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      Factors Influencing Clinicians' Choice of Adjuvant S-1 versus Capecitabine plus Oxaliplatin after Curative Gastrectomy in Patients with Gastric Cancer

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          Abstract

          Purpose: Two recent randomized, phase III trials in Asia (ACTS-GC and CLASSIC) documented the survival benefit of postoperative chemotherapy after D2 lymph node dissection in patients with gastric cancer. We sought to determine what factors influenced clinicians' choices of either S-1 or capecitabine plus oxaliplatin (CAPOX) as adjuvant therapy after curative D2 gastrectomy.

          Materials and Methods: We retrospectively reviewed the clinicopathologic factors and adjuvant treatments for 435 patients from nine centers in Korea who were treated with either S-1 or CAPOX adjuvant chemotherapy after undergoing curative D2 gastrectomy between January 2013 and July 2014.

          Results: Of the 435 patients, 204 (46.9%) were treated with S-1 and 231 (53.1%) were treated with CAPOX. The median age at diagnosis was 61 years (range, 30-88). CAPOX was prescribed more often for patients who were 65 years of age or younger than for patients who were age 65 or older (77.1% vs. 22.9%, P<0.0001). Of the patients in stage II, 121 (60.8%) were treated with S-1 and 78 (39.2%) were given CAPOX; however, of those in stage III, 83 (35.2%) received S-1 and 153 (64.8%) were treated with CAPOX (P<0.0001).

          Conclusions: Clinicians only preferred CAPOX for younger patients with stage III gastric cancer after curative D2 gastrectomy. However, for elderly patients, clinicians more chose S-1 regardless of the stage.

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          Most cited references3

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          Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial.

          D2 gastrectomy is recommended in US and European guidelines, and is preferred in east Asia, for patients with resectable gastric cancer. Adjuvant chemotherapy improves patient outcomes after surgery, but the benefits after a D2 resection have not been extensively investigated in large-scale trials. We investigated the effect on disease-free survival of adjuvant chemotherapy with capecitabine plus oxaliplatin after D2 gastrectomy compared with D2 gastrectomy only in patients with stage II-IIIB gastric cancer. The capecitabine and oxaliplatin adjuvant study in stomach cancer (CLASSIC) study was an open-label, parallel-group, phase 3, randomised controlled trial undertaken in 37 centres in South Korea, China, and Taiwan. Patients with stage II-IIIB gastric cancer who had had curative D2 gastrectomy were randomly assigned to receive adjuvant chemotherapy of eight 3-week cycles of oral capecitabine (1000 mg/m(2) twice daily on days 1 to 14 of each cycle) plus intravenous oxaliplatin (130 mg/m(2) on day 1 of each cycle) for 6 months or surgery only. Block randomisation was done by a central interactive computerised system, stratified by country and disease stage. Patients, and investigators giving interventions, assessing outcomes, and analysing data were not masked. The primary endpoint was 3 year disease-free survival, analysed by intention to treat. This study reports a prespecified interim efficacy analysis, after which the trial was stopped after a recommendation by the data monitoring committee. The trial is registered at ClinicalTrials.gov (NCT00411229). 1035 patients were randomised (520 to receive chemotherapy and surgery, 515 surgery only). Median follow-up was 34·2 months (25·4-41·7) in the chemotherapy and surgery group and 34·3 months (25·6-41·9) in the surgery only group. 3 year disease-free survival was 74% (95% CI 69-79) in the chemotherapy and surgery group and 59% (53-64) in the surgery only group (hazard ratio 0·56, 95% CI 0·44-0·72; p<0·0001). Grade 3 or 4 adverse events were reported in 279 of 496 patients (56%) in the chemotherapy and surgery group and in 30 of 478 patients (6%) in the surgery only group. The most common adverse events in the intervention group were nausea (n=326), neutropenia (n=300), and decreased appetite (n=294). Adjuvant capecitabine plus oxaliplatin treatment after curative D2 gastrectomy should be considered as a treatment option for patients with operable gastric cancer. F Hoffmann-La Roche and Sanofi-Aventis. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer.

            The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study. Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety. The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic. On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.
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              World Health Organization classification of tumours. Pathology and genetics of tumours of the digestive system

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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2016
                27 July 2016
                : 7
                : 12
                : 1711-1715
                Affiliations
                [1 ]Division of Hematology-Oncology, Department of Internal Medicine, Kyung Hee University Hospital at Gangdong, Seoul, South Korea
                [2 ]Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, South Korea
                [3 ]Division of Hematology-Oncology, Department of Medicine, Myongji Hospital, Goyang-si, Gyeonggido, South Korea
                [4 ]Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea
                [5 ]Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju, South Korea
                [6 ]Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea
                [7 ]Department of Internal Medicine, Dong-A University College of Medicine, Busan, South Korea
                [8 ]Division of Hematology and Oncology, Department of Internal Medicine, Hanyang University College of Medicine, Seoul, South Korea
                [9 ]Division of Hematology-Oncology, Department of Internal Medicine, Dankook University College of Medicine, Cheonan, South Korea
                [10 ]Division of Hematology-Oncology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea
                [11 ]Department of Surgery, Chung-Ang University College of Medicine, Seoul, South Korea
                Author notes
                ✉ Corresponding author: Division of Hematology/Oncology, Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, 102 Heukseok-ro, Dongjak-gu, Seoul 156-755, Republic of Korea. Tel: +82-2-6299-1403; Fax: 02-6299-1459; E-mail: hematoonco@ 123456naver.com

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav07p1711
                10.7150/jca.15598
                5039392
                92d2fd5f-1e68-436c-b491-b24c3160dee1
                © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
                History
                : 21 March 2016
                : 7 June 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                stomach neoplasms,chemotherapy,adjuvant,gastrectomy
                Oncology & Radiotherapy
                stomach neoplasms, chemotherapy, adjuvant, gastrectomy

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