The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer

A systematic review and meta-analysis

Emil ter Veer, Nadia Haj Mohammad, P. Lodder, Lok Lam Ngai, Mary Samaan, Martijn. G. H. van Ooijen, Hanneke van Laarhoven

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Abstract

Background
S-1 is first-line therapy for advanced gastric cancer in Asia and is used with increased frequency in Western counties. We conducted a meta-analysis to investigate the efficacy and toxicity of S-1-based therapy compared with 5-fluorouracil (5-FU)/capecitabine-based therapy and S-1-based combination therapy compared with S-1 monotherapy.
Methods
MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology meeting abstracts, European Society for Medical Oncology meeting abstracts and ClinicalTrials.gov were searched for randomized clinical trials until May 2015. Data were extracted for overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and grade 1–2 and grade 3–4 adverse events. Stratified OS data for subgroups were extracted.
Results
-1 was not different from 5-FU (eight studies, n = 2788) in terms of OS [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.85–1.01] and PFS (HR 0.87, 95 % CI 0.73–1.04), whereas ORR was higher (risk ratio 1.43, 95 % CI 1.05–1.96). There was no subgroup difference in efficacy among Asian and Western patients, but in Western patients S-1 was associated with a lower rate of febrile neutropenia, toxicity-related deaths and grade 3–4 stomatitis and mucositis compared with 5-FU. S-1 showed no difference in efficacy compared with capecitabine (three studies, n = 329), but was associated with a lower rate of grade 3–4 neutropenia and grade 1–2 hand–foot syndrome. S-1-combination therapy was superior to S-1 monotherapy (eight studies, n = 1808) in terms of OS (HR 0.76, 95 % CI 0.65–0.90), PFS (HR 0.68, 95 % CI 0.56–0.82) and ORR (risk ratio 1.20, 95 % CI 1.04–1.38) but was more toxic. Survival benefit of S-1 combination therapy over S-1 monotherapy was most pronounced in patients with non-measurable disease, diffuse-type histological features and peritoneal metastasis.
Conclusions
S-1 is effective and tolerable as first-line therapy for advanced gastric cancer in both Asian and Western countries.
Keywords
Advanced gastric cancer, S-1, Chemotherapy, Meta-analysis
Original languageEnglish
Pages (from-to)696–712
JournalGastric Cancer
Volume19
Issue number3
DOIs
Publication statusPublished - 2016

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Confidence Intervals
Disease-Free Survival
Odds Ratio
Febrile Neutropenia
Mucositis
Neutropenia
Capecitabine

Cite this

ter Veer, Emil ; Mohammad, Nadia Haj ; Lodder, P. ; Ngai, Lok Lam ; Samaan, Mary ; van Ooijen, Martijn. G. H. ; van Laarhoven, Hanneke . / The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer : A systematic review and meta-analysis. In: Gastric Cancer. 2016 ; Vol. 19, No. 3. pp. 696–712.
@article{6fd986cdef1147168a513dd144870b7a,
title = "The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer: A systematic review and meta-analysis",
abstract = "BackgroundS-1 is first-line therapy for advanced gastric cancer in Asia and is used with increased frequency in Western counties. We conducted a meta-analysis to investigate the efficacy and toxicity of S-1-based therapy compared with 5-fluorouracil (5-FU)/capecitabine-based therapy and S-1-based combination therapy compared with S-1 monotherapy.MethodsMEDLINE, Embase, the Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology meeting abstracts, European Society for Medical Oncology meeting abstracts and ClinicalTrials.gov were searched for randomized clinical trials until May 2015. Data were extracted for overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and grade 1–2 and grade 3–4 adverse events. Stratified OS data for subgroups were extracted.Results-1 was not different from 5-FU (eight studies, n = 2788) in terms of OS [hazard ratio (HR) 0.93, 95 {\%} confidence interval (CI) 0.85–1.01] and PFS (HR 0.87, 95 {\%} CI 0.73–1.04), whereas ORR was higher (risk ratio 1.43, 95 {\%} CI 1.05–1.96). There was no subgroup difference in efficacy among Asian and Western patients, but in Western patients S-1 was associated with a lower rate of febrile neutropenia, toxicity-related deaths and grade 3–4 stomatitis and mucositis compared with 5-FU. S-1 showed no difference in efficacy compared with capecitabine (three studies, n = 329), but was associated with a lower rate of grade 3–4 neutropenia and grade 1–2 hand–foot syndrome. S-1-combination therapy was superior to S-1 monotherapy (eight studies, n = 1808) in terms of OS (HR 0.76, 95 {\%} CI 0.65–0.90), PFS (HR 0.68, 95 {\%} CI 0.56–0.82) and ORR (risk ratio 1.20, 95 {\%} CI 1.04–1.38) but was more toxic. Survival benefit of S-1 combination therapy over S-1 monotherapy was most pronounced in patients with non-measurable disease, diffuse-type histological features and peritoneal metastasis.ConclusionsS-1 is effective and tolerable as first-line therapy for advanced gastric cancer in both Asian and Western countries.KeywordsAdvanced gastric cancer, S-1, Chemotherapy, Meta-analysis",
author = "{ter Veer}, Emil and Mohammad, {Nadia Haj} and P. Lodder and Ngai, {Lok Lam} and Mary Samaan and {van Ooijen}, {Martijn. G. H.} and {van Laarhoven}, Hanneke",
year = "2016",
doi = "10.1007/s10120-015-0587-8",
language = "English",
volume = "19",
pages = "696–712",
journal = "Gastric Cancer",
issn = "1436-3291",
publisher = "Springer Japan",
number = "3",

}

The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer : A systematic review and meta-analysis. / ter Veer, Emil; Mohammad, Nadia Haj; Lodder, P.; Ngai, Lok Lam; Samaan, Mary; van Ooijen, Martijn. G. H. ; van Laarhoven, Hanneke .

In: Gastric Cancer, Vol. 19, No. 3, 2016, p. 696–712.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer

T2 - A systematic review and meta-analysis

AU - ter Veer, Emil

AU - Mohammad, Nadia Haj

AU - Lodder, P.

AU - Ngai, Lok Lam

AU - Samaan, Mary

AU - van Ooijen, Martijn. G. H.

AU - van Laarhoven, Hanneke

PY - 2016

Y1 - 2016

N2 - BackgroundS-1 is first-line therapy for advanced gastric cancer in Asia and is used with increased frequency in Western counties. We conducted a meta-analysis to investigate the efficacy and toxicity of S-1-based therapy compared with 5-fluorouracil (5-FU)/capecitabine-based therapy and S-1-based combination therapy compared with S-1 monotherapy.MethodsMEDLINE, Embase, the Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology meeting abstracts, European Society for Medical Oncology meeting abstracts and ClinicalTrials.gov were searched for randomized clinical trials until May 2015. Data were extracted for overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and grade 1–2 and grade 3–4 adverse events. Stratified OS data for subgroups were extracted.Results-1 was not different from 5-FU (eight studies, n = 2788) in terms of OS [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.85–1.01] and PFS (HR 0.87, 95 % CI 0.73–1.04), whereas ORR was higher (risk ratio 1.43, 95 % CI 1.05–1.96). There was no subgroup difference in efficacy among Asian and Western patients, but in Western patients S-1 was associated with a lower rate of febrile neutropenia, toxicity-related deaths and grade 3–4 stomatitis and mucositis compared with 5-FU. S-1 showed no difference in efficacy compared with capecitabine (three studies, n = 329), but was associated with a lower rate of grade 3–4 neutropenia and grade 1–2 hand–foot syndrome. S-1-combination therapy was superior to S-1 monotherapy (eight studies, n = 1808) in terms of OS (HR 0.76, 95 % CI 0.65–0.90), PFS (HR 0.68, 95 % CI 0.56–0.82) and ORR (risk ratio 1.20, 95 % CI 1.04–1.38) but was more toxic. Survival benefit of S-1 combination therapy over S-1 monotherapy was most pronounced in patients with non-measurable disease, diffuse-type histological features and peritoneal metastasis.ConclusionsS-1 is effective and tolerable as first-line therapy for advanced gastric cancer in both Asian and Western countries.KeywordsAdvanced gastric cancer, S-1, Chemotherapy, Meta-analysis

AB - BackgroundS-1 is first-line therapy for advanced gastric cancer in Asia and is used with increased frequency in Western counties. We conducted a meta-analysis to investigate the efficacy and toxicity of S-1-based therapy compared with 5-fluorouracil (5-FU)/capecitabine-based therapy and S-1-based combination therapy compared with S-1 monotherapy.MethodsMEDLINE, Embase, the Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology meeting abstracts, European Society for Medical Oncology meeting abstracts and ClinicalTrials.gov were searched for randomized clinical trials until May 2015. Data were extracted for overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and grade 1–2 and grade 3–4 adverse events. Stratified OS data for subgroups were extracted.Results-1 was not different from 5-FU (eight studies, n = 2788) in terms of OS [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.85–1.01] and PFS (HR 0.87, 95 % CI 0.73–1.04), whereas ORR was higher (risk ratio 1.43, 95 % CI 1.05–1.96). There was no subgroup difference in efficacy among Asian and Western patients, but in Western patients S-1 was associated with a lower rate of febrile neutropenia, toxicity-related deaths and grade 3–4 stomatitis and mucositis compared with 5-FU. S-1 showed no difference in efficacy compared with capecitabine (three studies, n = 329), but was associated with a lower rate of grade 3–4 neutropenia and grade 1–2 hand–foot syndrome. S-1-combination therapy was superior to S-1 monotherapy (eight studies, n = 1808) in terms of OS (HR 0.76, 95 % CI 0.65–0.90), PFS (HR 0.68, 95 % CI 0.56–0.82) and ORR (risk ratio 1.20, 95 % CI 1.04–1.38) but was more toxic. Survival benefit of S-1 combination therapy over S-1 monotherapy was most pronounced in patients with non-measurable disease, diffuse-type histological features and peritoneal metastasis.ConclusionsS-1 is effective and tolerable as first-line therapy for advanced gastric cancer in both Asian and Western countries.KeywordsAdvanced gastric cancer, S-1, Chemotherapy, Meta-analysis

U2 - 10.1007/s10120-015-0587-8

DO - 10.1007/s10120-015-0587-8

M3 - Article

VL - 19

SP - 696

EP - 712

JO - Gastric Cancer

JF - Gastric Cancer

SN - 1436-3291

IS - 3

ER -