Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2015 Sep;34(3):429-41.
doi: 10.1007/s10555-015-9576-y.

Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis

N Haj Mohammad  1 , E ter Veer  2 , L Ngai  2 , R Mali  2 , M G H van Oijen  2 , H W M van Laarhoven  2
Affiliations
Meta-Analysis

Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma: triplet versus doublet chemotherapy: a systematic literature review and meta-analysis

N Haj Mohammad et al. Cancer Metastasis Rev. 2015 Sep.

Abstract

There is a debate whether triplet or doublet chemotherapy should be used as a first-line treatment in patients with advanced or metastatic esophagogastric cancer. Therefore, here we will review the available literature to assess the efficacy and safety of triplet versus doublet chemotherapy as a first-line treatment in patients with advanced esophagogastric cancer. We searched MEDLINE, Embase, and CENTRAL (Cochrane Central Register of Controlled Trials) between 1980 and March 2015 for randomized controlled phase II and III trials comparing triplet with doublet chemotherapy and abstracts of major oncology meetings from 1990 to 2014. Twenty-one studies with a total of 3475 participants were included in the meta-analysis for overall survival. An improvement in overall survival (OS) (hazard ratio (HR) 0.90, 95% confidence interval (CI) 0.83-0.97) and progression-free survival (PFS) (HR 0.80, 95% CI 0.69-0.93) was observed in favor of triplet. In addition, the use of triplet was associated with better objective response rate (ORR) (risk ratio 1.25, 95% CI 1.09-1.44) compared to doublet. The risks of grade 3-4 thrombocytopenia (6.2 vs 3.8%), infection (10.2 vs 6.4%), and mucositis (9.7 vs 4.7%) were statistically significantly increased with triplet compared to doublet. This review shows that first-line triplet therapy is superior to doublet therapy in patients with advanced esophagogastric cancer. However, the survival benefit is limited and the risks of grade 3-4 thrombocytopenia, infection, and mucositis are increased.

Keywords: Doublet chemotherapy; Esophageal cancer; First-line treatment; Gastric cancer; Palliative chemotherapy; Triplet chemotherapy.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
PRISMA flow diagram of literature search and study selection
Fig. 2
Fig. 2
When examining the subgroups, taxane and cisplatin showed a significant benefit
Fig. 3
Fig. 3
A significant benefit was observed for PFS in favor of a triplet, which was mainly based on the addition of a taxane to the doublet
Fig. 4
Fig. 4
The use of a triplet was associated with a better ORR compared to a doublet, which was mainly due to triplets with a fluoropyrimidine or taxane
Fig. 5
Fig. 5
Risk of bias assessment
Fig. 6
Fig. 6
Sensitivity analysis excluding those trials that were conducted in Asia
Fig. 7
Fig. 7
Sensitivity analysis excluding studies with “unknown” risk of bias on “random sequence” and “allocation concealment”
Fig. 8
Fig. 8
Sensitivity analysis excluding those trials that compared a triplet versus a doublet without the presence of two identical compounds in both arms
See this image and copyright information in PMC

References

    1. Al-Batran SE, Ajani JA. Impact of chemotherapy on quality of life in patients with metastatic esophagogastric cancer. Cancer. 2010;116(11):2511–8. - PubMed
    1. Murad AM, et al. Modified therapy with 5-fluorouracil, doxorubicin, and methotrexate in advanced gastric cancer. Cancer. 1993;72(1):37–41. doi: 10.1002/1097-0142(19930701)72:1<37::AID-CNCR2820720109>3.0.CO;2-P. - DOI - PubMed
    1. Pyrhonen S, et al. Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer. British Journal of Cancer. 1995;71(3):587–91. doi: 10.1038/bjc.1995.114. - DOI - PMC - PubMed
    1. Koizumi W, et al. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncology. 2008;9(3):215–21. doi: 10.1016/S1470-2045(08)70035-4. - DOI - PubMed
    1. Levi JA, et al. Analysis of a prospectively randomized comparison of doxorubicin versus 5-fluorouracil, doxorubicin, and BCNU in advanced gastric cancer: implications for future studies. Journal of Clinical Oncology. 1986;4(9):1348–55. - PubMed

MeSH terms

LinkOut - more resources