Controversies in the Treatment of Local and Locally Advanced Gastric and Esophageal Cancers

2015 ◽  
Vol 33 (16) ◽  
pp. 1754-1759 ◽  
Author(s):  
Deirdre J. Cohen ◽  
Lawrence Leichman
Keyword(s):  
Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Phase Iii ◽  
Postoperative Treatment ◽  
Treatment Regimens ◽  
Locally Advanced Gastric Cancer ◽  
Gastric Adenocarcinomas ◽  
Operative Specimen ◽  
Phase Iii Trials

Despite overall progress in the therapy of local and locally advanced esophageal, gastroesophageal junction, and gastric adenocarcinomas, death as a result of these tumors remains a common outcome. Most randomized phase III trials on which level-one evidence has been built have included the heterogeneous histologies and locations associated with these tumors. However, the different etiologies, molecular biology, and recurrence patterns associated with gastroesophageal malignancies suggest the need to split rather than lump. Biologic and response differences exist between squamous and adenocarcinomas, as well as diffuse and intestinal histologies. This may be a cause behind conflicting outcomes in similar trials. The accepted standard of chemoradiotherapy for locally advanced esophageal and gastroesophageal junction cancers is based on a few positive trials, with the best chemotherapy and total dose of radiation remaining controversial. In the West, the staging evaluations of locally advanced gastric cancer are not uniform. Yet, these evaluations will inform the results of preoperative and perioperative treatments. Although postoperative chemoradiotherapy for gastric cancer has been an accepted treatment option for the last decade, more recent studies have called into question the need for radiotherapy. In perioperative strategies, it has yet to be determined whether histologic or molecular changes in the operative specimen should inform postoperative treatment. An appropriate place for targeted therapy needs to be found in preoperative and postoperative treatment regimens. Finally, because so much is lost when trials are forced to close for lack of accrual, it is imperative to build multidisciplinary consensus before they are launched.

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]

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.

Phase II Trial of 4′-Epi-Doxorubicin in Locally Advanced or Metastatic Gastric Cancer

1988 ◽  
Vol 74 (3) ◽  
pp. 313-315 ◽  
Author(s):  
Eduardo Cazap ◽  
Roberto Estevez ◽  
Mario Bruno ◽  
Daniel Levy ◽  
Carlos Algamiz ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Adenocarcinoma ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Phase Iii ◽  
Future Studies ◽  
Phase Iii Trials

Patients with locally advanced or metastatic gastric adenocarcinoma received an i.v. bolus of 4′-epi-doxorubicin, 75/mg/m2/cycle, every 21 days. Partial responses were observed in 5 of 23 evaluable patients (21.7%). Treatment was generally well tolerated and toxicity was mild. The response rate to epirubicin appears to be very similar to that reported for doxorubicin. Larger doses of epirubicin could be safely used in future studies, and further evaluation of epirubicin in phase III trials is indicated.

Phase III study of first-line zolbetuximab + CAPOX versus placebo + CAPOX in Claudin 18.2+/HER2−advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: GLOW.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4648-TPS4648
Author(s):  
Manish A. Shah ◽  
Jaffer A. Ajani ◽  
Salah-Eddin Al-Batran ◽  
Yung-Jue Bang ◽  
Daniel Catenacci ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Phase Iii ◽  
Controlled Study ◽  
Her2 Status ◽  
First Line ◽  
Double Blind ◽  
Junction Protein

TPS4648 Background: Gastric cancer is the fourth leading cause of cancer death worldwide. Capecitabine + oxaliplatin (CAPOX) is a standard first-line treatment for advanced gastric cancer. Claudin (CLDN)18.2 has emerged as a promising targetable biomarker. In healthy tissue, CLDN18.2, a tight junction protein, is confined to gastric mucosa (ie, cells in the pit and base regions of gastric glands). Upon malignant transformation, structural loss in gastric or gastroesophageal junction (G/GEJ) adenocarcinoma cells may allow antibodies more access to previously unavailable CLDN18.2. Zolbetuximab is a chimeric IgG1 monoclonal antibody that specifically binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Results of a phase 2 study (NCT01630083) showed prolonged survival of patients with CLDN18.2-positive (CLDN18.2+) advanced G/GEJ adenocarcinoma treated with zolbetuximab + epirubicin, oxaliplatin, and capecitabine (EOX) vs EOX alone. Methods: This phase 3, double-blind, placebo-controlled study (NCT03653507) will enroll ~500 adult patients from global sites. Patients are required to have CLDN18.2+/HER2− locally advanced unresectable or metastatic G or GEJ adenocarcinoma that is radiographically evaluable per RECIST v1.1. Patients are not permitted to have received prior treatment with chemotherapy for advanced or metastatic G or GEJ adenocarcinoma. Patients will be randomly assigned 1:1 to receive either zolbetuximab plus CAPOX or placebo plus CAPOX. Randomization will be stratified by region (Asia vs non-Asia), number of metastatic sites (0 to 2 vs ≥3), and prior gastrectomy (yes vs no). Zolbetuximab will be administered at a loading dose of 800 mg/m2 IV on Cycle 1 Day 1 followed by 600 mg/m2 IV every 3 weeks. Central testing of tumor tissue will determine CLDN18.2 and HER2 status (if unknown); patients will be considered CLDN18.2+ if ≥75% of tumor cells demonstrate moderate-to-strong membranous immunohistochemical staining. The primary objective is to compare progression-free survival between treatment arms. Secondary endpoints are overall survival; objective response rate; duration of response; and the safety/tolerability, pharmacokinetics, and immunogenicity of zolbetuximab. As of January 31, 2020, 127 sites were active and open to enrollment. Clinical trial information: NCT03653507 .

scholarly journals Perioperative chemotherapy for gastric cancer: the current state

2018 ◽  
Vol 20 (2) ◽  
pp. 56-60
Author(s):  
V K Lyadov ◽  
O A Pardabekova ◽  
M A Lyadova
Keyword(s):  
Gastric Cancer ◽  
Malignant Tumors ◽  
Locally Advanced ◽  
High Rate ◽  
Phase Iii ◽  
Perioperative Chemotherapy ◽  
Phase Iii Trial ◽  
Locally Advanced Gastric Cancer ◽  
Current State ◽  
Resectable Gastric Cancer

Gastric cancer has one of the leading positions in the world in the prevalence and mortality among malignant tumors. The results of surgical treatment of locally advanced gastric cancer remain generally poor due to the high rate of relapse after surgery. Currently, perioperative (pre- and postoperative) chemotherapy in combination with surgery is recommended for patients with stage ≥IB resectable gastric cancer. We analyzed the studies devoted to the problem of choosing the optimal regimen of perioperative chemotherapy in locally advanced and oligometastatic gastric cancer. The highest efficacy was observed in the taxan-containing regimen FLOT which allowed to increase the median overall survival up to 50 months in a randomized controlled phase III trial. The use of perioperative chemotherapy with anti-Her2 therapy, immunotherapy or any other biologic drug remains investigational.

Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S) trial: Comparison of a sequential treatment with irinotecan (CPT-11) plus 5-fluorouracil (5-FU)/folinic acid (LV) followed by docetaxel and cisplatin versus a 5-FU/LV regimen as postoperative treatment for radically resected gastric cancer.

2012 ◽  
Vol 30 (18_suppl) ◽  
pp. LBA4001-LBA4001 ◽  
Author(s):  
Emilio Bajetta ◽  
Irene Floriani ◽  
Maria Di Bartolomeo ◽  
Roberto Labianca ◽  
Lorenza Landi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Gastroesophageal Junction ◽  
Current Trend ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Postoperative Treatment ◽  
Rank Test ◽  
Target Number ◽  
Significant Prolongation

LBA4001 Background: Following radical resection of gastric or gastroesophageal junction (GEJ) adenocarcinoma, a meta-analysis and randomized studies demonstrated better survival in pts treated with fluoropyrimidine regimens compared to surgery alone. ITACA-S trial is a no-profit, multicenter, randomized, open-label, superiority phase III study aimed at evaluating whether a more intensive postoperative chemotherapy improves efficacy, when replace fluoropyrimidine. Methods: Pts radically resected for gastric or GEJ adenocarcinoma, with ≥D1-lymphadenectomy, node involvement (pN+) or pN0 with pT2b-3-4; within 3-8 weeks after surgery were eligible. Treatment consisted in CPT-11 180 mg/m2 on d1, LV 100 mg/m2 d1-2, 5-FU 400-600 mg/m2 d1-2, q14; for 4 cycles (FOLFIRI regimen) followed by docetaxel 75 mg/m2 d1, cisplatin 75 mg/m2 d1, q 21; for 3 cycles (arm A) vs. LV 100 mg/m2 d1-2, 5-FU 400-600 mg/m2 d1-2, q 14 for 9 cycles (arm B). The primary hypothesis on disease-free survival (DFS) requires 636 events (first recurrence or death) to detect an hazard ratio (HR) of 0.80, with 2-sided 5% significance level for the log-rank test and a power of 80%. Results: From February 2005 to August 2009, 1,106 pts were randomized and 1,100 were analyzed (562 arm A, 538 arm B; 6 major violations) by 123 Italian centers. By March 2012, with a median follow-up of 49 months (quartile range: 36-62) we observed 558 events for DFS (HR 0.98; 95%CI 0.83-1.16;p=0.83) accounting for 88% of the target number and 440 deaths (HR: 1.00; 95%CI 0.83-1.20;p=0.98). Toxicity was consistent with literature. Given the data observed, both under the original hypothesis and the current trend, the probability to reach a statistically significant results at the target events is <0.0001. Conclusions: Adjuvant chemotherapy in gastric cancer with more intensive regimen did not result in a significant prolongation of DFS and OS when compared to bolus/infusion FU/LV regimen.

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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