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.

Randomized phase II study to compare docetaxel plus S-1 with cisplatin plus S-1 in advanced gastric cancer without measurable lesions (HERBIS-3).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 119-119 ◽  
Author(s):  
Jin Matsuyama ◽  
Yukinori Kurokawa ◽  
Kazuhiro Nishikawa ◽  
Yutaka Kimura ◽  
Atsushi Takeno ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Advanced Gastric Cancer ◽  
Peritoneal Metastasis ◽  
Oral Intake ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Her2 Positive ◽  
Eligibility Criteria ◽  
Phase Iii Study

119 Background: Cisplatin and S-1 (CS) regimen is one of the standard chemotherapy as first-line for advanced gastric cancer. Docetaxel is a well-known agent with high anti-tumor effect for peritoneal metastasis from gastric cancer. A previous phase III study showed docetaxel plus S-1 (DS) regimen was recommended especially for advanced gastric cancer without measurable lesions. However, there was no study comparing the efficacy and safety of these two regimens. Methods: Eligibility criteria included HER2-negative unresectable or recurrent gastric adenocarcinoma, no measurable lesion according to RECIST v1.1, no massive peritoneal metastasis, no prior chemotherapy or radiotherapy, age ≤75, PS 0-2, adequate oral intake, and preserved organ functions. Patients were randomized to receive CS (cisplatin 60 mg/m² on day 8, S-1 40–60 mg twice a day for 3 weeks, every 5 weeks) or DS (docetaxel 40 mg/m² on day 1, S-1 40–60 mg twice a day for 2 weeks, every 3 weeks). Primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse events. Results: Sixty-one patients were randomly allocated the CS group (n = 31) or the DS group (n = 30) between Aug 2011 and Sep 2015. All were unresectable primary cases, and baseline characteristics were well balanced between the two groups. One patient was ineligible due to HER2-positive. There was no treatment-related death. The main grade 3 or worse adverse events were neutropenia (27% in CS vs. 40% in DS), anemia (10% in CS vs. 10% in DS), fatigue (13% in CS vs. 7% in DS), anorexia (10% in CS vs. 3% in DS), and diarrhea (10% in CS vs. 3% in DS). The median OS time were 15.8 months in CS and 20.0 months in DS, respectively (log-rank P = 0.113). Hazard ratio for OS was 0.617 (95%CI, 0.337 – 1.128). The median PFS time were 9.6 months in CS and 11.2 months in DS, respectively (log-rank P = 0.196). Hazard ratio for PFS was 0.698 (95%CI, 0.404 – 1.208). Conclusions: DS showed less toxic and more active profiles than CS for treatment of advanced gastric cancer without measurable lesions. The clinical benefit of DS regimen should be demonstrated in a phase III study. Clinical trial information: UMIN000006179.

Randomized phase III study of S-1 alone versus S-1 + cisplatin in the treatment for advanced gastric cancer (The SPIRITS trial) SPIRITS: S-1 plus cisplatin vs S-1 in RCT in the treatment for stomach cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4514-4514 ◽  
Author(s):  
H. Narahara ◽  
W. Koizumi ◽  
T. Hara ◽  
A. Takagane ◽  
T. Akiya ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Primary Endpoint ◽  
Standard Treatment ◽  
High Response Rate ◽  
Phase Iii ◽  
Rank Test ◽  
Open Label ◽  
Eligibility Criteria ◽  
Phase Iii Study

4514 Background: S-1 has been widely used against advanced gastric cancer (AGC) not only as monotherapy but also in combination with other cytotoxic compounds. Results of a phase I/II study combining S-1 + cisplatin (CDDP) were very encouraging with a high response rate (RR) of 76%, and the MST (Median Survival Time) of 383 days (Koizumi W et al, Br J Cancer, 2003). Based on these results, a phase III study comparing S-1 alone with S-1 + CDDP has been conducted to further evaluate the efficacy and safety for S-1 + CDDP as a standard treatment for AGC. Methods: This is a randomized, controlled, open-label, parallel, multicenter study. Patients (pts) are randomized to one of two treatment arms. Arm A: Pts receive oral S-1 (40 mg/m2) twice daily 28 days followed by 14 days rest. Arm B: Pts receive oral S-1 (40 mg/m2) twice daily 21 days followed by 14 days rest plus CDDP (60 mg/m2) iv on day 8. Eligibility criteria included unresectable/recurrent AGC, age 20–74, no prior chemotherapy for AGC. Primary endpoint was overall survival (OS). Main secondary endpoints included RR, time to treatment failure (TTF) and toxicity. Based on planned sample size of 284 pts, the trial was designed to have 90% power to detect an improvement in median OS from 8 to 12 months (2-sided log-rank test; significance level 0.05). Results: 305 pts (Arm A/B, 152/153) were randomized between Mar 2002 and Nov 2004. The eligible pts were 299 (Arm A/B, 150/149). Median age was 62.0/61.5 yrs. At a 2 yrs follow-up since last patient in, the MST for Arm A was 335.5 days (95%CI: 292.0 - 402.0) and for Arm B was 396.0 days (95%CI: 342.0 - 471.0). The OS for Arm B was superior to Arm A (log-rank p=0.0366, hazard ratio: 0.774, 95% CI: 0.608 - 0.985). RR was 31.1% for Arm A and 54.0% for Arm B. In Arm A vs Arm B, the most common grade 3/4 toxicities were: leucopenia, 2.0% vs 11.5%; neutropenia, 10.7% vs 39.9%; anemia (decreased Hb), 4.0% vs 25.7%; nausea, 1.3% vs 11.5%; anorexia, 6.0% vs 30.4%. No treatment related death was observed. Conclusions: The combination treatment of S-1 and CDDP met primary endpoint of OS, and was found to be effective and well tolerated in pts with AGC. Accordingly, this regimen can be regarded as one of first-line standard treatment for AGC. No significant financial relationships to disclose.

Primary results of a phase III trial to evaluate bursectomy for patients with subserosal/serosal gastric cancer (JCOG1001).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 5-5 ◽  
Author(s):  
Masanori Terashima ◽  
Yuichiro Doki ◽  
Yukinori Kurokawa ◽  
Junki Mizusawa ◽  
Hitoshi Katai ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Operation Time ◽  
Final Analysis ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Hospital Death ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Grade 3

5 Background: The role of bursectomy dissecting the peritoneal lining covering the pancreas and the anterior plane of the transverse mesocolon for preventing peritoneal metastasis had long been controversial. We conducted a phase III trial evaluating the role of bursectomy in patients with subserosal (SS) / serosal (SE) gastric cancer. Patient accrual had been completed on Mar. 2015. Methods: Eligibility criteria included histologically proven adenocarcinoma of the stomach; cT3(SS) or cT4a(SE). Patients were intraoperatively randomized to non-bursectomy arm or bursectomy arm. Primary endpoint was overall survival. A total of 1,200 patients were required to detect a hazard ratio of 0.77 with a one-sided alpha of 5% and 80% power. Results: Between Jun 2010 and Mar 2015, 1,204 patients were accrued from 57 institutions (non-bursectomy 602, bursectomy 602). Patients’ background and operative procedures were well balanced between the arms. After completion of patient enrollment, the second interim analysis was performed on Sep 2016, with 54% (196/363) of the expected events observed. The 3y-survival were 86.0% (95%CI, 82.7 to 88.7) in non-bursectomy arm and 83.3% (95%CI, 79.6 to 86.3) in bursectomy arm. Hazard ratio for bursectomy was 1.075 (98.5%CI: 0.760 to 1.520) with predictive probability in favor of bursectomy at the final analysis of 12.7%. These results led to early study termination based on the recommendation of the Data and Safety Monitoring Committee. Operation time was longer (median 222 min vs 254 min) and blood loss was larger (230 ml vs 330 ml) in bursectomy arm; however, the incidence of patients received blood transfusion was not different between the arms (4.8% vs 4.5%). Although the incidence of pancreatic fistula was a bit higher in bursectomy arm (2.5% vs 4.8%), the incidence of Grade 3 or higher complications was not different between the arms (11.6% vs 13.3%). Five patients in non-bursectomy arm and one patient in bursectomy showed in-hospital death. Conclusions: Although bursectomy can be safely performed without increasing morbidity and mortality, bursectomy was not recommended as a standard treatment for cT3 or cT4 gastric cancer. Clinical trial information: UMIN000003688.

scholarly journals Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial

2019 ◽  
Vol 37 (15) ◽  
pp. 1296-1304 ◽  
Author(s):  
Kazuhiro Yoshida ◽  
Yasuhiro Kodera ◽  
Mitsugu Kochi ◽  
Wataru Ichikawa ◽  
Yoshihiro Kakeji ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Interim Analysis ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Stage Iii ◽  
Rank Test ◽  
R0 Resection ◽  
Relapse Free Survival ◽  
Free Survival

PURPOSE S-1 is a standard postoperative adjuvant chemotherapy for patients with stage II or III gastric cancer in Asia. Neoadjuvant or perioperative strategies dominate in Western countries, and docetaxel has recently shown significant survival benefits when combined with other standard regimens in advanced cancer and perioperative settings. PATIENTS AND METHODS This randomized phase III study was designed to prove the superiority of postoperative S-1 plus docetaxel over S-1 alone for R0 resection of pathologic stage III gastric cancer. The sample size of 1,100 patients was necessary to detect a 7% increase in 3-year relapse-free survival as the primary end point (hazard ratio, 0.78; 2-sided α = .05; β = .2). RESULTS The second interim analysis was conducted when the number of events reached 216 among 915 enrolled patients (median follow-up, 12.5 months). Analysis demonstrated the superiority of S-1 plus docetaxel (66%) to S-1 (50%) for 3-year relapse-free survival (hazard ratio, 0.632; 99.99% CI, 0.400 to 0.998; stratified log-rank test, P < .001), and enrollment was terminated as recommended by the independent data and safety monitoring committee. Incidences of grade 3 or greater adverse events, particularly neutropenia and leukopenia, were higher in the S-1 plus docetaxel group, but all events were manageable. CONCLUSION Addition of docetaxel to S-1 is effective with few safety concerns in patients with stage III gastric cancer. The present findings may also be applicable in countries in which perioperative adjuvant chemotherapy or chemoradiation is not standard.

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.

scholarly journals Three-year outcomes of the randomized phase III SEIPLUS trial of extensive intraoperative peritoneal lavage for locally advanced gastric cancer

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jing Guo ◽  
Aman Xu ◽  
Xiaowei Sun ◽  
Xuhui Zhao ◽  
Yabin Xia ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Peritoneal Lavage ◽  
Randomized Study ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Phase Iii ◽  
Free Survival ◽  
Locally Advanced Gastric Cancer

AbstractWhether extensive intraoperative peritoneal lavage (EIPL) after gastrectomy is beneficial to patients with locally advanced gastric cancer (AGC) is not clear. This phase 3, multicenter, parallel-group, prospective randomized study (NCT02745509) recruits patients between April 2016 and November 2017. Eligible patients who had been histologically proven AGC with T3/4NxM0 stage are randomly assigned (1:1) to either surgery alone or surgery plus EIPL. The results of the two groups are analyzed in the intent-to-treat population. A total of 662 patients with AGC (329 patients in the surgery alone group, and 333 in the surgery plus EIPL group) are included in the study. The primary endpoint is 3-year overall survival (OS). The secondary endpoints include 3-year disease free survival (DFS), 3-year peritoneal recurrence-free survival (reported in this manuscript) and 30-day postoperative complication and mortality (previously reported). The trial meets pre-specified endpoints. Estimated 3-year OS rates are 68.5% in the surgery alone group and 70.6% in the surgery plus EIPL group (log-rank p = 0.77). 3-year DFS rates are 61.2% in the surgery alone group and 66.0% in the surgery plus EIPL group (log-rank p = 0.24). The pattern of disease recurrence is similar in the two groups. In conclusion, EIPL does not improve the 3-year survival rate in AGC patients.

Disease-free and overall survival in nonmetastatic esophageal or gastroesophageal junctional cancer after treatment with curative intent: A nationwide population-based study.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 246-246
Author(s):  
Marieke Pape ◽  
Pauline A.J. Vissers ◽  
Laurens Beerepoot ◽  
Mark I. Van Berge Henegouwen ◽  
Sjoerd Lagarde ◽  
...  
Keyword(s):  
Overall Survival ◽  
Performance Status ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Rank Test ◽  
R0 Resection ◽  
Real World Data ◽  
Curative Intent ◽  
Netherlands Cancer Registry ◽  
Disease Free

246 Background: Among patients with potentially curable esophageal cancer (EC) or gastroesophageal junctional cancer (GEJC) treated with curative intent, survival remains poor and around half of these patients have disease recurrence within a few years. This study addresses the need for real-world data on disease-free survival (DFS) and overall survival (OS) in patients with EC or GEJC who underwent potentially curative treatment. Methods: Patients selected from the nationwide Netherlands cancer registry (NCR) had received a primary diagnosis of non-metastatic EC or GEJC (excluding patients with T4b tumors) in 2015 or 2016 and received treatment with curative intent. Curative intent was defined as receiving resection (with or without [neo]adjuvant therapy) or definitive chemoradiotherapy (dCRT) without surgery. DFS and OS were analysed using Kaplan-Meier curves with Log-Rank test from resection date or end of dCRT. A sub-analysis was performed for NCR patients selected to align with the population of the CheckMate-577 phase 3 study of adjuvant nivolumab, i.e. patients with non-cervical stage II/III disease, R0 resection and residual pathological disease after neoadjuvant CRT (nCRT) and surgery. Results: We identified 1916 patients of median age of 67 years and predominantly male (76%). The majority (79%) received surgery and 21% of patients received dCRT. In resected patients, 83% received nCRT, 10% neoadjuvant chemotherapy (with or without adjuvant CRT) and 7% received no (neo)adjuvant treatment. Compared to the resected group, the population receiving dCRT had significantly fewer males (65% vs 78%), a higher median age (72 vs 65 years) and worse performance status. Patients receiving dCRT significantly shorter median DFS (14.2 months) and OS (20.9 months) compared to resected patients (DFS: 26.4 months, p < 0.001; OS: 40.5 months, p < 0.001). The 1- and 3-year DFS probabilities were 68% and 44%, respectively, in resected patients, and 56% and 24%, respectively, in patients receiving dCRT. In patients receiving nCRT followed by surgery, the median DFS and OS were 25.2 and 38.0 months, respectively, and 1- and 3-year DFS probabilities were 67% and 43%, respectively. In the sub-analysis (n = 725) the median DFS and OS were 19.2 and 29.4 months, respectively, and the 1- and 3-year DFS rates were 62% and 36%, respectively. Conclusions: Although patients are treated with curative intent, a considerable amount of patients with non-metastatic EC or GEJC experienced recurrence within two years. Resected patients had a higher DFS and OS compared to patients receiving dCRT.

Phase III trial of adjuvant capecitabine/cisplatin (XP) versus capecitabine/cisplatin/RT (XPRT) in resected gastric cancer with D2 nodal dissection (ARTIST trial): Safety analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4537-4537 ◽  
Author(s):  
J. Lee ◽  
W. Kang ◽  
D. Lim ◽  
J. Park ◽  
Y. Park ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Chemoradiation Therapy ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Phase Iii Trial ◽  
Free Survival ◽  
Resected Gastric Cancer ◽  
Disease Free

4537 Background: Although the adjuvant chemoradiation therapy has gained popularity and has become the standard of care in patients with resected gastric cancer in U.S., the role of chemoradiation therapy after extended D2 dissection has been questioned. We conducted a phase III trial to compare capecitabine/cisplatin (XP) vs XP + radiotherapy (RT) in curatively D2 resected gastric cancer patients in terms of disease free survival and overall survival. Methods: Eligibility criteria were as follows: stage Ib (T1N1, T2bN0) - IV (M1 excluded), curatively ≥ D2 resected gastric adenocarcinoma. XP only: X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 repeated every 3 weeks, 6 cycles; XP + RT: X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 x 2 cycles ⋄ RT 45 Gy (25 fractions) + X 1,650 mg/m2/d during RT ⋄ X 2,000 mg/m2/d D1∼14, CDDP 60 mg/m2 D1 x 2 cycles. The primary endpoint is 3-year disease-free survival. Results: From October 2004 to April 2008, 458 patients (XP arm: 228 patients; XP/RT arm: 230 patients) were enrolled. In XP arm, 172 (75%) of 228 enrolled patients completed 6 cycles of chemotherapy. In XP + RT arm, 188 (82%) of 230 patients completed the full course of XP 2 cycles - X + RT - XP 2 cycles. Conclusions: Safety and feasibility analysis of the two arms will be reported at the meeting. 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]

GAIN-2: Neo-/adjuvant phase III trial to compare intense dose-dense chemotherapy (CT) to tailored dose-dense CT in patients (pts) with high risk early breast cancer (EBC): Results on safety and interim invasive disease-free survival (iDFS).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 516-516
Author(s):  
Volker Moebus ◽  
Hans-Joachim Lueck ◽  
Ekkehart Ladda ◽  
Peter Klare ◽  
Marcus Schmidt ◽  
...  
Keyword(s):  
High Risk ◽  
Cranial Nerves ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Phase Iii ◽  
Rank Test ◽  
Luminal A ◽  
Luminal B ◽  
Grade 3 ◽  
Dose Dense

516 Background: GAIN-2 (NCT01690702) compared efficacy and safety of intense, dose-dense epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) vs dose-dense, dose-tailored epirubicin/ cyclophosphamide followed by dose-dense, dose-tailored docetaxel (dtEC-dtD) as adjuvant or neoadjuvant CT for node-positive or high risk node-negative EBC. Here, we report safety results and interim analysis (IA) of the primary endpoint iDFS. Methods: Pts (luminal A ≥N2; luminal B N+; HER2+ and TNBC) were randomized between iddEnPC (E 150 mg/m2, nP 330 mg/m2, C 2000 mg/m2, all q2w x 3) or dtEC-dtD (dtEC q2w x 4 followed after 1 week rest by dtD q2w x 4). Primary objective was to compare iDFS. 797 events are needed to detect a hazard ratio of 0.819 with a 2-sided log-rank-test with 80% power and α=0.05. The IA of iDFS was planned after 50% of the events have occurred. Safety and compliance were secondary objectives. Results: Between 10/2012 and 09/2018, 2887 pts were randomized and 2857 started treatment (iddEnPC 1429; dtEC-dtD 1428). Median age was 51 (range 18-75) years. Overall, 18.1% were luminal A, 31.5% luminal B/HER2-, 18.8% hormone-receptor (HR)+/HER2+, 8.5% HR-/HER2+ and 23.2% TNBC. Overall, 88.1% of pts completed all treatment in both arms. 66.8% with iddEnPC vs 58.8% with dtEC-dtD delayed CT dose (p<0.001). Grade 3-4 non-hematological adverse events (AEs) were more frequent with iddEnPC (iddEnPC 50.8% vs dtEC-dtD 45.1%, p=0.002). Grade 3-4 leukopenia, neutropenia, febrile neutropenia, arthralgia, and peripheral sensory neuropathy were significantly higher with iddEnPC. There were 1464 serious AEs (iddEnPC 870 vs dtEC-dtD 594) and 26 (9 vs 17) predefined AEs of special interest (anaphylaxis, any AE affecting cranial nerves, macula edema). Two deaths occurred during dtEC-dtD. After a median follow-up of 45.8 months, there was no difference in iDFS between arms (log-rank p=0.9102, hazard ratio iddEnPC vs dtEC-dtD 1.01, 95% CI 0.83-1.23). Conclusions: No new safety concerns were observed. Use of both iddEnPC and dtEC-dtD appears feasible in the (neo)adjuvant treatment of high risk EBC. Clinical trial information: NCT01690702 .

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