Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial

Al‐Batran, Salah‐Eddin; Homann, Nils; Pauligk, Claudia; Goetze, Thorsten Oliver; Meiler, Johannes; Kasper, Stefan; Kopp, Hans‐Georg; Mayer, Frank; Haag, Georg Martin; Luley, Kim; Lindig, Udo; Schmiegel, Wolff; Pohl, Michael; Stoehlmacher, Jan; Folprecht, Gunnar; Probst, Stephan; Prasnikar, Nicole; Fischbach, Wolfgang; Mahlberg, Rolf; Trojan, Jörg; Koenigsmann, Michael; Martens, Uwe M.; Thuss‐Patience, Peter; Egger, Matthias; Block, Andreas; Heinemann, Volker; Illerhaus, Gerald; Moehler, Markus; Schenk, Michael; Kullmann, Frank; Behringer, Dirk; Heike, Michael; Pink, Daniel; Teschendorf, Christian; Löhr, Carmen; Bernhard, Helga; Schuch, Gunter; Rethwisch, Volker; Weikersthal, Ludwig Fischer von; Hartmann, Jörg T.; Kneba, Michael; Daum, S; Schulmann, Karsten; Weniger, J.; Belle, Sebastian; Gaiser, Timo; Oduncu, Fuat; Güntner, Martina; Hozaeel, Wael; Reichart, Alexander; Jäger, Elke; Kraus, Thomas; Mönig, Stefan P.; Bechstein, Wolf O.; Schüler, Martin; Schmalenberg, Harald; Hofheinz, Ralf; Investigators, Flot Aio

doi:10.1016/s0140-6736(18)32557-1

Cited by 1,844 publications

(1,693 citation statements)

References 22 publications

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“…Presumably, the most commonly used multiagent chemotherapy combinations are epirubicin, cisplatin, and 5‐FU or capecitabine (ECF or ECX) and carboplatin and paclitaxel. It is interesting to note that 5‐FU and leucovorin, oxaliplatin, and docetaxel (FLOT)–based treatment has demonstrated significant improvements in survival compared with ECF/ECX, as reported in the FLOT4‐AIO study . However, to the best of our knowledge, the question of how this affects preoperative RT is unclear.…”

Section: Discussionmentioning

confidence: 96%

“…Randomized studies historically have been imprecise, spanning tumor subsites from the lower esophagus to the stomach, or had broad eligibility for the GEJ by including patients with Siewert I to III disease . Distinctions based on GEJ anatomy appear less and less pronounced in recent and ongoing trials . The NCDB typically does not contain any information regarding interventions and disease status after the initial course of treatment .…”

Section: Discussionmentioning

confidence: 99%

“…It is interesting to note that 5-FU and leucovorin, oxaliplatin, and docetaxel (FLOT)-based treatment has demonstrated significant improvements in survival compared with ECF/ECX, as reported in the FLOT4-AIO study. 27 However, to the best of our knowledge, the question of how this affects preoperative RT is unclear. Improvements in systemic treatment can highlight the importance of local therapies but also can make the separation of curves observed in the current study more pronounced.…”

Section: Discussionmentioning

confidence: 99%

“…2,17,28 Distinctions based on GEJ anatomy appear less and less pronounced in recent and ongoing trials. 7,27 The NCDB typically does not contain any information regarding interventions and disease status after the initial course of treatment. 29 Cause of death, disease progression, patterns of failure, and second-line treatments offered are unknown.…”

Section: Discussionmentioning

confidence: 99%

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Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy

Tian

Jiang

Madden

et al. 2019

Cancer

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Background Perioperative chemotherapy (POC) is one standard approach for the treatment of resectable cancers of the stomach and gastroesophageal junction (GEJ), whereas there has been growing interest in preoperative therapies. The objective of the current study was to compare survival between patients treated with preoperative chemoradiotherapy and adjuvant chemotherapy (PCRT) with those receiving POC using a large database. Methods The National Cancer Data Base was queried for patients diagnosed between 2004 and 2013 with American Joint Committee on Cancer clinical group stage IB to stage IIIC (excluding T2N0 disease) adenocarcinoma of the stomach or GEJ. Patients treated with definitive surgery and POC with or without preoperative radiotherapy of 41 to 54 Gy were included. Overall survival (OS) was defined from the date of definitive surgery and estimated using the Kaplan‐Meier method. A total of 14 patient and treatment variables were used for propensity score matching (PSM). Results A total of 1048 patients were analyzed: 53.2% received POC and 46.8% received PCRT. The primary tumor site was the GEJ in 69.1% of patients and stomach in 30.9% of patients. The median age of the patients was 60 years, and the median follow‐up was 25.8 months. The use of PCRT was associated with a greater pathologic complete response rate of 13.1% versus 8.2% (P = .01). POC was associated with a decreased risk of death in unmatched groups (hazard ratio [HR], 0.83; P = .043). Using PSM cohorts, POC decreased the risk of death with a median OS of 45.1 months versus 31.4 months (HR, 0.70; P = .016). The 2‐year OS rate was 72.9% versus 62.5% and the 5‐year OS rate was 40.7% versus 33.1% for POC versus PCRT, respectively. Survival favored POC in PSM gastric (HR, 0.41; P = .07) and GEJ (HR, 0.77; P = .08) patient subgroups. Conclusions The addition of preoperative radiotherapy to POC appears to be associated with an increased risk of death in patients with resectable gastric and GEJ cancers.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy

Tian

Jiang

Madden

et al. 2019

Cancer

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“…Additionally, Schuhmacher et al 11 failed to demonstrate the benefit of NACT vs D2‐gastrectomy alone. Recently, Al‐Batran et al 12 demonstrated the superiority of the FLOT4 schema when compared to ECF/ECX (Magic trial). However, patients with EGJ tumors were also included and 30% of the patients underwent esophagectomy.…”

Section: Introductionmentioning

confidence: 99%

Impact of neoadjuvant chemotherapy on surgical and pathological results of gastric cancer patients: A case‐control study

Charruf

Ramos

Pereira

et al. 2020

Journal of Surgical Oncology

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Background and Objective Neoadjuvant chemotherapy (NACT) followed by radical surgery represents a treatment option for patients with advanced gastric cancer (GC). This case‐control study aimed to evaluate the clinicopathological characteristics and surgical outcomes of GC patients who received NACT, and its impact on survival. Methods We retrospectively reviewed all patients with GC who underwent gastrectomy. A total of 45 cases with NACT were matched with consecutive 45 patients who underwent upfront gastrectomy for the following characteristics: gender, age, gastrectomy type, lymphadenectomy extent, American Society of Anesthesiologists class, histological type, cT and cN. Results NACT group had smaller tumors (4.9 vs 6.8 cm P = .006), lower lymphatic invasion rate (40% vs 73.3%, P = .001), lower venous invasion rate (18% vs 46.7%, P = .003) and lower perineural invasion rate (35% vs 77.8%, P < .0001). The ypTNM stage was lower in patients treated with NACT (P < .001). The major postoperative complication (POC) rate was lower in NACT patients (6.7% vs 24.4%, P = .02), as was hospital length of stay (10.8 vs 17 days, P = .005). Conclusions NACT allowed nodal and tumor downstaging. In addition, patients who underwent NACT had fewer POC and shorter length of hospital stay.

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Bringing Personalized Medicine to Precision Medicine in Gastroesophageal Cancer

2020

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Perioperative chemotherapy remains critical in improving long-term disease-free and overall survival outcomes among patients with locally advanced yet surgically resectable gastroesophageal adenocarcinoma (GEA). Fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) is a recognized standard treatment from the phase 3 FLOT4 trial, 1 but toxic effects limit its application to select patients such that doublet chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is also recommended in national guidelines. 2 Catenacci et al 3 present a single-group phase 2 trial exploring an alternative triplet chemotherapy regimen of fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX), in which all 3 cytotoxic agents have demonstrable activity in the metastatic setting. Thus, the report by Catenacci et al 3 presents a unique first application of this combination among patients with GEA that can be surgically resected with curative intent. Furthermore, the authors pursued a personalized pharmacogenomic approach in dosing the irinotecan (gFOLFIRINOX) based on the UGT1A1 genotype (OMIM 191740), using standardized assays for detection of germline

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Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial

Cited by 1,844 publications

References 22 publications

Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy

Survival outcomes in patients with gastric and gastroesophageal junction adenocarcinomas treated with perioperative chemotherapy with or without preoperative radiotherapy

Impact of neoadjuvant chemotherapy on surgical and pathological results of gastric cancer patients: A case‐control study

Bringing Personalized Medicine to Precision Medicine in Gastroesophageal Cancer

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