Comparison of capecitabine and oxaliplatin with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy

Abstract Background The benefits of adjuvant chemotherapy for elderly patients with gastric cancer (GC) remain unknown because elderly patients are underrepresented in most clinical trials. This study aimed to evaluate the effectiveness and complications of adjuvant chemotherapy in patients > 65 years of age after laparoscopic D2 gastrectomy. Methods This was a single-center retrospective cohort study of elderly patients (> 65 years) with stage II/III GC who underwent curative laparoscopic D2 gastrectomy with R0 resection between 2004 and 2018. The adjuvant chemotherapy regimens included monotherapy (oral capecitabine) and doublet chemotherapy (oral capecitabine plus intravenous oxaliplatin [XELOX] or intravenous oxaliplatin, leucovorin, and 5-fluorouracil [FOLFOX]). The data were retrieved from a prospectively registered database maintained at the Department of General Surgery in Nanfang Hospital, China. The patients were divided as surgery alone and surgery plus adjuvant chemotherapy (chemo group). The overall survival (OS), disease-free survival (DFS), chemotherapy duration, and toxicity were examined. Results There were 270 patients included: 169 and 101 in the surgery and chemo groups, respectively. There were 10 (10/101) and six (6/101) patients with grade 3+ non-hematological and hematological adverse events. The 1−/3−/5-year OS rates of the surgery group were 72.9%/51.8%/48.3%, compared with 90.1%/66.4%/48.6% for the chemo group (log-rank test: P = 0.018). For stage III patients, the 1−/3−/5-year OS rates of the surgery group were 83.7%/40.7%/28.7%, compared with 89.9%/61.2%/43.6% for the chemo group (log-rank test: P = 0.015). Adjuvant chemotherapy was significantly associated with higher OS (HR = 0.568, 95%CI: 0.357–0.903, P = 0.017) and DFS (HR = 0.511, 95%CI: 0.322–0.811, P = 0.004) in stage III patients. Conclusions This study suggested that adjuvant chemotherapy significantly improves OS and DFS compared with surgery alone in elderly patients with stage III GC after D2 laparoscopic gastrectomy, with a tolerable adverse event profile.

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Five-Year Outcomes of a Phase II Study of Adjuvant Chemotherapy with S-1 Plus Docetaxel for Stage III Gastric Cancer After Curative D2 Gastrectomy

Annals of Oncology ◽

10.1093/annonc/mdu165.42 ◽

2014 ◽

Vol 25 ◽

pp. ii27

Author(s):

Tamura Shigeyuki ◽

Fujitani Kazumasa ◽

Kimura Yutaka ◽

Tsuji Takeshi ◽

Iijima Shohei ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Phase Ii Study ◽

Stage Iii ◽

D2 Gastrectomy

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Phase II study of adjuvant chemotherapy of S-1 plus oxaliplatin for patients with stage III gastric cancer after D2 gastrectomy

Gastric Cancer ◽

10.1007/s10120-015-0581-1 ◽

2015 ◽

Vol 20 (1) ◽

pp. 175-181 ◽

Cited By ~ 32

Author(s):

Kohei Shitara ◽

Keisho Chin ◽

Takaki Yoshikawa ◽

Hitoshi Katai ◽

Masanori Terashima ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Phase Ii Study ◽

Stage Iii ◽

D2 Gastrectomy

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Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy

Gastric Cancer ◽

10.1007/s10120-013-0273-7 ◽

2013 ◽

Vol 17 (2) ◽

pp. 348-353 ◽

Cited By ~ 16

Author(s):

Kazumasa Fujitani ◽

Shigeyuki Tamura ◽

Yutaka Kimura ◽

Takeshi Tsuji ◽

Jin Matsuyama ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Phase Ii Study ◽

Stage Iii ◽

D2 Gastrectomy

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Phase II Feasibility Study of Adjuvant S-1 Plus Docetaxel Repeated for 6 Months as Adjuvant Chemotherapy for Stage III Gastric Cancer After Curative D2 Gastrectomy (OGSG 1002)

Annals of Oncology ◽

10.1093/annonc/mdu165.41 ◽

2014 ◽

Vol 25 ◽

pp. ii27

Author(s):

Kimura Yutaka ◽

Fujitani Kazumasa ◽

Tamura Shigeyuki ◽

Matsuyama Jin ◽

Imamura Hiroshi ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Feasibility Study ◽

Phase Ii ◽

Stage Iii ◽

D2 Gastrectomy

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Three-year outcomes of two phase II studies of adjuvant chemotherapy with S-1 plus oxaliplatin or capecitabine plus oxaliplatin in patients with stage III gastric cancer after D2 gastrectomy.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.94 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 94-94 ◽

Cited By ~ 1

Author(s):

Yoshiaki Nakamura ◽

Takeharu Yamanaka ◽

Keisho Chin ◽

Haruhiko Cho ◽

Hitoshi Katai ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Pooled Analysis ◽

Stage Iii ◽

Phase Ii Trials ◽

Two Phase ◽

D2 Gastrectomy ◽

Phase Ii Studies

94 Background: Two phase II trials of oxaliplatin-based adjuvant chemotherapy for patients (pts) with gastric cancer (GC) after D2 gastrectomy have been conducted in Japan; the J-CLASSIC study of capecitabine plus oxaliplatin (CAPOX) and the SOXaGC study of S-1 plus oxaliplatin (SOX). In the current study, we evaluated survival outcomes of the two trials. Methods: The J-CLASSIC, enrolling stage II and III pts from 12 centers between July 2012 and July 2013, evaluated eight cycles of CAPOX. The SOXaGC, enrolling stage III pts from 11 centers between July 2013 and February 2014, evaluated seven cycles of SOX after one cycle of S-1 monotherapy. The two studies were conducted sequentially and most centers (9 centers) participated in both trials. In this pooled analysis, we updated relapse-free survival (RFS) and overall survival (OS) information. The median follow-up time was 49 months in the J-CLASSIC and 39 months in the SOXaGC. Results: Fifty-nine stage III pts treated with CAPOX and 62 stage III pts treated with SOX were analyzed. The 3-year RFS and OS rates of SOX were 70.9% (57.8-80.5%) and 75.7% (63.0-84.6%), respectively, whereas the 3-year RFS and OS rates of CAPOX were 67.8% (54.3-78.1%) and 79.3% (66.5-87.7%), respectively. The hazard ratio (HR) of SOX in comparison to CAPOX was 0.925 (0.498-1.720) for RFS, suggesting the efficacy of the two treatments was similar. Trend of a different efficacy was observed in some particular subgroups; the HR for RFS was 1.732 (0.506-5.927) in the intestinal type and 0.735 (0.353-1.528) in the diffuse type, while that was 2.008 (0.447-9.016) in stage IIIA, 0.872 (0.266-2.857) in stage IIIB, and 0.597 (0.258-1.383) in stage IIIC. Conclusions: This is the first report of survival follow-up in Japanese GC pts with oxaliplatin-based adjuvant chemotherapy, which suggests comparable outcomes in both treatments for stage III GC. Different trend in the treatment effect by histologic type or stage warrants further evaluation in a larger cohort. Clinical trial information: UMIN000026883.

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Five-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy (OGSG1002)

Gastric Cancer ◽

10.1007/s10120-019-01023-w ◽

2019 ◽

Vol 23 (3) ◽

pp. 520-530 ◽

Cited By ~ 4

Author(s):

Kazumasa Fujitani ◽

◽

Shigeyuki Tamura ◽

Yutaka Kimura ◽

Jin Matsuyama ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Phase Ii Study ◽

Stage Iii ◽

D2 Gastrectomy

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Phase II feasibility study of adjuvant S-1 plus docetaxel for stage III gastric cancer patients after curative D2 gastrectomy (OGSG 0604)

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.e15567 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. e15567-e15567

Author(s):

K. Fujitani ◽

S. Tamura ◽

Y. Kimura ◽

T. Tsuji ◽

J. Matsuyama ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Performance Status ◽

Progression Free Survival ◽

Phase Iii ◽

Stage Iii ◽

R0 Resection ◽

D2 Gastrectomy ◽

Grade 3

e15567 Background: Although an adjuvant chemotherapy with S-1 has become the standard treatment for stage II-III gastric cancer (GC) patients (pts) after curative D2 gastrectomy in Japan, the survival benefit for stage III pts obtained by S-1 is considered to be modest. S-1 plus docetaxel has shown a good response rate of 56% with prolonged median overall survival (OS) of 14.3 months in pts with advanced GC. This phase II study evaluated the feasibility and safety of adjuvant S-1 plus docetaxel for stage III GC pts after R0 resection. Methods: Patients with curatively resected pathological stage III GC receiving D2 dissection, age 20–80 years, performance status < 1, no prior adjuvant treatment, adequate organ function, and informed consent were given S-1 (80 mg/m2/day) orally for consecutive 2 weeks plus docetaxel (40 mg/m2) intravenously on day 1, repeated every 3 weeks. The treatment was started within 45 days after gastrectomy, and repeated for 4 cycles, followed by S-1 monotherapy until 1 year after surgery. Study endpoints included feasibility of the 4 cycles of S-1 plus docetaxel as primary, and safety, progression free survival (PFS), and OS as secondary. Sample size was set to be 50, which was determined to reject the feasibility of 50% under the expectation of 75% with power of 90% and two-sided α of 5%. Results: Fifty-three pts, 42 males and 11 females with a median age of 65 years, were enrolled between 5/2007 and 8/2008. Pathological stages included IIIA in 36 pts and IIIB in 17 pts. Planned 4 cycles of treatment were delivered to 41 out of 53 pts, with the feasibility of 77.4% (95% CI 63.8–87.7%, P<0.001). Reasons for discontinuation were recurrent cancer in 1 pt, adverse events in 10, and miscellaneous in 1, respectively. Grade 4 neutropenia was observed in 28% of pts with grade 3 febrile neutropenia in 9%. Non-hematological toxicities of grade 3 or more involved fatigue in 6%, anorexia in 9%, and nausea in 6%. No treatment-related deaths occurred. Conclusions: Adjuvant S-1 plus docetaxel was well-tolerated and showed good compliance. Although follow-up is ongoing on survival, this regimen could be a candidate of future phase III trial seeking for the optimal adjuvant chemotherapy for stage III GC pts after curative D2 gastrectomy. No significant financial relationships to disclose.

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Three-year outcomes of a phase II study of adjuvant chemotherapy with S-1 plus docetaxel for stage III gastric cancer after curative D2 gastrectomy (OGSG1002)

Annals of Oncology ◽

10.1093/annonc/mdx261.086 ◽

2017 ◽

Vol 28 ◽

pp. iii37 ◽

Cited By ~ 2

Author(s):

Ryohei Kawabata ◽

Kazumasa Fujitani ◽

Shigeyuki Tamura ◽

Yutaka Kimura ◽

Hiroshi Imamura ◽

...

Keyword(s):

Gastric Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Phase Ii Study ◽

Stage Iii ◽

D2 Gastrectomy

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Adjuvant albumin-bound paclitaxel combined with S-1 vs. oxaliplatin combined with capecitabine after D2 gastrectomy in patients with stage III gastric adenocarcinoma: a phase III multicenter, open-label, randomized controlled clinical trial protocol

BMC Cancer ◽

10.1186/s12885-020-07772-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Xiangdong Cheng ◽

Dan Wu ◽

Nong Xu ◽

Luchuan Chen ◽

Zhilong Yan ◽

...

Keyword(s):

Gastric Cancer ◽

Clinical Trial ◽

Overall Survival ◽

Clinical Study ◽

Adjuvant Chemotherapy ◽

Locally Advanced ◽

Phase Iii ◽

Stage Iii ◽

Open Label ◽

D2 Gastrectomy

Abstract Background Surgery is the only treatment option for operable gastric cancer. The CLASSIC and ACTS-GC studies showed that the 5-year overall survival (OS) of patients with stage III gastric cancer undergoing D2 gastrectomy is still very low. Whether adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) combined chemotherapy is more effective than the XELOX standard adjuvant chemotherapy in patients with stage III gastric cancer has not been confirmed. Methods This is a multicenter, open-label, phase III clinical study. In this trial, 616 patients with locally advanced stage III gastric cancer that underwent curative D2 radical surgery and achieved R0 are planned to be included. Patients will be randomized 1:1 to nab-paclitaxel combined with S-1 (AS) vs. oxaliplatin combined with capecitabine (XELOX). XELOX group: Patients assigned to the XELOX group received eight 3-week cycles of oral capecitabine (1000 mg/m2) twice daily on days 1–14 of each cycle plus intravenous oxaliplatin 130 mg/m2 on day 1 of each cycle. AS group: AS group received eight 3-week cycles of oral S-1 (80–120 mg) (< 1.25 m2, 40 mg; 1.25 to < 1.5 m2, 50 mg; and > 1.5 m2, 60 mg) twice daily on days 1–14 plus intravenous nab-paclitaxel 120 mg/m2 on days 1 and 8 of each cycle. The primary endpoint was the 3-year disease-free survival (3-year-DFS) defined as the time from randomisation to the time of recurrence of the original gastric cancer, development of a new gastric cancer, or death from any cause. The secondary endpoints were the overall survival, (defined as the time from the date of randomisation to date of death from any cause) and safety (any adverse event). Discussion Compared with previous studies, this study includes nab-paclitaxel based on S-1 adjuvant chemotherapy, which is expected to achieve better efficacy and lower toxicity than the standard treatment. This study is the first clinical study to evaluate the safety and efficacy of nab-paclitaxel combined with S-1 in patients with stage III gastric cancer after D2 radical resection. Trial registration This clinical trial has been registered with ClinicalTrials.gov, registration number: NCT04135781, on October 20th, 2019.

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