![]() ![]() It will be interesting to note that could these results be generalized globally including asian population. The authors concluded that FLOT can be considered as new standard of care in perioperative setting for locally advanced resectable GEJ and gastric adenocarcinomas as it showed significant OS improvement compared to conventional ECF/ECX. More grade III/IV toxicities of infection (18%), neutropenia (51%), diarrhea (10%) and leukopenia(27%) were seen in FLOT group as compared to ECF/ECX. The FLOT was beneficial in all the subgroups analyzed, such as proximal versus distal tumors ( including Siewert I tumors). Regarding surgical morbidity and mortality, similar outcomes were observed in both group (30 days post-op mortality = 2% in the FLOT group and 3% in the ECF/ECX group) and surgical complications (51% in the FLOT group and 50% in the ECF/ECX). Patients achieving margin negative surgery (R0) were more in FLOT group (85% vs 78%, p=0.0162). More patients with ypN0 stage were seen in FLOT Group ( 49% vs 41%, p=0.025). Median OS in FLOT group was about 50 months as compared to 35 months in In the standards arm. The estimated 5 year OS was 45% in FLOT group and 36% in ECF/ECX. There were 11 progression or early deaths in ECF/ECX as compared to 6 patients in FLOT group after 4 preoperative chemotherapy. ![]() The primary outcome was OS and disease free survival (DFS) with intention to treat (ITT) analysis. Surgery was done after 4 weeks of last chemotherapy dose. Patient with ECOG 0-2 were included and interestingly 24% population was more than 70 years of age. 716 patients underwent randomization in which 360 were assigned to the standard regimen MAGIC with ECF/ECX (3 weekly cycle of Epirubicin=50mg/m2 D1, Cisplatin= 60mg/m2 D1, 5-FU= 200mg/m2 continous IV infusion D1-D21 or Oral Capecitabine= 1250mg/m2 BID D1-D21 on investigator's choice) and 356 to FLOT ( biweekly cycle of Docetaxel= 50mg/m2 D1, Oxaliplatin= 85mg/m2 D1, Leucovorin 200mg/m2 D1 and 5-FU= 2600mg/m2 24 hour infusion D1). Recently, randomized phase II/III trial of FLOT4 for locally advanced resectable gastric (44%) or GEJ (siewert I-II-III, 56%) non-metastatic adenocarcinoma was published in Lancet Journal (5). Significant clinical responses were seen in patients with more acceptable safety profile than classical DCF. Eventually, the FLOT regimen was evaluated in phase II trial in metastatic or unresectable gastric cancer patients (4). The classical DCF (taxane + platinum + fluoropyrimidine) regimen was associated with high toxicity profile with tolerability issues, failing to perform betterment than doublets, frontline. The role of Docetaxel has been investigated in gastric cancer in different settings and exerted significant activity in clinical trials (3). Both MAGIC and FNCLCC/FFCD demonstrated a significant improvement in OS in pts treated with perioperative chemotherapy regardless of anatomical location of tumor (GEJ or gastric) making this strategy a new standard of care in Europe. Control group underwent surgery alone and there was significant improvement in OS seen in chemotherapy group (38% vs 24%) with HR for death of 0.69 (95% CI, 0.50-0.89, p= 0.02). It has similar design to MAGIC trial and patient received 2-3 cycles of Cisplatin and 5-Flourouracil before and after surgery. Another landmark phase III trial done was FNCLCC/FFCD (2). The experimental arm showed significant improvement in 5 year OS (36%) with hazard ratio (HR) for death of 0.75 (95% Confidence interval (CI) 0.60-0.93, p=0.0009) as compared to surgery alone (23%). Patients received 3 cycles of ECF/ECX in pre and post operative settings. MAGIC trial is the first landmark trial, which showed overall survival (OS) improvement with perioperative chemotherapy in resectable gastric (74%), GEJ junction (11-12%) and lower esophageal adenocarcinoma (14-15%) (1). In fact, various trials showed an improvement in overall survival (OS) by using a perioperative treatment if compared with surgery. Multimodal approach represents the standard of care for treatment of resectable oesophageal and gastric cancer patients today, especially in the case of GEJ and cardial tumors. ![]() Gastroesophageal junction (GEJ) and gastric adenocarcinoma prognosis remains poor despite of recent advancement in therapies. ![]()
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