Epirubicin, oxaliplatin, and capectabine is just as "MAGIC"al as epirubicin, cisplatin, and fluorouracil perioperative chemotherapy for resectable locally advanced gastro-oesophageal cancer

Sirohi, Bhawna; Barreto, Savio George; Singh, Ashish; Batra, Swati; Mittra, Abhishek; Rastogia, Sameer; Ramadwar, Mukta; Shetty, Nishitha; Goel, Mahesh; Shrikhande, Shailesh V.

doi:10.4103/0973-1482.146122

Cited by 18 publications

(9 citation statements)

References 20 publications

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“…42% patient completed CAPOX and 58% EOX regimen. The baseline patient profile, responses and toxicities of CAPOX and EOX are comparable to other studies [5,6,[14][15][16][17][18]. Both the chemotherapy regimens were well tolerated.…”

Section: Kayal S Austin Publishing Groupsupporting

confidence: 66%

First Line Treatment for Advanced Gastroesophageal Cancer: Capecitabine Plus Oxaliplatin (CAPOX) versus Epirubicin, Oxaliplatin Plus Capecitabine (EOX)

Kayal¹

2017

Austin J Cancer Clin Res

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Chemotherapy is the mainstay of treatment for advanced gastroesophageal cancer (AGC). There is no consensus whether doublet or triplet chemotherapy is better. Hence our study aimed to compare CAPOX (capecitabine and oxaliplatin) with EOX (epirubicin, oxaliplatin plus capecitabine) as first line treatment for AGC. From December 2012 to July 2014, total of 69 patients were randomly assigned; 35 to EOX arm (epirubicin 50 mg/m 2 on day1, capecitabine 625 mg/m 2 twice daily for 21 day and oxaliplatin 130 mg/m 2 on day1 three weekly for 8 cycle) and 34 to CAPOX arm (capecitabine 1000 mg/m 2 twice daily for 14 days and oxaliplatin 130 mg/m 2 on day 1 in a three weekly cycle for 8 cycle). Median age at diagnosis was 55 years. The median number of chemotherapy cycle delivered was 7.45% completed planned treatment. 63.8% patient needed dose modification and 33.3% had treatment discontinuation due to grade 3/4 toxicity. Incidence of grade 3/4 neutropenia was significantly more in EOX where as diarrhoea and vomiting were more in CAPOX group. The ORR (overall response rate) was 63% in the entire cohort and 54.5% and 71.4% in the CAPOX and EOX group respectively. Median follow up was 15.2 month. Median OS (overall survival) was 8.1 and 10.3 months in the CAPOX and EOX groups respectively; p=0.298, however there was a trend favouring PFS (progression free survival) in the EOX group (5.5 vs. 8.3 months in CAPOX and EOX respectively; p=0.06). No significant difference was observed between the two regimens with respect to ORR, PFS and OS. Doublet chemotherapy regimen (CAPOX) has similar efficacy as a triplet regimen (EOX), however, with higher incidence of gastrointestinal toxicity.

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Section: Kayal S Austin Publishing Groupsupporting

confidence: 66%

First Line Treatment for Advanced Gastroesophageal Cancer: Capecitabine Plus Oxaliplatin (CAPOX) versus Epirubicin, Oxaliplatin Plus Capecitabine (EOX)

Kayal¹

2017

Austin J Cancer Clin Res

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“…Cisplatin is used in the treatment of gastric adenocarcinomas [34, 35], and we tested whether gastrin induced autophagy could modify the cellular response to cisplatin in vitro. Initially, AGS-Gr cells were treated with increasing concentrations of cisplatin (1–90 μM) in the presence and absence of gastrin for 24 h, 48 h and 72 h. The numbers of surviving cells were determined by their metabolic activity (XTT assay).…”

Section: Blocking Of Autophagy Reduces Gastrin-induced Cell Survivalmentioning

confidence: 99%

Gastrin activates autophagy and increases migration and survival of gastric adenocarcinoma cells

et al. 2017

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BackgroundThe peptide hormone gastrin exerts a growth-promoting effect in both normal and malignant gastrointestinal tissue. Gastrin mediates its effect via the cholecystokinin 2 receptor (CCKBR/CCK2R). Although a substantial part of the gastric adenocarcinomas express gastrin and CCKBR, the role of gastrin in tumor development is not completely understood. Autophagy has been implicated in mechanisms governing cytoprotection, tumor growth, and contributes to chemoresistance. This study explores the role of autophagy in response to gastrin in gastric adenocarcinoma cell lines.MethodsImmunoblotting, survival assays and the xCELLigence system were used to study gastrin induced autophagy. Chemical inhibitors of autophagy were utilized to assess the role of this process in the regulation of cellular responses induced by gastrin. Further, knockdown studies using siRNA and immunoblotting were performed to explore the signaling pathways that activate autophagy in response to gastrin treatment.ResultsWe demonstrate that gastrin increases the expression of the autophagy markers MAP1LC3B-II and SQSTM1 in gastric adenocarcinoma cells. Gastrin induces autophagy via activation of the STK11-PRKAA2-ULK1 and that this signaling pathway is involved in increased migration and cell survival. Furthermore, gastrin mediated increase in survival of cells treated with cisplatin is partially dependent on induced autophagy.ConclusionThis study reveals a novel role of gastrin in the regulation of autophagy. It also opens up new avenues in the treatment of gastric cancer by targeting CCKBR mediated signaling and/or autophagy in combination with conventional cytostatic drugs.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3055-5) contains supplementary material, which is available to authorized users.

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“…The data also suggests that performance of D2 gastrectomy in high-volume centers is feasible, with manageable perioperative morbidity and mortality rates [1719]. Currently, D2 gastrectomy is the standard surgical treatment for gastric cancer at our institution.…”

Section: Discussionmentioning

confidence: 99%

“…The REAL 2 analysis showed that the ECF and EOX regimens were equally effective, albeit for advanced tumors, whereas a meta-analysis of the data from the REAL 2 and ML17032 trials suggested better response rates and overall survival (OS) rates with capecitabine combinations [13141516]. These encouraging data for EOX, coupled with the ease of EOX administration as performed at our center [17], support the use of EOX for treatment of LA gastric cancer in the perioperative setting, thereby maximize its benefits. The analysis presented herein describes the treatment patterns and outcomes of patients with LA gastric cancer who received EOX at the Tata Memorial Hospital (TMH), a tertiary cancer center.…”

Section: Introductionmentioning

confidence: 93%

Perioperative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy in Locally Advanced Gastric Cancer: Safety and Feasibility in an Interim Survival Analysis

Ostwal

Sahu²,

Ramaswamy

et al. 2017

J Gastric Cancer

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PurposePerioperative chemotherapy improves survival outcomes in locally advanced (LA) gastric cancer.Materials and MethodsWe retrospectively analyzed patients with LA gastric cancer who were offered perioperative chemotherapy consisting of epirubicin, oxaliplatin, and capecitabine (EOX) from May 2013 to December 2015 at Tata Memorial Hospital in Mumbai.ResultsAmong the 268 consecutive patients in our study, 260 patients (97.0%) completed neoadjuvant chemotherapy, 200 patients (74.6%) underwent D2 lymphadenectomy, and 178 patients (66.4%) completed adjuvant chemotherapy. The median follow-up period was 17 months. For the entire cohort, the median overall survival (OS), 3-year OS rate, median progression-free survival (PFS), and 3-year PFS rate were 37 months, 64.4%, 31 months, and 40%, respectively. PFS and OS were significantly inferior in patients who presented with features of obstruction than in those who did not (P=0.0001). There was no difference in survival with respect to tumor histology (well to moderately differentiated vs. poorly differentiated, signet ring vs. non-signet ring histology) or location (proximal vs. distal). Survival was prolonged in patients with an early pathological T stage and a pathological node-negative status. In a multivariate analysis, postoperative pathological nodal status and gastric outlet obstruction on presentation significantly correlated with survival.ConclusionsEOX chemotherapy with curative resection and D2 lymphadenectomy is a suggested alternative to the existing perioperative regimens. The acceptable postoperative complication rate and relatively high resection, chemotherapy completion, and survival rates obtained in this study require further evaluation and validation in a clinical trial.

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Epirubicin, oxaliplatin, and capectabine is just as "MAGIC"al as epirubicin, cisplatin, and fluorouracil perioperative chemotherapy for resectable locally advanced gastro-oesophageal cancer

Abstract: In patients with resectable GO adenocarcinoma, it is possible to deliver the MAGIC-type perioperative chemotherapy with EOX with better compliance, toxicity, and efficacy rates.

Cited by 18 publications

References 20 publications

First Line Treatment for Advanced Gastroesophageal Cancer: Capecitabine Plus Oxaliplatin (CAPOX) versus Epirubicin, Oxaliplatin Plus Capecitabine (EOX)

First Line Treatment for Advanced Gastroesophageal Cancer: Capecitabine Plus Oxaliplatin (CAPOX) versus Epirubicin, Oxaliplatin Plus Capecitabine (EOX)

Gastrin activates autophagy and increases migration and survival of gastric adenocarcinoma cells

Perioperative Epirubicin, Oxaliplatin, and Capecitabine Chemotherapy in Locally Advanced Gastric Cancer: Safety and Feasibility in an Interim Survival Analysis

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