A randomized 2X2 phase II trial comparing two and four courses of S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) as neoadjuvant chemotherapy for locally resectable advanced gastric cancer: Survival results of COMPASS.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 111-111
Author(s):  
Takaki Yoshikawa ◽  
Kazuaki Tanabe ◽  
Kazuhiro Nishikawa ◽  
Kazumasa Fujitani ◽  
Yuichi Ito ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Cancer Survival ◽  
Phase Ii Trial ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Curative Intent ◽  
Grade 3

111 Background: The prognosis for stage III gastric cancer is not satisfactory even by S-1 adjuvant chemotherapy. Neoadjuvant chemotherapy is a promising approach but its optimal duration and regimen have not been established yet. Methods: We conducted a randomized phase II trial to compare two or four courses and regimen of SC or PC using a two-by-two factorial design.Key eligibility criteria was (i) T2-3/N+ or T4aN0 in case of schirrhous or junctional tumors, T2-3 with N+ to the major branched artery, T4aN+, T4b, para-aortic nodal metastases, or resectable minimal peritoneal metastases confirmed by laparoscopy and (ii) no other distant metastasis. Patients received S-1 (80 mg/m2 for 21 days with 1 week rest) / cisplatin (60 mg/m2 at day 8) or paclitaxel / cisplatin (80 mg/m2 and 25 mg/m2, respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. Then, patients received D2 gastrectomy with curative intent. The primary endpoint was 3-year overall survival. The planned sample size was 80 eligible patients in total so that the treatment group with the superior observed 3-year OS rate by 10% increase was to be selected with a probability of 88% or higher. Results: Eighty-three patients were assigned to SC (n=41, two courses in 21 and four courses in 20) and PC (n=42, two courses in 21 and four courses in 21). Pathological response rate was 42% (17/41) in SC and 33% (14/42) in PC, and 36% (15/42) in the two courses and 39% (16/41) in the four courses. Pathological CR was 0% (0/42) in the two courses and 10% (4/41) in the four courses. Grade 3/4 adverse events by chemotherapy and grade 3/4 surgical morbidities defined by Clavien-Dindo classification were both less than 10% in each arm without treatment-related death. The 3-year OS was 60.9% (95% CI, 44.3-73.9%) in SC and 64.3% (95% CI, 47.9-76.7%) in PC, and 64.3% (95% CI, 47.9-76.7%) in the two courses and 61.0% (95% CI, 44.4-74.0%) in the four courses. Conclusions: Two courses of SC as neoadjuvant chemotherapy is recommended for a test arm of future phase III study for patients with locally resectable advanced gastric cancer. Clinical trial information: UMIN000002595.

Primary results of a randomized two-by-two factorial phase II trial comparing neoadjuvant chemotherapy with two and four courses of cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) as neoadjuvant chemotherapy for locally advanced gastric cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 93-93 ◽  
Author(s):  
Takaki Yoshikawa ◽  
Kentaro Sakamaki ◽  
Kazuhiro Nishikawa ◽  
Kazumasa Fujitani ◽  
Kazuaki Tanabe ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Control Group ◽  
Locally Advanced Gastric Cancer

93 Background: Neoadjuvant chemotherapy is promising to improve the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both active for metastatic gastric cancer. Methods: We conducted a randomized phase II trial to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and docetaxel/cisplatin/S-1 (DCS) using a two-by-two factorial design for locally resectable advanced gastric cancer. Patients with M0 and either T4 or T3 in case of junctional cancer or schirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as neoadjuvant chemotherapy. Then, patients underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was 3-year overall survival. The planned sample size was 120 eligible patients in total so that the treatment group with the superior observed 3-year OS rate by more than 60% as compared with 50% of the control group was to be selected with a probability of 85% or higher. Results: Between October 2011 and September 2014, 132 patients were assigned to CS (n = 66; 33 in 2-courses and 33 in 4-courses) and DCS (n = 66; 33 in 2-courses and 33 in 4-courses). The 3-year OS was 58.1% (95% CI, 45.8-70.3%) in CS and 60.0% (95% CI, 48.0-71.9%) in DCS with hazard ratio of 0796 (95% CI, 0.475-1.335), while that was 53.1% (95% CI, 40.9-65.4%) in the two courses and 65.0% (95% CI, 53.2-76.8%) in the four courses with hazard ratio of 0.722 (95% CI, 0.429-1.216). In the survival analysis by duration in each regimen, the 3-year OS was 58.1% (95% CI, 45.8-70.3%) both for two and four courses in CS, while that was 48.5% (95% CI, 31.4-65.5%) for two courses of DCS and was 71.9% (95% CI, 56.3-87.5%) for four courses of DCS. Conclusions: Considering high 3-year OS, four courses DCS has a value to be tested in a future phase III study to confirm superiority of neoadjuvant chemotherapy for locally advanced gastric cancer. Clinical trial information: UMIN000006378.

Irinotecan plus S-1 (IRIS) versus S-1 alone as first line treatment for advanced gastric cancer: Preliminary results of a randomized phase III study (GC0301/TOP-002)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4525-4525 ◽  
Author(s):  
K. Chin ◽  
H. Iishi ◽  
H. Imamura ◽  
O. Kobayashi ◽  
H. Imamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Cancer Survival ◽  
Single Agent ◽  
Rest Period ◽  
Phase Iii ◽  
Best Response ◽  
Independent Review ◽  
Grade 3 ◽  
Gastric Cancer Patients

4525 Background: Irinotecan has single agent activity and combination activity with S-1 reportedly in phase I/II studies with advanced gastric cancer patients (pts). S-1, oral fluoropyrimidine, also has activity on gastric cancer. A multicenter, randomized phase III trial comparing IRIS to S-1 alone in advanced gastric cancer was conducted. Methods: Pts with previously untreated gastric cancer were randomized to Arm A (oral S-1 80 mg/m2/day from day 1 to 28 followed by a 14-day rest period), or Arm B (oral S-1 80 mg/m2/day from day 1 to 21 and intravenous irinotecan 80 mg/m2 on days 1 and 15 followed by a 14-day rest). Treatment was continued unless disease progression was observed. Inclusion criteria: PS (ECOG) of 0 to 2; adequate major organ functions. Primary endpoint was overall survival. Results: From June 2004 to November 2005, 326 pts were randomized to arm A (162 pts) and arm B (164 pts). Pts characteristics (arm A vs. arm B) were as follows: median age: 63 vs. 63 years, PS 0–1: 97% vs. 97%, and distribution of subtype of intestinal/diffuse/others: 44%/55%/1% vs. 41%/58%/1%. Among 187 RECIST-evaluable pts (93 vs 94) reviewed by independent review panel, best response rates were 26.9% for arm A and 41.5% for arm B(p=0.035). Among 319 toxicity-evaluable patients (161 vs 158), grade 3 or 4 toxicities for arm A vs arm B (% of pts) were as follows: neutropenia 9.3% vs 26.6%, diarrhea 5.6% vs 15.8%, anorexia 9.9% vs 15.8%, nausea 3.7% vs 7.0%, vomiting 0.6% vs 2.5%. Conclusions: IRIS is effective, and well tolerated in pts with advanced gastric cancer. Survival analysis is underway. No significant financial relationships to disclose.

A single-arm, phase II feasibility study of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in potentially resectable gastric or gastroesophageal junction adenocarcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 96-96
Author(s):  
M. Ryu ◽  
Y. Choi ◽  
B. Kim ◽  
Y. Park ◽  
H. Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Residual Disease ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Phase Iii ◽  
R0 Resection ◽  
Locally Advanced Gastric Cancer ◽  
Grade 3

96 Background: The aim of this study was to evaluate feasibility and safety of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy in patients with potentially resectable adenocarcinoma of stomach or gastroesophageal junction. Methods: Forty-one patients with clinical stage T3-4N0M0 or T2-4N+M0 determined by CT, endoscopic ultrasonography, and laparoscopy were enrolled between DEC 2008 and MAR 2010. Gastrectomy with D2 lymph node dissection was conducted after 3 cycles of DOS chemotherapy. DOS chemotherapy consists of docetaxel 50 mg/m2 iv (day1), oxaliplatin 100 mg/m2 iv (day1), and S-1 40 mg/m2 po bid (days1-14) at 3 weeks interval. After curative gastrectomy, the patients were given 1 year of adjuvant chemotherapy with S-1 (40 mg/m2 D1-28, every 6 weeks). Results: All patients finished the planned neoadjuvant chemotherapy. Twenty-three (56%) patients achieved a partial response, and the remaining 18 patients had stable disease by CT scan after 3 cycles of DOS chemotherapy. No disease progression was observed during the neoadjuvant chemotherapy. A median 4.7 weeks (range, 4.0-7.6) after the start of the 3rd cycle of DOS chemotherapy, 39 (95%) patients underwent R0 resection with no pathologic residual disease in 4 (10%) patients. Hematologic toxicities were common including grade 4 neutropenia (32%), grade 3 thrombocytopenia (17%), and febrile neutropenia (10%). However, hematologic toxicities were generally transient and manageable. There were no grade 3 or 4 non-hematologic toxicities with frequency > 5% of patients. With all toxicities taken together, 21 (51%) patients experienced grade 3 or 4 toxicities (except grade 3 neutropenia). There was no treatment-related death, and surgical complications included only mild wound problem in 4 (10%) patients. Conclusions: In this study, neoadjuvant DOS chemotherapy could induce a sufficient down-staging and R0 resection of locally advanced gastric cancer with mild and manageable toxicities. A phase III randomized trial is planned for evaluating the benefit of neoadjuvant DOS chemotherapy in patients with locally advanced gastric cancer. [Table: see text]

Randomized phase III trial of standard D2 versus D2 + para-aortic lymph node (PAN) dissection (D) for clinically M0 advanced gastric cancer: JCOG9501

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. LBA4015-LBA4015 ◽  
Author(s):  
M. Sasako ◽  
T. Sano ◽  
S. Yamamoto ◽  
A. Nashimoto ◽  
A. Kurita ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Disease Free Survival ◽  
Operation Time ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Rank Test ◽  
R0 Resection ◽  
Eligibility Criteria ◽  
Curative Intent

LBA4015 Background: The INT-0116 study proved the efficacy of radiochemotherapy after R0 resection for gastric cancer and thus the importance of the local control and the insufficiency of D0/1 surgery. Recently D2 surgery was for the first time proven to improve the survival compared with D1 in a Taiwanese RCT (Lancet Oncol 2006). In our study, D2+PAND was compared with D2 in a RCT. Low operative mortality has been reported (Sano et al. J Clin Oncol 2004) and we now present the survival results. Methods: Eligibility criteria included; histologically proven adenocarcinoma, cT2b-T4, cM0, no macroscopic metastasis to the PAN, negative lavage cytology, adequate organ function, and age <76. Linitis plastica was excluded. Eligible pts were randomly assigned to D2 with or without PAND during surgery. All patients were followed without adjuvant therapy until recurrence. The primary endpoint was overall survival (OS) to be compared by stratified log-rank test. Assuming 256 eligible pts in each arm, the study had 75% power to detect 0.73 hazard ratio for D2+PAND to D2 in OS at 0.05 one-sided alpha. Results: Between 07/1995 and 04/2001, 523 pts were randomized (263 to D2 and 260 to D2+PAND). Baseline characteristics were well balanced between the arms. At the time of the final analysis on 23/03/06, 191 (96 and 95, in D2 and D2+PAND, respectively) had died. The 3- and 5-year OS were 76% and 69% in D2 and 76% and 70% in D2+PAND, respectively (p = 0.57, Hazard ratio was 1.03 (95% CI: 0.77–1.37)). Disease free survival did not show any difference between the groups as well. Median operation time was 63 minutes longer and median blood loss was 230 ml larger in D2+PAND than in D2. There was no difference in the incidence of major surgical complications and hospital mortality (0.8% in both arms). Conclusions: D2 or D2+PAND could be carried out safely and showed excellent survival for advanced gastric cancer treated with curative intent. PAND could not improve the survival achieved by D2. General use of PAND should be avoided. No significant financial relationships to disclose.

Oxaliplatin, irinotecan, and cetuximab in advanced gastric cancer. First efficacy results of a multicenter phase II trial (AGMT Gastric-2) of the Arbeitsgemeinschaft Medikamentoese Tumortherapie (AGMT)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4538-4538
Author(s):  
E. Woell ◽  
R. Greil ◽  
W. Eisterer ◽  
M. Fridrik ◽  
B. Grünberger ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Treatment Options ◽  
Objective Response ◽  
Sensory Neuropathy ◽  
Multicenter Phase ◽  
Grade 3 ◽  
Line Setting

4538 Background: Patients (pts.) suffering from advanced gastric cancer have still a poor prognosis and treatment options are limited. In our previous phase II trial (AGMT-Gastric-1) we could show that the combination of oxaliplatin and irinotecan was well tolerated and showed an objective response rate of 58% (Anticancer Res 28:2901–2906, 2008). This chemotherapy regimen was tested in combination with cetuximab in a multicenter phase II trial. Methods: Oxaliplatin 85 mg/m2 biweekly and irinotecan 125 mg/m2 biweekly were combined with cetuximab 400 mg/m2 loading dose and subsequently weekly 250 mg/m2. 51 patients with histological proven unresectable and/or metastatic gastric adenocarcinoma were treated in a first line setting. Median age: 62 years (range 19–79 years), PS 0: 25 patients, PS 1+2 26 patients, single metastatic site: 24 patients, multiple metastases: 27 patients. Results: Frequently reported adverse events (more than 20% of pts.) were predominantly grade 1 or 2 and included neutropenia (35% of pts.), thrombocytopenia (33%), anemia (73%), nausea (45%), diarrhea (57%), alopecia (22%), and fatigue (37%). Grade 3 and 4 toxicities included neutropenia in 9/1 pts., thrombocytopenia in 1/0 pts., anemia in 3/1 pts., nausea in 2/0 pts., and diarrhea in 7/2 pts. Sensory neuropathy occurred mostly as grade 1 and 2 in 37% of pts., in 7 pts. grade 3 neurotoxicity was observed. Acneiform skin rash grade 1 / 2 / 3 / 4 was reported in 31% / 20% / 6% / 2% of pts. respectively. 16 pts. went off-study due to neutropenia (n=5), nausea/vomiting (n=1), diarrhea (n=1), progressive disease (n=3), toxic colon (n=2), and allergic reaction to cetuximab at first (n=2), second (n=1) or third infusion (n=1). 35 patients are assessable for response with 1 pt. (3%) showing a CR, 21 pts. (60%) a PR, 7 pts. (20%) a SD and PD in 6 pts. (17%). A disease control rate was achieved in 83%. Median time to progression was 24.8 weeks (n=29), median overall survival 38.1 weeks (n=32). Conclusions: The combination of oxaliplatin and irinotecan with cetuximab is feasible, safe and active in advanced gastric cancer. [Table: see text]

Phase II trial of S-1 combined with oxaliplatin (SOX) as neoadjuvant chemotherapy for locally advanced gastric cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 122-122
Author(s):  
L. Chen
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
High Response Rate ◽  
R0 Resection ◽  
Locally Advanced Gastric Cancer

122 Background: Previous phase II trial with combination therapy of S-1 plus oxaliplatin (SOX) demonstrated high response rate and well tolerability in patients with untreated advanced gastric cancer. The aim of this phase II trial was to evaluate the efficacy and safety of SOX as neoadjuvant chemotherapy for locally advanced gastric cancer (AGC). Methods: Eligibility criteria included a histologically proven AGC with stage IIIb, IIIc (AJCC 7th edition), at least 1 measurable lesion, no prior chemotherapy, ECOG 0∼2, adequate hepatic, renal, and bone marrow function. Enrolled patients were staged by EUS and CT. The neoadjuvant chemotherapy consisted of 3-4 cycles of oxaliplatin (130 mg/m2) on day 1 and S-1 (80 mg/m2/day) for 14 days with 7 days rest. After chemotherapy, the patients underwent surgery. Results: From Dec 2009 to Sep 2010, 35 patients (IIIb; 19pts, IIIc; 16pts) were enrolled. The median age of the patients was 54.6 years (range; 20-72 y). All patients were available for evaluating the clinical responese and adverse events. The overall response rate was 68.5% (1CR, 23 PR, 9 SD, 2 PD). 32 patients underwent surgical resection. Of them, 27 patients underwent standard D2 surgery and 5 patients had palliative surgery. 25 patients had R0 resection. Postoperative pathological examination showed that most of the surgical patients were in T4a stage. According to Lauren classification, 71.9% patiens (23/32pts) were diffuse type, SOX showed higher respons rate (1CR, 20 PR, 2 SD, RR: 91.3%) among these patients. Major grade 3/4 hematological toxicities were anemia (5.7%), neutropenia (5.7%) and liver dysfunction (8.6%) and non-hematological toxicities were anorexia (5.7%) and vomiting (11.4%). But most of the adverse events were managable. Conclusions: Neoadjuvant chemotherapy with S-1 plus oxaliplatin (SOX) showed high response rate and and R0 resection rate for locally advanced GC, especially for diffuse type patients. All the patients did not have severe toxicity during the process of chemotherapy. This is the preliminary results, and the survival benefit in locally advanced GC patients that respond to SOX neoadjuvant chemotherapy needs to be addressed by a randomized-controlled trial. No significant financial relationships to disclose.

scholarly journals Laparoscopic or open distal gastrectomy after neoadjuvant chemotherapy for advanced gastric cancer: study protocol for a randomised phase II trial

BMJ Open ◽  
2018 ◽  
Vol 8 (8) ◽  
pp. e021633 ◽  
Author(s):  
Ziyu Li ◽  
Fei Shan ◽  
Xiangji Ying ◽  
Lianhai Zhang ◽  
Hui Ren ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Standard Treatment ◽  
Phase Ii Trial ◽  
Distal Gastrectomy ◽  
Sample Size Calculation ◽  
Cox Proportional Hazards Model ◽  
Open Distal Gastrectomy

IntroductionCurrent guidelines recommend open gastrectomy with D2 lymph node dissection and adjuvant chemotherapy as the standard treatment for advanced gastric cancer. However, the prognosis is not satisfactory. Perioperative chemotherapy has been proposed to improve survival. Although still in debate, the efficacy of laparoscopic distal gastrectomy (LDG) in patients with advanced gastric cancer has been demonstrated in a few trials. Therefore, LDG after neoadjuvant chemotherapy can be a candidate for future standard treatment on advanced distal gastric cancer. We propose a randomised phase II trial to compare LDG and open distal gastrectomy (ODG) after neoadjuvant chemotherapy for advanced gastric cancer.Methods and analysisTo test the efficacy and safety, a randomised, open-label, single-centre, phase II trial was designed to evaluate the non-inferiority of LDG compared with ODG after neoadjuvant chemotherapy, with 3-year recurrence-free survival as the primary endpoint. The chosen critical value of a non-inferiority margin was an increase of <8%. The study started in 2015 and enrolled 96 patients according to a prior sample size calculation. Intention-to-treat and per-protocol approach will be used for efficacy analysis, and as-treated analysis will be applied for safety analysis. The survival curves will be constructed as time-to-event plots using the Kaplan-Meier method and compared using log-rank tests and Cox proportional hazards model. All statistical analyses will be conducted in standard statistical software with a significance level of 0.05.Ethics and disseminationThis study was approved by the Peking University Cancer Hospital Ethics Committee. The results will be submitted for publication in peer-reviewed journals.Trial registration numberNCT02404753; Pre-results.

Updated results of a randomized phase II trial for neoadjuvant versus adjuvant docetaxel/cisplatin chemotherapy in patients with locally advanced gastric cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 111-111
Author(s):  
Young Woo Kim ◽  
Keun Won Ryu ◽  
Il Ju Choi ◽  
Myeong-Cherl Kook ◽  
Young Iee Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Phase Iii ◽  
Cancer Center ◽  
Locally Advanced Gastric Cancer ◽  
Randomized Phase Ii

111 Background: Recent phase III trials proved the role of adjuvant chemotherapy in patients with gastric cancer after D2 resection, but the optimal treatment sequence remains to be determined. Here we report long-term follow up results for the randomized phase II trial comparing between neoadjuvant and adjuvant docetaxel/cisplatin (DC) chemotherapy in patients with locally advanced gastric cancer (LAGC). Methods: Patients with LAGC (stage IIIA-IV) were stratified by Japanese staging system and randomized to either neoadjuvant or adjuvant weekly DC chemotherapy in the National Cancer Center of Korea from 2003 to 2005. FDG-PET/CT screening was employed to exclude patients with metastasis. Patients randomized to neoadjuvant arm received 3 cycles of DC regimen (docetaxel 36 mg/m2 and cisplatin 40 mg/m2 on days 1 and 8 every 3 weeks), followed by surgery (D2 dissection). In adjuvant arm, patients underwent surgery, followed by 3 cycles of the same DC chemotherapy regimen. Results: Neoadjuvant arm (n=43) demonstrated higher R0 resection rate than adjuvant arm (n=44) [81% v 73%], but the difference was not statistically significant. At a median follow-up for suriving patients of 7.2 years, there were no significant differences in OS and PFS between the two arms [Log rank P=0.93 and P=0.89, respectively]. Conclusions: The timing of perioperative DC chemotherapy does not affect the overall survival of patients with LAGC.

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