Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial

Hamaguchi, Tetsuya; Shimada, Yasuhiro; Mizusawa, Junki; Kinugasa, Yusuke; Kanemitsu, Yukihide; Ohue, Masayuki; Fujii, Satoshi; Takiguchi, Nobuhiro; Yatsuoka, Toshimasa; Takii, Yasumasa; Ojima, Hitoshi; Masuko, Hiroyuki; Kubo, Yoshiro; Mishima, Hideyuki; Yamaguchi, Takashi; Bando, Hiroyuki; Satô, Toshihiko; Kato, Takeshi; Nakamura, Kenichi; Fukuda, Haruhiko; Moriya, Yoshihiro

doi:10.1016/s2468-1253(17)30297-2

Cited by 43 publications

(39 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A means for choosing the most suitable oral FU for each patient, outside of the profile of toxicity, has been sought. A recent Japanese RCT, JCOG0910, 18 failed to demonstrate the non-inferiority of DFS of S-1 to that of capecitabine as adjuvant chemotherapy for stage III colon cancer. However, OS of the two groups was quite similar, and in the subgroup analysis, S-1 showed better DFS than capecitabine in the patient subgroup having tumours with poorly differentiated histology, 18 as shown in our study ( figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

ObjectiveAdjuvant Chemotherapy Trial of TS-1 for Colon Cancer (ACTS-CC), a randomised phase III trial, demonstrated that adjuvant therapy with S-1 for stage III colon cancer was non-inferior in 3-year disease-free survival (DFS) to that of tegafur-uracil plus leucovorin (UFT/LV). We updated DFS and overall survival (OS) and performed T x N subset analysisMethodsA total of 1518 patients with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80–120 mg/day on days 1–28 every 42 days, four courses) or UFT/LV (UFT: 300–600 mg/day and LV: 75 mg/day on days 1–28 every 35 days, five courses)ResultsThe 5-year DFS rates of the S-1 and UFT/LV group were 70.2 % and 66.9 %, respectively (HR 0.88; 95% CI 0.74 to 1.06; p=0.177), and non-inferiority of DFS was reconfirmed with a median of 63.5-month follow-up. The similarity of OS was also confirmed (HR 0.92; 95% CI 0.72 to 1.17; p=0.488); 5-year OS rates of the S-1 and UFT/LV group were 86.0 % and 84.4 %, respectively. No significant interactions were identified between the major baseline characteristics and DFS of the S-1 and UFT/LV groups, except for histological type; S-1 was more favourable in patients with poorly differentiated adenocarcinoma. Patient outcomes were well separated by TNM-substages (IIIA/IIIB/IIIC). With the patients divided into 20 subsets by T and N factors, the DFS and OS rates of T3 and N1 subset, which accounted for 62 % of stage IIIB patients and 44 % of all studied subjects, were significantly better than those of the other subsets in stage IIIB and similar to those of stage IIIA.ConclusionsAdjuvant therapy of S-1 for stage III colon cancer was reconfirmed to be non-inferior in DFS to those of UFT/LV after long follow-up. No difference in OS was also demonstrated. T3N1 patients might be considered separately from other patients included in stage IIIB because of its favourable outcome.Trial registration numberNCT00660894.

show abstract

Section: Resultsmentioning

confidence: 99%

Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Another trial determined that S-1 for stage III colon cancer is non-inferior to UFT/LV [12]. However, it remains unclear as to which oral 5-FU is the most effective, especially in older patients [13]. These findings should be interpreted with consideration to several limitations.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately one-fourth of incident colon cancer patients present with node-positive stage III disease [8]. Stage III colon cancer patients have a high risk of recurrence after undergoing curative resection, [2,3] and several randomized controlled trials (RCTs) have compared the effectiveness of various adjuvant chemotherapy regimens for these patients [9][10][11][12][13]. However, clinical studies that evaluate the effects of adjuvant chemotherapy tend to have a selection bias toward younger patients.…”

Section: Introductionmentioning

confidence: 99%

Effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age: a Japanese real-world cohort study

et al. 2020

View full text Add to dashboard Cite

Background: Adjuvant chemotherapy is relatively underused in older patients with colon cancer in Japan, and its age-specific effects on clinical outcomes remain unclear. This study aimed to assess the effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age in a Japanese real-world setting. Methods: In this multi-center retrospective cohort study, we analyzed patient-level information through a record linkage of population-based cancer registry data and administrative claims data. The study population comprised patients aged ≥18 years who received a pathological diagnosis of stage III colon cancer and underwent curative resection between 2010 and 2014 at 36 cancer care hospitals in Osaka Prefecture, Japan. Patients were divided into two groups based on age at diagnosis (< 75 and ≥ 75 years). The effect of adjuvant chemotherapy was analyzed using Cox proportional hazards regression models for all-cause mortality with inverse probability weighting of propensity scores. Adjusted hazard ratios were estimated for both age groups. Results: A total of 783 patients were analyzed; 476 (60.8%) were aged < 75 years and 307 (39.2%) were aged ≥75 years. The proportion of older patients who received adjuvant chemotherapy (36.8%) was substantially lower than that of younger patients (73.3%). In addition, the effect of adjuvant chemotherapy was different between the age groups: the adjusted hazard ratio was 0.56 (95% confidence interval: 0.33-0.94, P = 0.027) in younger patients and 1.07 (0.66-1.74, P = 0.78) in older patients. Conclusions: The clinical effectiveness of adjuvant chemotherapy in older patients with stage III colon cancer appears limited under current utilization practices.

show abstract

“…[1][2][3] In Japan, oral fluoropyrimidines such as capecitabine, tegafur-uracil and leucovorin (UFT/LV), and S-1 have been preferred because oral fluoropyrimidines alone demonstrated favorable outcomes in patients with stage III colon cancer, most of whom underwent D3 lymph node dissection (3-year disease-free survival [DFS] rate, 70.0%-82.0%), in Japanese randomized trials, and their treatment is convenient and associated with mild toxicities. [4][5][6][7] However, stage III disease includes subgroups of patients with very poor outcomes. In the ACTS-CC trial, the 3-year DFS rate in patients with stage IIIA, IIIB, and IIIC disease who received UFT/LV were 87.9%, 74.2%, and 46.4%, respectively.…”

Section: Introductionmentioning

confidence: 99%

S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized, Open-label, Multicenter, Phase III Superiority Trial

Sunami

Kusumoto

Ota

et al. 2020

Clinical Colorectal Cancer

View full text Add to dashboard Cite

To our knowledge, the ACTS-CC 02 trial is the first randomized phase III study to evaluate the therapeutic usefulness of oxaliplatin-based adjuvant chemotherapy in patients with high-risk stage III colon cancer. SOX (S-1 plus oxaliplatin) was not shown to be superior to UFT/LV (uracil-tegafur plus leucovorin) in term of disease-free survival. However, the oxaliplatin-based regimen was suggested to be more effective in advanced disease, such as N2b. Background: The efficacy of S-1 plus oxaliplatin (SOX) as postoperative adjuvant chemotherapy for colon cancer has not been established. This randomized phase III study was designed to verify the superiority of SOX over tegafur-uracil and leucovorin (UFT/LV) in patients with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin Present address of the feeding arteries). Patients and Methods: Patients who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300 mg/m 2 of UFT and 75 mg/day of LV on days 1-28, every 35 days, 5 cycles) or SOX (100 mg/m 2 of oxaliplatin on day 1 and 80 mg/m 2 of S-1 on days 1-14, every 21 days, 8 cycles). The primary endpoint was disease-free survival (DFS). Results: A total of 478 patients in the UFT/LV group and 477 patients in the SOX group were included in the primary analysis. The 3-year DFS was 60.6% (95% confidence interval [CI], 56.0%-64.9%) in the UFT/LV group and 62.7% (95% CI, 58.1%-66.9%) in the SOX group. The stratified hazard ratio for DFS was 0.90 (95% CI, 0.74-1.09; stratified log-rank test, P ¼ .2780). In the N2b subgroup, the 3-year DFS was 46.0% (95% CI, 37.5%-54.0%) in the UFT/LV group and 54.7% (95% CI, 45.7%e62.7%) in the SOX group (hazard ratio, 0.76; 95% CI, 0.55-1.05). Conclusion: As postoperative adjuvant chemotherapy, SOX was not superior to UFT/LV in terms of DFS in patients with high-risk stage III colon cancer.

show abstract

Capecitabine versus S-1 as adjuvant chemotherapy for patients with stage III colorectal cancer (JCOG0910): an open-label, non-inferiority, randomised, phase 3, multicentre trial

Cited by 43 publications

References 26 publications

Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer

Updated 5-year survival and exploratory T x N subset analyses of ACTS-CC trial: a randomised controlled trial of S-1 versus tegafur-uracil/leucovorin as adjuvant chemotherapy for stage III colon cancer

Effect of adjuvant chemotherapy on survival benefit in stage III colon cancer patients stratified by age: a Japanese real-world cohort study

S-1 and Oxaliplatin Versus Tegafur-uracil and Leucovorin as Postoperative Adjuvant Chemotherapy in Patients With High-risk Stage III Colon Cancer (ACTS-CC 02): A Randomized, Open-label, Multicenter, Phase III Superiority Trial

Contact Info

Product

Resources

About