Trial Outcomes & Findings for Docetaxel+Oxaliplatin+S-1 (DOS) Regimen as Neoadjuvant Chemotherapy in Advanced Gastric Cancer (NCT NCT01515748)

Last Updated: 2023-12-13

Results Overview

PFS was defined as the time from randomization to objective tumor progression, or recurrence or death. Progressive disease (PD) was defined as follows: 1) In Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) Arm, PD was determined according to the RECIST 1.1 Criteria during the neo-adjuvant chemotherapy period; 2) Irrespective of curative resection, if an intraoperative distant metastasis was observed or a distant metastasis was reported from pathology, it was considered PD; 3) If residual cancer cells were visually identified at the resection margin during surgery but could not be completely resected (R2), it was considered PD; 4) If residual cancer cells were finally confirmed at the resection margin during postoperative histology (R1), it was considered PD; 5) In case of finding a recurrence/distant metastasis or a new lesion during follow-up after R0 complete resection, it was defined as the first tumor assessment date when it was observed.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

530 participants

Primary outcome timeframe

3 years

Results posted on

2023-12-13

Participant Flow

The study was conducted at 18 sites in Korea. A total of 693 participants were screened between 30 December 2011 to 02 January 2019, of which, 163 were screen failures. Screen failures were mainly due to inclusion criteria not met.

Total of 530 participants were enrolled and randomized in study. Assignment was done using Interactive Web-Response System (IWRS) in 1:1 to treatment arms. Randomization was stratified by site and Tumor size, Lymph Nodes affected, Metastases (TNM) \[T2/N+,T3-4/N+,T4/N-\] stage.

Participant milestones

Participant milestones
Measure	Surgery + Adjuvant Chemotherapy (SC) Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 milligrams per square meter (mg/m\^2) administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after End-of-Treatment (EOT) until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 intravenously (IV) for greater than or equal to (\>=)1 hour (hr) on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Overall Study STARTED	264	266
Overall Study Treated	195	241
Overall Study COMPLETED	225	211
Overall Study NOT COMPLETED	39	55

Reasons for withdrawal

Reasons for withdrawal
Measure	Surgery + Adjuvant Chemotherapy (SC) Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 milligrams per square meter (mg/m\^2) administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after End-of-Treatment (EOT) until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 intravenously (IV) for greater than or equal to (\>=)1 hour (hr) on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Overall Study Withdrawal by Subject	32	41
Overall Study Lost to Follow-up	2	4
Overall Study Other than specified above	5	10

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Surgery + Adjuvant Chemotherapy (SC) n=264 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=266 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Total n=530 Participants Total of all reporting groups
Age, Continuous	57.28 years STANDARD_DEVIATION 10.09 • n=264 Participants	57.11 years STANDARD_DEVIATION 10.03 • n=266 Participants	57.19 years STANDARD_DEVIATION 10.05 • n=530 Participants
Sex: Female, Male Female	50 Participants n=264 Participants	59 Participants n=266 Participants	109 Participants n=530 Participants
Sex: Female, Male Male	214 Participants n=264 Participants	207 Participants n=266 Participants	421 Participants n=530 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.

PRIMARY outcome

Timeframe: 3 years

Population: Full Analysis Set (FAS): included all randomized participants who satisfied inclusion/exclusion criteria and had at least one tumor assessment after baseline visit (Day 0). The CSC Arm included all participants exposed to at least one dose of Docetaxel+Oxaliplatin+S-1 investigational products. The SC Arm included all participants who had surgery.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=246 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=233 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Percentage of Participants With 3-Year Progression-Free Survival (PFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1	60.24 percentage of participants Interval 53.55 to 66.28	66.82 percentage of participants Interval 60.13 to 72.65

SECONDARY outcome

Timeframe: From randomization to date of death due to any cause (maximum duration: up to 10 years)

Population: Analysis was performed on FAS population.

OS was defined as the time from randomization to death due to any cause. Analyzed using Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=246 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=233 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Overall Survival (OS)	NA months Median and upper and lower limit of confidence interval could not be calculated because of less number of participants reaching the OS event i.e., few participants died.	NA months Median and upper and lower limit of confidence interval could not be calculated because of less number of participants reaching the OS event i.e., few participants died.

SECONDARY outcome

Timeframe: Up to 10 years

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

TNM pathological stage was determined according to standardized histopathology and the American Joint Committee on Cancer (AJCC) staging system 7th Edition (Stages 0,IA,IB,IIA,IIB,IIIA,IIIB,IIIC and IV). Stage 0=carcinoma in situ with no metastatic potential; Stage IA=T1N0M0; Stage IB=T2N0M0,T1N1M0; Stage IIA=T3N0M0,T2N1M0,T1N2M0;Stage IIB=T4aN0M0,T3N1M0,T2N2M0,T1N3M0;Stage IIIA=T4aN1M0,T3N2M0,T2N3M0;Stage IIIB=T4bN0-1M0,T4aN2M0,T3N3M0;Stage IIIC=T4bN2-3M0, T4aN3M0 and Stage IV= distant metastases (M1) at diagnosis; where "T" denotes "tumor size" where T1: tumor invades lamina propria, muscularis mucosae, or submucosa; T2: invades muscularis propria; T3: invasion of subserosa; T4: T4a: penetrate serosa (visceral peritoneum) T4b: invade adjacent tissue and " N" denotes "nodes affected" where N1:1-2 positive lymph nodes; N2:3-6 positive lymph nodes; N3: 7 or more positive lymph nodes and "M" denotes metastases where M0: no distant metastases. Higher stages indicates worse outcome.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=246 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=222 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Number of Participants With Post-Operative Pathological Stage Response Stage 0	0 Participants	23 Participants
Number of Participants With Post-Operative Pathological Stage Response Stage IA	9 Participants	32 Participants
Number of Participants With Post-Operative Pathological Stage Response Stage IB	18 Participants	23 Participants
Number of Participants With Post-Operative Pathological Stage Response Stage IIA	30 Participants	47 Participants
Number of Participants With Post-Operative Pathological Stage Response Stage IIB	25 Participants	36 Participants
Number of Participants With Post-Operative Pathological Stage Response Stage IIIA	35 Participants	18 Participants
Number of Participants With Post-Operative Pathological Stage Response Stage IIIB	49 Participants	24 Participants
Number of Participants With Post-Operative Pathological Stage Response Stage IIIC	46 Participants	14 Participants
Number of Participants With Post-Operative Pathological Stage Response Stage IV	34 Participants	5 Participants

SECONDARY outcome

Timeframe: Up to 10 years

Population: Analysis was performed on FAS population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Tumor condition was explained according to the Residual Tumor (R) Classification: R0; No residual cancer (negative cross-section), R1; Microscopically observed residual cancer (positive cross-section), R2; Macroscopically observed residual cancer.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=246 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=222 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Percentage of Participants With R0 Resection	83.74 percentage of participants Interval 79.13 to 88.35	95.50 percentage of participants Interval 92.77 to 98.22

SECONDARY outcome

Timeframe: From randomization up to 30 days after last dose of study drug (maximum duration: up to 10 years)

Population: Analysis was performed on safety population which included participants who were administered at least one dose of the investigational product.

TEAEs were defined as adverse events (AE) that appeared or worsened during the treatment period (up to 30 days after the last dose of the investigational product). SAE was an AE or adverse drug reaction at any dose of the investigational product that corresponded to one of the following: resulting in death or is life threatening; requiring in-patient hospitalization or prolongation of existing hospitalization; resulting in persistent or significant disability of dysfunction; resulting in congenital anomaly or birth defect; important medical event.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=195 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=241 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any treatment emergent SAE	57 Participants	102 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAE	190 Participants	237 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs leading to permanent discontinuation	11 Participants	25 Participants

SECONDARY outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)

Population: Analysis was performed on safety population.

NCI-CTCAE version 4.03 was used to determine Grade(Gr),where Gr refers to severity of AE:Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate;minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Hemoglobin(Hb)(Anemia) were based on Gr1:\<lower limit of normal (LLN)-10.0g/dL; Gr2:\<10.0-8.0g/dL; Gr3:\<8.0g/dL; Gr4:life-threatening consequences;Gr5:death. Hb increased:Gr 1:increase(incr.) in \>0-2g/dL above upper limit of normal(ULN);Gr2: incr. in \>2-4g/dL above ULN; Gr3:incr. in \>4gm/dL above ULN. White blood cell (WBC) decreased: Gr1:\<LLN - 3000/mm\^3;Gr2: \<3000-2000/mm\^3; Gr3:\<2000-1000/mm\^3;Gr4:\<1000/mm\^3. WBC (Leukocytosis):Gr3:\>100,000/mm\^3, Gr4:clinical manifestations of leucostasis;Gr5:Death. Abnormal Neutrophil count (ANC):- Gr1:\<LLN-1500/mm\^3;Gr2:\<1500-1000/mm\^3; Gr3: \<1000-500/mm\^3; Gr4:\<500/mm\^3. Platelet count decreased: Gr1:\<LLN-75,000/mm\^3;Gr2:\<75,000-50,000/mm\^3;Gr3:\<50,000-25,000/mm\^3;Gr4:\<25,000/mm\^3.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=195 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=241 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb(Anemia) Gr 0 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb(Anemia) Gr 1 at Baseline to Gr >=3	0 Participants	4 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb(Anemia) Gr 2 at Baseline to Gr >=3	1 Participants	1 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb(Anemia) Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb(Anemia) Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb(Anemia) Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb increased Gr 0 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb increased Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb increased Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb increased Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb increased Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Hb increased Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC decreased Gr 0 at Baseline to Gr >=3	1 Participants	8 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC decreased Gr 1 at Baseline to Gr >=3	0 Participants	1 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC decreased Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC decreased Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC decreased Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC decreased Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC (Leukocytosis) Gr 0 at Baseline to Gr >=3	0 Participants	1 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC (Leukocytosis) Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC (Leukocytosis) Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC (Leukocytosis) Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC (Leukocytosis) Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 WBC (Leukocytosis) Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 ANC Gr 0 at Baseline to Gr >=3	14 Participants	40 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 ANC Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 ANC Gr 2 at Baseline to Gr >=3	1 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 ANC Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 ANC Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 ANC Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Platelet count decreased Gr0 at Baseline to Gr >=3	0 Participants	5 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Platelet count decreased Gr1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Platelet count decreased Gr2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Platelet count decreased Gr3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Platelet count decreased Gr4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Hematology) From Baseline Grade to Worst National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Grade >=3 Platelet count decreased Gr5 at Baseline to Gr >=3	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)

Population: Analysis was performed on safety population.

NCI-CTCAE version 4.03 was used to determine Gr,where Gr refers to severity of AE: Gr 1: mild; asymptomatic/mild symptoms; Gr 2: moderate; minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Sodium (Hyponatremia) were based on Gr1: \<LLN-130 mmol/L; Gr3: \<130-120 mmol/L; Gr4: \<120 mmol/L; life-threatening consequences; Gr5: death. Sodium (Hypernatremia):Gr 1: \>ULN-150 mmol/L; Gr2: \>150-155 mmol/L; Gr3:\>155-160 mmol/L;hospitalization; Gr4: \>160 mmol/L; life-threatening consequences; Gr5: Death. Potassium (Hypokalemia): Gr 1: \<LLN-3.0 mmol/L; Gr2: \<LLN-3.0 mmol/L; symptomatic; intervention indicated; Gr3: \<3.0-2.5 mmol/L; hospitalization indicated; Gr4: \<2.5 mmol/L; life-threatening consequences; Gr5: Death; Potassium(Hyperkalemia): Gr 1: \>ULN-5.5 mmol/L; Gr2: \>5.5-6.0 mmol/L; Gr3: \>6.0-7.0 mmol/L; hospitalization indicated; Gr4: \>7.0 mmol/L; life-threatening consequences; Gr5: Death.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=195 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=241 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyponatremia Gr 0 at Baseline to Gr >=3	1 Participants	7 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyponatremia Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyponatremia Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyponatremia Gr 3 at Baseline to Gr >=3	0 Participants	1 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyponatremia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyponatremia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypernatremia Gr 0 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypernatremia Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypernatremia Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypernatremia Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypernatremia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypernatremia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypokalemia Gr 0 at Baseline to Gr >=3	1 Participants	2 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypokalemia Gr 1 at Baseline to Gr >=3	1 Participants	1 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypokalemia Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypokalemia Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypokalemia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypokalemia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperkalemia Gr 0 at Baseline to Gr >=3	1 Participants	4 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperkalemia Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperkalemia Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperkalemia Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperkalemia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Sodium and Potassium Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperkalemia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)

Population: Analysis was performed on safety population.

NCI-CTCAE version 4.03 was used to determine Gr,where Gr refers to severity of AE:Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate;minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Calcium(Hypocalcemia) were based on Gr1: Corrected serum calcium of \<LLN-8.0 mg/dL; Gr2: Corrected serum calcium of \<8.0-7.0 mg/dL; Gr3: Corrected serum calcium of \<7.0-6.0 mg/dL ; Gr4: Corrected serum calcium of \<6.0 mg/dL;Gr5:death. Calcium(Hypercalcemia):Gr 1: Corrected serum calcium of \>ULN -11.5 mg/dL; Gr2: Corrected serum calcium of \>11.5-12.5 mg/dL; Gr3: Corrected serum calcium of \>12.5-13.5 mg/dL; Gr4: Corrected serum calcium of \>13.5 mg/dL;Gr5:Death. Creatinine increased: Gr 1: \>1-1.5\*baseline; \>ULN-1.5\*ULN; Gr2: \>1.5-3.0\*baseline; \>1.5-3.0\*ULN; Gr3: \>3.0 baseline; \>3.0-6.0\*ULN; Gr4: \>6.0 x ULN. Albumin(Hypoalbuminemia): Gr 1: \<LLN-3 g/dL; Gr2: \<3-2 g/dL; Gr3: \<2 g/dL; Gr4:life-threatening consequences;Gr5:Death.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=195 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=241 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypocalcemia Gr 0 at Baseline to Gr >=3	1 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypocalcemia Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypocalcemia Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypocalcemia Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypocalcemia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypocalcemia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypercalcemia Gr 0 at Baseline to Gr >=3	1 Participants	1 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypercalcemia Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypercalcemia Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypercalcemia Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypercalcemia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypercalcemia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine increased Gr 0 at Baseline to Gr >=3	4 Participants	8 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine increased Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine increased Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine increased Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine increased Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine increased Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoalbuminemia Gr 0 at Baseline to Gr >=3	1 Participants	2 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoalbuminemia Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoalbuminemia Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoalbuminemia Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoalbuminemia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Calcium, Creatinine and Albumin Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoalbuminemia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)

Population: Analysis was performed on safety population.

NCI-CTCAE version 4.03 was used to determine Gr, where Gr refers to severity of AE: Gr 1:mild; asymptomatic/mild symptoms; Gr 2:moderate; minimal; Gr 3:severe/medically significant; Gr 4:life-threatening consequences, Gr 5:death related to AE. Abnormal values for Aspartate and alanine aminotransferase increased were based on Gr1: \>ULN-3.0\*ULN; Gr2: \>3.0-5.0\*ULN; Gr3: \>5.0-20.0\*ULN; Gr4: \>20.0\*ULN. Blood bilirubin increased: Gr1: \>ULN-1.5\*ULN; Gr2 \>1.5-3.0\*ULN; Gr3: \>3.0-10.0\*ULN; Gr4: \>10.0\*ULN. Alkaline phosphatase increased: Gr1: \>ULN-2.5\*ULN; Gr2: \>2.5-5.0\*ULN; Gr3: \>5.0-20.0\*ULN; Gr4: \>20.0\*ULN. Glucose (Hypoglycemia): Gr 1: \<LLN-55 mg/dL; Gr2: \<55-40 mg/dL;Gr3: \<40-30 mg/dL; Gr4: \<30 mg/dL; Gr5:Death. Glucose (Hyperglycemia): Gr 1: Fasting glucose value \>ULN-160 mg/dL; Gr2: Fasting glucose value \>160-250 mg/dL; Gr3: \>250-500 mg/dL; Gr4: \>500 mg/dL; Gr5: Death.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=195 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) n=241 Participants Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Aspartate aminotransferase Gr0 at Baseline toGr>=3	1 Participants	1 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Aspartate aminotransferase Gr1 at Baseline toGr>=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Aspartate aminotransferase Gr2 at Baseline toGr>=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Aspartate aminotransferase Gr3 at Baseline toGr>=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Aspartate aminotransferase Gr4 at Baseline toGr>=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Aspartate aminotransferase Gr5 at Baseline toGr>=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alanine aminotransferase Gr0 at Baseline to Gr >=3	0 Participants	1 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alanine aminotransferase Gr1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alanine aminotransferase Gr2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alanine aminotransferase Gr3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alanine aminotransferase Gr4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alanine aminotransferase Gr5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Bilirubin increased Gr 0 at Baseline to Gr >=3	2 Participants	4 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Bilirubin increased Gr 1 at Baseline to Gr >=3	1 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Bilirubin increased Gr 2 at Baseline to Gr >=3	1 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Bilirubin increased Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Bilirubin increased Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Bilirubin increased Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alkaline phosphatase Gr 0 at Baseline to Gr >=3	3 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alkaline phosphatase Gr 1 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alkaline phosphatase Gr 2 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alkaline phosphatase Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alkaline phosphatase Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Alkaline phosphatase Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoglycemia Gr 0 at Baseline to Gr >=3	4 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoglycemia Gr 1 at Baseline to Gr >=3	1 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoglycemia Gr 2 at Baseline to Gr >=3	1 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoglycemia Gr 3 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoglycemia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hypoglycemia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperglycemia Gr 0 at Baseline to Gr >=3	4 Participants	12 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperglycemia Gr 1 at Baseline to Gr >=3	13 Participants	13 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperglycemia Gr 2 at Baseline to Gr >=3	2 Participants	10 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperglycemia Gr 3 at Baseline to Gr >=3	3 Participants	2 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperglycemia Gr 4 at Baseline to Gr >=3	0 Participants	0 Participants
Number of Participants With Shift of Laboratory Parameters (Aspartate Aminotransferase, Alanine Aminotransferase,Blood Bilirubin,Alkaline Phosphatase and Glucose Levels) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Hyperglycemia Gr 5 at Baseline to Gr >=3	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From Baseline up to 30 days after last dose of study drug (maximum duration: up to 10 years)

Population: Analysis was performed on safety population. Data was planned to be collected and analyzed for Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) arm only.

Outcome measures

Outcome measures
Measure	Surgery + Adjuvant Chemotherapy (SC) n=241 Participants Participants underwent surgery within 2 weeks after randomization followed by adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).	Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC) Participants received neo-adjuvant chemotherapy with Docetaxel 50 mg/m\^2 IV for \>= 1 hr on Day 1 of each treatment cycle plus Oxaliplatin 100 mg/m\^2 IV for \>=2 hr on Day 1 of each treatment cycle plus S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily from Day 1 to 14, of each treatment cycle followed by surgery approximately 1-3 weeks after completion of neo-adjuvant chemotherapy and adjuvant chemotherapy with S-1 \[(Gimeracil) + Oxo (Oteracil)\] 40 mg/m\^2 administered orally twice daily, from Day 1 to 28 of each cycle for 1 year, and were followed-up after EOT until disease progression or death or study cut-off date, whichever comes first (maximum duration: up to 10 years).
Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine Clearance Gr 0 at Baseline to Gr >=3	0 Participants	—
Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine Clearance Gr 1 at Baseline to Gr >=3	0 Participants	—
Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine Clearance Gr 2 at Baseline to Gr >=3	0 Participants	—
Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine Clearance Gr 3 at Baseline to Gr >=3	0 Participants	—
Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine Clearance Gr 4 at Baseline to Gr >=3	0 Participants	—
Number of Participants With Shift of Laboratory Parameters (Creatinine Clearance [Chronic Kidney Disease]) From Baseline Grade to Worst NCI-CTCAE Grade >=3 Creatinine Clearance Gr 5 at Baseline to Gr >=3	0 Participants	—

Adverse Events

Surgery + Adjuvant Chemotherapy (SC)

Serious events: 57 serious events

Other events: 141 other events

Deaths: 91 deaths

Neoadjuvant Chemotherapy +Surgery +Adjuvant Chemotherapy (CSC)

Serious events: 102 serious events

Other events: 201 other events

Deaths: 78 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER