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For: Wang X, Wang ML, Zhou LY, Lu XY, Yang JF, Yu HG. Randomized phase II study comparing paclitaxel with S-1 vs. S-1 as first-line treatment in patients with advanced gastric cancer. Clin Transl Oncol 2013;15:836-842. [PMID: 23381898 DOI: 10.1007/s12094-013-1012-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 01/21/2013] [Indexed: 12/14/2022]

For:	Wang X, Wang ML, Zhou LY, Lu XY, Yang JF, Yu HG. Randomized phase II study comparing paclitaxel with S-1 vs. S-1 as first-line treatment in patients with advanced gastric cancer. Clin Transl Oncol 2013;15:836-842. [PMID: 23381898 DOI: 10.1007/s12094-013-1012-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2012] [Accepted: 01/21/2013] [Indexed: 12/14/2022]

Number

Cited by Other Article(s)

Dai YH, Yu XJ, Xu HT, Zhuang L, Zhang MS, Zou YM, Fu Q, Qiu H, Yuan XL. Nab-paclitaxel plus S-1 versus oxaliplatin plus S-1 as first-line treatment in advanced gastric cancer: results of a multicenter, randomized, phase III trial (GAPSO study). Ther Adv Med Oncol 2022;14:17588359221118020. [PMID: 35983025 PMCID: PMC9379568 DOI: 10.1177/17588359221118020] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 07/18/2022] [Indexed: 11/17/2022] Open

Abstract

Background:

This study aimed to investigate the superiority of nab-paclitaxel plus S-1 (AS) over oxaliplatin plus S-1 (SOX) in patients with advanced gastric cancer (AGC).

Methods:

In this multicenter, randomized, phase III superiority trial, eligible patients with unresectable, locally advanced gastric adenocarcinoma were recruited and randomly assigned (1:1) to receive AS (nab-paclitaxel 260 mg/m² on day 1 or 130 mg/m² on days 1 and 8; oral S-1 40–60 mg twice daily for 14 days) or SOX (130 mg/m² oxaliplatin on day 1; oral S-1 40–60 mg twice daily for 14 days) every 3 weeks for up to six cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival, objective response rate, and safety.

Results:

Owing to slow enrolment, an unplanned interim analysis was performed, resulting in the early termination of the study on 31 December 2021 (data cutoff). Between March 2019 and March 2021, 97 patients (AS, n = 48; SOX, n = 49) were treated and evaluated for efficacy and safety of AS and SOX. As of the data cutoff, the median follow-up was 23.13 months [95% confidence interval (CI), 13.39–32.87]. The median PFS was 9.03 months (95% CI, 6.50–11.56) in the AS group and 5.07 months (95% CI, 4.33–5.81) in the SOX group, demonstrating a better PFS tendency following AS treatment than SOX treatment (hazard ratio = 0.59; 95% CI, 0.37–0.94; p = 0.03). The most common grade 3 or worse adverse events were anemia, neutropenia, and leukopenia in both groups, with a higher incidence of thrombocytopenia in the SOX group.

Conclusion:

Although this study was terminated early, the results demonstrated a better PFS tendency in patients with AGC who were treated with AS than in those treated with SOX, with controllable toxicities.

Trial registration:

Clinical Trials.gov identifiers: NCT03801668. Registered January 11, 2019.

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Yu S, Cai L, Lin F, Wu X, Zhang C, Liu X, Li W. Durable Response After Combination Of Concurrent Chemoradiotherapy And Anti-PD-1 Therapy In HER2-Negative Advanced Gastric Adenocarcinoma: A Case Report. Onco Targets Ther 2019;12:7691-7698. [PMID: 31571920 PMCID: PMC6757230 DOI: 10.2147/ott.s221436] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2019] [Accepted: 09/03/2019] [Indexed: 12/26/2022] Open

Ngai LL, ter Veer E, van den Boorn HG, van Herk EH, van Kleef JJ, van Oijen MGH, van Laarhoven HWM. TOXview: a novel graphical presentation of cancer treatment toxicity profiles. Acta Oncol 2019;58:1138-1148. [PMID: 31017020 DOI: 10.1080/0284186x.2019.1601256] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

Abstract

Background: Toxicity profiles play a crucial role in the choice between specific palliative chemotherapy regimens. To optimize the quality of life for cancer patients, patients should be adequately informed about potential toxicities before undergoing chemotherapy. Therefore, we constructed TOXviews, a novel graphical presentation and overview of toxicity profiles to improve information provision about adverse events. As an example, we analyzed first-line chemotherapy regimens for advanced esophagogastric cancer (AEGC). Methods: We searched PubMed, EMBASE, CENTRAL, ASCO and ESMO for prospective phase II or III randomized controlled trials (RCTs) on palliative first-line systemic treatment for AEGC until February 2017. We extracted proportions of Common Terminology Criteria for Adverse Events grade 1-2 (mild) and 3-4 (severe) adverse events from each chemotherapy arm and pooled these by using single-arm meta-analysis. Toxicity profiles per chemotherapy regimen were visualized in bidirectional bar charts with pooled proportions plus 95% confidence intervals. For comparative analysis, chemotherapy regimens were grouped in singlets, doublets and triplets. Results: We included 92 RCTs with a total of 16,963 patients. TOXviews for 3 fluoropyrimidine singlets, 5 cisplatin-containing doublets (C-doublets), 10 fluoropyrimidine non-cisplatin containing doublets (F-doublets), 4 anthracycline-containing triplets (A-triplets) and 5 taxane-containing triplets (T-triplets) were constructed. C-doublets, A-triplets and T-triplets all showed an increased incidence of grade 3-4 adverse events and clinically relevant grade 1-2 adverse events compared to F-doublets. Conclusion: TOXview provides a new graphical presentation and overview of chemotherapy toxicities. TOXviews can be used to educate physicians about the incidences of AEs of systemic therapy and improve informed decision-making.

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Chen L, Hao Y, Cong X, Zou M, Li S, Zhu L, Song H, Xue Y. Peripheral Venous Blood Platelet-to-Lymphocyte Ratio (PLR) for Predicting the Survival of Patients With Gastric Cancer Treated With SOX or XELOX Regimen Neoadjuvant Chemotherapy. Technol Cancer Res Treat 2019;18:1533033819829485. [PMID: 30760114 PMCID: PMC6378642 DOI: 10.1177/1533033819829485] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open

Abstract

Background:

Inflammation plays an important role in tumor progression. Predicting survival is remarkably difficult in patients with gastric cancer receiving neoadjuvant chemotherapy. The aim of the present study is to investigate the potential prognostic significance of the platelet-to-lymphocyte ratio in patients with gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen.

Methods:

Ninety-one patients with gastric cancer treated with neoadjuvant chemotherapy were enrolled in this study and then underwent operation. The optimal cutoff value was calculated using receiver-operating characteristic curve analyses. The optimal cutoff value of platelet-to-lymphocyte ratio was divided into low platelet-to-lymphocyte ratio <162 group and high platelet-to-lymphocyte ratio ≥162 group. Kaplan-Meier method and log-rank test were used to analyze the survival curves. The independent prognostic factors and prognostic value of the platelet-to-lymphocyte ratio were assessed by univariate and multivariate Cox proportional hazards regression model. The toxicity was evaluated according to the National Cancer Institute Common Toxicity Criteria.

Results:

Kaplan-Meier analyses revealed that patients with low platelet-to-lymphocyte ratio correlated remarkably with better mean disease-free survival and mean overall survival than those with high platelet-to-lymphocyte ratio (mean disease-free survival 47.33 and 33.62 months, respectively; mean overall survival 51.21 and 36.80 months, respectively). The results demonstrated that platelet-to-lymphocyte ratio had prognostic significance using the cutoff value of 162 on disease-free survival and overall survival, and the mean disease-free survival and overall survival time for patients with low platelet-to-lymphocyte ratio were longer than those with high platelet-to-lymphocyte ratio. Meanwhile, patients with gastric cancer who had lower platelet-to-lymphocyte ratio had longer 1-, 3-, and 5-year rates of disease-free survival and overall survival. Moreover, patients with low platelet-to-lymphocyte ratio had longer mean disease-free survival and overall survival than those with high platelet-to-lymphocyte ratio in receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen.

Conclusions:

The preoperative platelet-to-lymphocyte ratio may be a promising and convenient prognostic biomarker for patients gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen neoadjuvant chemotherapy. It may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.

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S-1 combined with paclitaxel may benefit advanced gastric cancer: Evidence from a systematic review and meta-analysis. Int J Surg 2019;62:34-43. [PMID: 30641155 DOI: 10.1016/j.ijsu.2018.11.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Revised: 10/13/2018] [Accepted: 11/07/2018] [Indexed: 12/15/2022]

Abstract

BACKGROUND

Gastric cancer, as one of the increasingly common malignancies, has experienced high morbidity throughout many countries at present. Currently, chemotherapy regimen with more efficacy and safety for advanced gastric cancer (AGC) is needed. We aimed to assess the clinical efficacy and safety of S-1 combined with paclitaxel (PTX) for AGC by performing a systematic review and meta-analysis of the published studies.

METHOD

All published randomized controlled trials (RCTs) of S-1 combined with PTX for AGC were searched. Studies that included patients with locally advanced or metastases' gastric cancers were included. We searched the databases included Cochrane Library of Clinical Comparative Trials, MEDLINE, Embase, American Society of Clinical Oncology meeting abstracts and China National Knowledge Internet (CNKI) from 2000 to 2018. We searched the database up to January 2018. The first endpoint was overall survival (OS). Other endpoints were progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Safety analyses were also performed.

RESULTS

A total of 7 trials (including 1407 patients, 711 patients in intervention group and 696 patients in control group) were included in the present analysis. S-1 combined with PTX significantly improved the OS [HR = 0.78, 95% CI: 0.60-0.97, P = 0.000],PFS [HR = 0.70, 95% CI: 0.55-0.85, P = 0.000], ORR [RR = 1.30, 95%CI: 1.05-1.60, P = 0.017] and DCR [RR = 1.15, 95%CI: 1.04-1.27, P = 0.008] of patients with AGC. The grade 3 or 4 haematological and non-hematologic toxicities were anemia [RR = 1.71, 95% CI: 1.04-2.79, P = 0.03], neutropenia [RR = 1.65, 95% CI: 1.32-2.06, P < 0.0001] and anorexia [RR = 1.66, 95% CI: 1.05-2.64, P = 0.03] respectively.

CONCLUSION

S-1 combined with PTX may be a good choice for patients with AGC. S-1 plus PTX experienced more efficacy and safety when compared with S-1 alone or S-1 plus other drugs.

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Ter Veer E, van Kleef JJ, Schokker S, van der Woude SO, Laarman M, Haj Mohammad N, Sprangers MAG, van Oijen MGH, van Laarhoven HWM. Prognostic and predictive factors for overall survival in metastatic oesophagogastric cancer: A systematic review and meta-analysis. Eur J Cancer 2018;103:214-226. [PMID: 30268922 DOI: 10.1016/j.ejca.2018.07.132] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2018] [Revised: 07/26/2018] [Accepted: 07/31/2018] [Indexed: 02/07/2023]

Abstract

BACKGROUND

Consistent evidence on prognostic and predictive factors for advanced oesophagogastric cancer is lacking. Therefore, we performed a systematic review and meta-analysis.

METHODS

We searched PubMed, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL) databases for phase II/III randomised controlled trials (RCTs) until February 2017 on palliative systemic therapy for advanced oesophagogastric cancer that reported prognostic or predictive factors for overall survival (PROSPERO-CRD42014015177). Prognostic factors were identified from multivariate regression analyses in study reports. Factors were considered potentially clinically relevant if statistically significant (P ≤ 0.05) in multivariate analysis in ≥50% of the total number of patients in the pooled sample of the RCTs and were reported with a pooled sample size of ≥600 patients in the first-line or ≥300 patients in the beyond first-line setting. Predictive factors were identified from time-to-event stratified treatment comparisons and deemed potentially clinically relevant if the P-value for interaction between subgroups was ≤0.20 and the hazard ratio in one of the subgroups was significant (P ≤ 0.05).

RESULTS

Forty-six original RCTs were included (n = 15,392 patients) reporting on first-line (n = 33) and beyond first-line therapy (n = 13). Seventeen prognostic factors for overall survival in the first-line and four in the beyond first-line treatment setting were potentially clinically relevant. Twenty-one predictive factors in first-line and nine in beyond first-line treatment setting were potentially relevant regarding treatment efficacy.

CONCLUSIONS

The prognostic and predictive factors identified in this systematic review can be used to characterise patients in clinical practice, be included in future trial designs, enrich prognostic tools and generate hypotheses to be tested in future research to promote patient-centred treatment.

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Wagner AD, Syn NLX, Moehler M, Grothe W, Yong WP, Tai B, Ho J, Unverzagt S, Cochrane Upper GI and Pancreatic Diseases Group. Chemotherapy for advanced gastric cancer. Cochrane Database Syst Rev 2017;8:CD004064. [PMID: 28850174 PMCID: PMC6483552 DOI: 10.1002/14651858.cd004064.pub4] [Citation(s) in RCA: 407] [Impact Index Per Article: 50.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]

Abstract

BACKGROUND

Gastric cancer is the fifth most common cancer worldwide. In "Western" countries, most people are either diagnosed at an advanced stage, or develop a relapse after surgery with curative intent. In people with advanced disease, significant benefits from targeted therapies are currently limited to HER-2 positive disease treated with trastuzumab, in combination with chemotherapy, in first-line. In second-line, ramucirumab, alone or in combination with paclitaxel, demonstrated significant survival benefits. Thus, systemic chemotherapy remains the mainstay of treatment for advanced gastric cancer. Uncertainty remains regarding the choice of the regimen.

OBJECTIVES

To assess the efficacy of chemotherapy versus best supportive care (BSC), combination versus single-agent chemotherapy and different chemotherapy combinations in advanced gastric cancer.

SEARCH METHODS

We searched the Cochrane Central Register of Controlled Trials, MEDLINE and Embase up to June 2016, reference lists of studies, and contacted pharmaceutical companies and experts to identify randomised controlled trials (RCTs).

SELECTION CRITERIA

We considered only RCTs on systemic, intravenous or oral chemotherapy versus BSC, combination versus single-agent chemotherapy and different chemotherapy regimens in advanced gastric cancer.

DATA COLLECTION AND ANALYSIS

Two review authors independently identified studies and extracted data. A third investigator was consulted in case of disagreements. We contacted study authors to obtain missing information.

MAIN RESULTS

We included 64 RCTs, of which 60 RCTs (11,698 participants) provided data for the meta-analysis of overall survival. We found chemotherapy extends overall survival (OS) by approximately 6.7 months more than BSC (hazard ratio (HR) 0.3, 95% confidence intervals (CI) 0.24 to 0.55, 184 participants, three studies, moderate-quality evidence). Combination chemotherapy extends OS slightly (by an additional month) versus single-agent chemotherapy (HR 0.84, 95% CI 0.79 to 0.89, 4447 participants, 23 studies, moderate-quality evidence), which is partly counterbalanced by increased toxicity. The benefit of epirubicin in three-drug combinations, in which cisplatin is replaced by oxaliplatin and 5-FU is replaced by capecitabine is unknown.Irinotecan extends OS slightly (by an additional 1.6 months) versus non-irinotecan-containing regimens (HR 0.87, 95% CI 0.80 to 0.95, 2135 participants, 10 studies, high-quality evidence).Docetaxel extends OS slightly (just over one month) compared to non-docetaxel-containing regimens (HR 0.86, 95% CI 0.78 to 0.95, 2001 participants, eight studies, high-quality evidence). However, due to subgroup analyses, we are uncertain whether docetaxel-containing combinations (docetaxel added to a single-agent or two-drug combination) extends OS due to moderate-quality evidence (HR 0.80, 95% CI 0.71 to 0.91, 1466 participants, four studies, moderate-quality evidence). When another chemotherapy was replaced by docetaxel, there is probably little or no difference in OS (HR 1.05; 0.87 to 1.27, 479 participants, three studies, moderate-quality evidence). We found there is probably little or no difference in OS when comparing capecitabine versus 5-FU-containing regimens (HR 0.94, 95% CI 0.79 to 1.11, 732 participants, five studies, moderate-quality evidence) .Oxaliplatin may extend (by less than one month) OS versus cisplatin-containing regimens (HR 0.81, 95% CI 0.67 to 0.98, 1105 participants, five studies, low-quality evidence). We are uncertain whether taxane-platinum combinations with (versus without) fluoropyrimidines extend OS due to very low-quality evidence (HR 0.86, 95% CI 0.71 to 1.06, 482 participants, three studies, very low-quality evidence). S-1 regimens improve OS slightly (by less than an additional month) versus 5-FU-containing regimens (HR 0.91, 95% CI 0.83 to 1.00, 1793 participants, four studies, high-quality evidence), however since S-1 is used in different doses and schedules between Asian and non-Asian population, the applicability of this finding to individual populations is uncertain.

AUTHORS' CONCLUSIONS

Chemotherapy improves survival (by an additional 6.7 months) in comparison to BSC, and combination chemotherapy improves survival (by an additional month) compared to single-agent 5-FU. Testing all patients for HER-2 status may help to identify patients with HER-2-positive tumours, for whom, in the absence of contraindications, trastuzumab in combination with capecitabine or 5-FU in combination with cisplatin has been shown to be beneficial. For HER-2 negative people, all different two-and three-drug combinations including irinotecan, docetaxel, oxaliplatin or oral 5-FU prodrugs are valid treatment options for advanced gastric cancer, and consideration of the side effects of each regimen is essential in the treatment decision. Irinotecan-containing combinations and docetaxel-containing combinations (in which docetaxel was added to a single-agent or two-drug (platinum/5-FUcombination) show significant survival benefits in the comparisons studied above. Furthermore, docetaxel-containing three-drug regimens have increased response rates, but the advantages of the docetaxel-containing three-drug combinations (DCF, FLO-T) are counterbalanced by increased toxicity. Additionally, oxaliplatin-containing regimens demonstrated a benefit in OS as compared to the same regimen containing cisplatin, and there is a modest survival improvement of S-1 compared to 5-FU-containing regimens.Whether the survival benefit for three-drug combinations including cisplatin, 5-FU, and epirubicin as compared to the same regimen without epirubicin is still valid when second-line therapy is routinely administered and when cisplatin is replaced by oxaliplatin and 5-FU by capecitabine is questionable. Furthermore, the magnitude of the observed survival benefits for the three-drug regimens is not large enough to be clinically meaningful as defined recently by the American Society for Clinical Oncology (Ellis 2014). In contrast to the comparisons in which a survival benefit was observed by adding a third drug to a two-drug regimen at the cost of increased toxicity, the comparison of regimens in which another chemotherapy was replaced by irinotecan was associated with a survival benefit (of borderline statistical significance), but without increased toxicity. For this reason irinotecan/5-FU-containing combinations are an attractive option for first-line treatment. Although they need to be interpreted with caution, subgroup analyses of one study suggest that elderly people have a greater benefit form oxaliplatin, as compared to cisplatin-based regimens, and that people with locally advanced disease or younger than 65 years might benefit more from a three-drug regimen including 5-FU, docetaxel, and oxaliplatin as compared to a two-drug combination of 5-FU and oxaliplatin, a hypothesis that needs further confirmation. For people with good performance status, the benefit of second-line chemotherapy has been established in several RCTs.

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Shi J, Gao P, Song Y, Chen X, Li Y, Zhang C, Wang H, Wang Z. Efficacy and safety of taxane-based systemic chemotherapy of advanced gastric cancer: A systematic review and meta-analysis. Sci Rep 2017;7:5319. [PMID: 28706257 PMCID: PMC5509659 DOI: 10.1038/s41598-017-05464-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Accepted: 05/31/2017] [Indexed: 02/07/2023] Open

Sun J, Ren Z, Sun X, Hou H, Li K, Ge Q. Efficacy and safety comparison of chemotherapies for advanced gastric cancer: A network meta-analysis. Oncotarget 2017;8:39673-39682. [PMID: 28562333 PMCID: PMC5503642 DOI: 10.18632/oncotarget.17784] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2017] [Accepted: 04/03/2017] [Indexed: 12/12/2022] Open

Duo-Ji MM, Ci-Ren BS, Long ZW, Zhang XH, Luo DL. Short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer: a network meta-analysis. Oncotarget 2017;8:37896-37911. [PMID: 28099947 PMCID: PMC5514960 DOI: 10.18632/oncotarget.14664] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 11/14/2016] [Indexed: 01/13/2023] Open

Chen L, Zuo Y, Zhu L, Zhang Y, Li S, Ma F, Han Y, Song H, Xue Y. Peripheral venous blood neutrophil-to-lymphocyte ratio predicts survival in patients with advanced gastric cancer treated with neoadjuvant chemotherapy. Onco Targets Ther 2017;10:2569-2580. [PMID: 28553122 PMCID: PMC5440079 DOI: 10.2147/ott.s134716] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open

Abstract

Background

Accurate and useful predictors of gastric carcinoma treated with neoadjuvant chemotherapy are lacking at present. We aim to explore the potential prognostic significance of the neutrophil-to-lymphocyte ratio (NLR) in advanced gastric cancer receiving S-1 plus oxaliplatin (SOX) or oxaliplatin and capecitabine (XELOX) regimen.

Methods

We enrolled 91 patients with advanced gastric cancer treated with neoadjuvant chemotherapy from August 2008 to September 2015. The peripheral venous blood samples were collected before neoadjuvant chemotherapy. The NLR was divided into two groups: low NLR <2.17 group and high NLR ≥2.17 group. Univariate analysis on disease-free survival (DFS) and overall survival (OS) were generated using the Kaplan–Meier method and compared using the log-rank test. Prognostic factors were assessed by univariate analyses, and the independent prognostic factors were evaluated using multivariate analysis (Cox’s proportional-hazards regression model).

Results

The univariate analysis showed that median DFS and median OS were worse for high NLR values than low NLR values before neoadjuvant chemotherapy (median DFS: 19.97 and 26.87 months, respectively, P=0.299; median OS: 25.83 and 29.73 months, respectively, P=0.405). Multivariate analysis showed that the NLR before neoadjuvant chemotherapy was not an independent prognostic factor for DFS and OS. However, median DFS and median OS were worse for high neutrophil values than for low neutrophil values (median DFS: 21.03 and 26.87 months, respectively, P=0.396; median OS: 24.43 and 29.37 months, respectively, P=0.534); for low lymphocyte values than for high lymphocyte values before neoadjuvant chemotherapy (median DFS: 22.33 and 26.87 months, respectively, P=0.624; median OS: 26.37 and 27.93 months, respectively, P=0.584). Nevertheless, patients with low NLR had better 1-year, 3-year, and 5-year DFS and OS rates.

Conclusion

NLR may serve as a cheap and convenient prognostic indicator in gastric carcinoma patients receiving SOX or XELOX neoadjuvant chemotherapy. Low NLR may help the doctors to take efficient treatment measures for gastric cancer.

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Antagonism of miRNA-21 Sensitizes Human Gastric Cancer Cells to Paclitaxel. Cell Biochem Biophys 2016;72:275-82. [PMID: 27040946 DOI: 10.1007/s12013-014-0450-2] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

Ter Veer E, Haj Mohammad N, van Valkenhoef G, Ngai LL, Mali RMA, Anderegg MC, van Oijen MGH, van Laarhoven HWM. The Efficacy and Safety of First-line Chemotherapy in Advanced Esophagogastric Cancer: A Network Meta-analysis. J Natl Cancer Inst 2016;108:djw166. [PMID: 27576566 DOI: 10.1093/jnci/djw166] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Accepted: 05/27/2016] [Indexed: 12/12/2022] Open

Abstract

BACKGROUND

A globally accepted standard first-line chemotherapy regimen in advanced esophagogastric cancer (AEGC) is not clearly established. We conducted a systematic review to investigate the efficacy and safety of first-line chemotherapy using Network meta-analysis (NMA).

METHODS

Medline, EMBASE, CENTRAL, and conferences were searched until June 2015 for randomized controlled trials that compared regimens containing: fluoropyrimidine (F), platinum (cisplatin [C] and oxaliplatin [Ox]), taxane (T), anthracycline (A), irinotecan (I), or methotrexate (M). Direct and indirect evidence for overall survival (OS) and progression-free-survival (PFS) were combined using random-effects NMA on the hazard ratio (HR) scale and calculated as combined hazard ratios and 95% credible intervals (CrIs).

RESULTS

The NMA incorporated 17 chemotherapy regimens with 37 direct comparisons between regimens for OS (50 studies, n = 10 249) and 29 direct comparisons for PFS (34 studies, n = 7795). Combining direct and indirect effects showed increased efficacy for fluoropyrimidine noncisplatin doublets (F-doublets) over cisplatin doublets (C-doublets): FI vs CF (combined HR = 0.85, 95% CrI = 0.71 to 0.99), FOx vs CF (combined HR = 0.83, 95% CrI = 0.71 to 0.98) in OS and FOx vs CF (combined HR = 0.82, 95% CrI = 0.66 to 0.99) in PFS. Anthracycline-containing triplets (A-triplets: ACF, AFOx, AFM) and TCF triplet showed no benefit over F-doublets in OS and PFS. The triplet FOxT showed increased PFS vs F-doublets FT (combined HR = 0.61, 95% CrI = 0.38 to 0.99), FI (combined HR = 0.62, 95% CrI = 0.38 to 0.99), and FOx (combined HR = 0.67, 95% CrI = 0.44 to 0.99). Increased grade 3 to 4 toxicity was found for CF vs F-doublets, for ACF vs FI for TCF vs CF, and for FOxT vs FOx.

CONCLUSIONS

Based on efficacy and toxicity, F-doublets FOx, FI, and FT are preferred as first-line treatment for AEGC compared with C-doublets, A-triplets, and TCF. FOxT is the most promising triplet.

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Affiliation(s)

Emil Ter Veer Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV)
Nadia Haj Mohammad Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV)
Gert van Valkenhoef Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV)
Lok Lam Ngai Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV)
Rosa M A Mali Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV)
Maarten C Anderegg Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV)
Martijn G H van Oijen Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV)
Hanneke W M van Laarhoven Affiliations of author: Department of Medical Oncology (EtV, NHM, LLN, RM, MGHvO, HWMvL) and Department of Surgery (MCA), Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands; Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands (GvV)

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Ter Veer E, Mohammad NH, Lodder P, Ngai LL, Samaan M, van Oijen MGH, van Laarhoven HWM. The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer: a systematic review and meta-analysis. Gastric Cancer 2016;19:696-712. [PMID: 26754295 PMCID: PMC4906062 DOI: 10.1007/s10120-015-0587-8] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2015] [Accepted: 12/07/2015] [Indexed: 02/07/2023]

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

S-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.

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Chen XD, He FQ, Chen M, Tang LC, Tang XL. Can S-1 replace fluorouracil for advanced gastric cancer? A PRISMA-compliant systematic review and meta-analysis. Medicine (Baltimore) 2016;95:e3916. [PMID: 27310997 PMCID: PMC4998483 DOI: 10.1097/md.0000000000003916] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Revised: 05/05/2016] [Accepted: 05/11/2016] [Indexed: 02/05/2023] Open

Abstract

It remains to be seen whether S-1 can be a replacement for infusional fluorouracil (5-FU) for advanced gastric cancer (AGC). The aim of this study was to compare the efficacy and safety of S-1 with 5-FU in AGC.PubMed and Cochrane Library were searched. Randomized controlled trials and meta-analyses comparing S-1 with 5-FU for AGC were eligible. Meta-analysis was performed using RevMan 5.2.Seven trials involving 2443 patients were included. Compared with 5-FU, S-1 showed no significant prolongation of overall survival (OS) (hazard ratio [HR] = 0.91, 95% confidence interval [CI] [0.83-1.01], P = 0.07) and progression-free survival (HR = 0.89, 95% CI [0.70-1.13], P = 0.35), but longer time to treatment failure (HR = 0.74, 95% CI [0.56-0.97], P = 0.03). The objective response rates were comparable (risk ratio [RR] = 1.36, 95% CI [0.95, 1.96], P = 0.10). Regarding treatment-related deaths and hematological toxicities, there was significant heterogeneity between Asian and non-Asian trials, and subgroup analysis was applied. In Asian patients, there was a significant increase in hematological toxicities such as leukopenia (grade 1-4: RR = 1.22, 95% CI [1.08, 1.37], P = 0.001; grade 3-4: RR = 2.21, 95% CI [1.52, 3.21], P < 0.0001), neutropenia (grade 1-4: RR = 1.29, 95% CI [1.11, 1.48], P = 0.0005; grade 3-4: RR = 1.87, 95% CI [1.11, 3.17], P = 0.02), and thrombocytopenia (grade 1-4: RR = 1.71, 95% CI [1.22, 2.41], P = 0.002) in S-1-containing regimens compared with 5-FU-containing regimens, but without significant difference in treatment-related mortality rate (risk difference [RD] = 0.00, 95% CI [-0.01, 0.01], P = 0.68). In non-Asian patients, S-1-containing regimens were, however, associated with significantly fewer treatment-related deaths (RD = -0.02, 95% CI [-0.05, -0.00], P = 0.04), as well as less all grade 1-4 and grade 3-4 hematological toxicities except anemia. There was no significant heterogeneity in nonhematologic toxicities between Asian and non-Asian trials. Lower incidence of grade 1-4 nausea, diarrhea, mucositis, grade 3-4 mucositis, increased creatinine, and decreased calculated creatinine clearance was observed in S-1-containing regimens.S-1 could not improve OS, but increase some hematological toxicities in Asian patients. Therefore, special attention on hematological toxicities should be paid to Asian patients because S-1 is administered on an outpatient basis.

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Wang L, Song Q, Li J, Chen X. S-1 treatment leading to complete remission of advanced duodenal adenocarcinoma: A case report. Mol Clin Oncol 2015;3:1184-1186. [PMID: 26623074 DOI: 10.3892/mco.2015.607] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2015] [Accepted: 07/09/2015] [Indexed: 12/29/2022] Open

Di Vita M, Cappellani A, Piccolo G, Zanghì A, Cavallaro A, Bertola G, Bolognese A, Facchini G, D'Aniello C, Di Francia R, Cardì F, Berretta M. The role of HIPEC in the treatment of peritoneal carcinomatosis from gastric cancer: between lights and shadows. Anticancer Drugs 2015;26:123-138. [PMID: 25406023 DOI: 10.1097/cad.0000000000000179] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Liu H, Chen X, Sun J, Gao P, Song Y, Zhang N, Lu X, Xu H, Wang Z. The efficacy and toxicity of paclitaxel plus S-1 compared with paclitaxel plus 5-FU for advanced gastric cancer: a PRISMA systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore) 2014;93:e164. [PMID: 25437030 PMCID: PMC4616381 DOI: 10.1097/md.0000000000000164] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open

Zhang ZD, Kong Y, Yang W, Zhang B, Zhang YL, Ma EM, Liu HX, Chen XB, Hua YW. Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer. World J Surg Oncol 2014;12:115. [PMID: 24758484 PMCID: PMC4020605 DOI: 10.1186/1477-7819-12-115] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2014] [Accepted: 04/07/2014] [Indexed: 02/21/2023] Open

Zhang ZD, Kong Y, Yang W, Zhang B, Zhang YL, Ma EM, Liu HX, Chen XB, Hua YW. Clinical evaluation of cetuximab combined with an S-1 and oxaliplatin regimen for Chinese patients with advanced gastric cancer. World J Surg Oncol 2014. [PMID: 24758484 DOI: 10.1186/1477-7819-] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open

Liu GF, Tang D, Li P, Wang S, Xu YX, Long AH, Zhou NL, Zhang LL, Chen J, Xiang XX. S-1-based combination therapy vs S-1 monotherapy in advanced gastric cancer: a meta-analysis. World J Gastroenterol 2014;20:310-318. [PMID: 24415887 PMCID: PMC3886025 DOI: 10.3748/wjg.v20.i1.310] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Revised: 10/11/2013] [Accepted: 10/17/2013] [Indexed: 02/06/2023] Open

Wu JR, Tang WZ, Chen X, Xie YT, Chen SY, Peng QL, Xie L, Deng Y, Li TJ, He Y, Wang J, Li S, Qin X. S-1-based therapy versus S-1 monotherapy in advanced gastric cancer: a meta-analysis. Tumour Biol 2014;35:3283-93. [PMID: 24390661 DOI: 10.1007/s13277-013-1429-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2013] [Accepted: 11/13/2013] [Indexed: 12/14/2022] Open