CAP) and GEM plus S-1 was better than that of GEM alone, while GEM plus cisplatin (CIS) did not achieve an improved effect. GEM-based combination therapy can significantly increase the incidence of AEs, such as leukopenia (P<0.001), neutropenia (P<0.001), anemia (P<0.05), nausea (P<0.001), diarrhea (P<0.05), and stomatitis (P<0.001). No publication bias existed in our meta-analysis (P>0.10). DISCUSSION: Our study supported that GEM-based combination therapy was more beneficial to improve patient’s survival than GEM alone, while there was no additional benefits in GEM plus CIS. We also found that GEM-based combination therapy increased the incidence of AEs. Clinicians need to choose the appropriate combination therapy according to the specific situation. AME Publishing Company 2022-08 /pmc/articles/PMC9459213/ /pubmed/36092340 http://dx.doi.org/10.21037/jgo-22-624 Text en 2022 Journal of Gastrointestinal Oncology. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Zhang, Zhaohuan
He, Shuling
Wang, Ping
Zhou, Yibing
The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis
title The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis
title_full The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis
title_fullStr The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis
title_full_unstemmed The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis
title_short The efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis
title_sort efficacy and safety of gemcitabine-based combination therapy vs. gemcitabine alone for the treatment of advanced pancreatic cancer: a systematic review and meta-analysis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9459213/
https://www.ncbi.nlm.nih.gov/pubmed/36092340
http://dx.doi.org/10.21037/jgo-22-624
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