Journal ArticleDOI
Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial
Annemieke Cats,Edwin P.M. Jansen,Nicole C.T. van Grieken,Karolina Sikorska,Pehr Lind,Marianne Nordsmark,Elma Meershoek-Klein Kranenbarg,Henk Boot,Anouk K. Trip,HA A. Maurits Swellengrebel,Hanneke W. M. van Laarhoven,Hein Putter,Johanna W. van Sandick,Mark I. van Berge Henegouwen,Henk H. Hartgrink,Harm van Tinteren,Cornelis J.H. van de Velde,Marcel Verheij,Frits van Coevorden,Steven Vanhoutvin,Maarten C.C.M. Hulshof,Olaf Jl Loosveld,A (Bert) Jan Ten Tije,Frans L. G. Erdkamp,Fabiënne A. R. M. Warmerdam,Donald L. van der Peet,Henk M.W. Verheul,Djamila Boerma,Maartje Los,Annerie Slot,Danny Houtsma,Johanna E.A. Portielje,Reinoud J. B. Blaisse,Ernst Jan Spillenaar Bilgen,Marco B Polée,Maud M. Geenen,Jeffrey P.B.M. Braak,Karen J. Neelis,Marije Slingerland,Rob L. H. Jansen,Jeroen Buijsen,Aart Beeker,Quirijn A. J. Eijsbouts,Johanna Mgh Van Riel,Tom Rozema,Dick Johan van Spronsen,Jetske M. Meerum Terwogt,Bea C Tanis,Adelheid Me Van der Torren-Conze,Richard Van Hilligersberg,Miriam Koopman,Marien O Den Boer,Geert-Jan Creemers,Maurice J.C. van der Sangen,Marjolein Em Rentinck,H Pieter van den Berg,Ge Jpm Jonkers,Diane Grootenboers,Annelie Je Vulink,Sjoerd Hovenga,Huub van der Mijle,Arnold Baars,A. Haringhuizen,Marije Ie Appels,Ron C Rietbroek,Ellen M Hendriksen,Marie-Cecile Jc Legdeur,Daan Ten Bokkel Huinink,O Aart Van Dobbenburgh,Jitty M Smit,Aart Van Bochove,Gerrit-Jan Veldhuis,Erik W Muller,Johannes J. Bonenkamp,Pètra M Braam,Jaap De Boer,Henk K Van Halteren,Fransje Aa Valster,Alex L. T. Imholz,Marjan A Van Dijk,Ate van der Gaast,J (Hans)-Martin Mb Otten,Heleen M. Ceha,Bengt Glimelius,Cecillia Lagerbäck,Mats Perman,Anders Johnsson,David Borg,Niels H Nielsen,Andrzej Piwowar,Mattias Elmlund,Helene Hörberg,Per Edlund,Bengt Johansson,Petra Flygare,Marie Louise Jespersen +95 more
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TLDR
This investigator-initiated, open-label, randomised phase 3 trial aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma.Abstract:
Summary Background Both perioperative chemotherapy and postoperative chemoradiotherapy improve survival in patients with resectable gastric cancer from Europe and North America. To our knowledge, these treatment strategies have not been investigated in a head to head comparison. We aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma. Methods In this investigator-initiated, open-label, randomised phase 3 trial, we enrolled patients aged 18 years or older who had stage IB– IVA resectable gastric or gastro-oesophageal adenocarcinoma (as defined by the American Joint Committee on Cancer, sixth edition), with a WHO performance status of 0 or 1, and adequate cardiac, bone marrow, liver, and kidney function. Patients were enrolled from 56 hospitals in the Netherlands, Sweden, and Denmark, and were randomly assigned (1:1) with a computerised minimisation programme with a random element to either perioperative chemotherapy (chemotherapy group) or preoperative chemotherapy with postoperative chemoradiotherapy (chemoradiotherapy group). Randomisation was done before patients were given any preoperative chemotherapy treatment and was stratified by histological subtype, tumour localisation, and hospital. Patients and investigators were not masked to treatment allocation. Surgery consisted of a radical resection of the primary tumour and at least a D1+ lymph node dissection. Postoperative treatment started within 4–12 weeks after surgery. Chemotherapy consisted of three preoperative 21-day cycles and three postoperative cycles of intravenous epirubicin (50 mg/m 2 on day 1), cisplatin (60 mg/m 2 on day 1) or oxaliplatin (130 mg/m 2 on day 1), and capecitabine (1000 mg/m 2 orally as tablets twice daily for 14 days in combination with epirubicin and cisplatin, or 625 mg/m 2 orally as tablets twice daily for 21 days in combination with epirubicin and oxaliplatin), received once every three weeks. Chemoradiotherapy consisted of 45 Gy in 25 fractions of 1·8 Gy, for 5 weeks, five daily fractions per week, combined with capecitabine (575 mg/m 2 orally twice daily on radiotherapy days) and cisplatin (20 mg/m 2 intravenously on day 1 of each 5 weeks of radiation treatment). The primary endpoint was overall survival, analysed by intention-to-treat. The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02. Findings Between Jan 11, 2007, and April 17, 2015, 788 patients were enrolled and randomly assigned to chemotherapy (n=393) or chemoradiotherapy (n=395). After preoperative chemotherapy, 372 (95%) of 393 patients in the chemotherapy group and 369 (93%) of 395 patients in the chemoradiotherapy group proceeded to surgery, with a potentially curative resection done in 310 (79%) of 393 patients in the chemotherapy group and 326 (83%) of 395 in the chemoradiotherapy group. Postoperatively, 233 (59%) of 393 patients started chemotherapy and 245 (62%) of 395 started chemoradiotherapy. At a median follow-up of 61·4 months (IQR 43·3–82·8), median overall survival was 43 months (95% CI 31–57) in the chemotherapy group and 37 months (30–48) in the chemoradiotherapy group (hazard ratio from stratified analysis 1·01 (95% CI 0·84–1·22; p=0·90). After preoperative chemotherapy, in the total safety population of 781 patients (assessed together), there were 368 (47%) grade 3 adverse events; 130 (17%) grade 4 adverse events, and 13 (2%) deaths. Causes of death during preoperative treatment were diarrhoea (n=2), dihydropyrimidine deficiency (n=1), sudden death (n=1), cardiovascular events (n=8), and functional bowel obstruction (n=1). During postoperative treatment, grade 3 and 4 adverse events occurred in 113 (48%) and 22 (9%) of 233 patients in the chemotherapy group, respectively, and in 101 (41%) and ten (4%) of 245 patients in the chemoradiotherapy group, respectively. Non-febrile neutropenia occurred more frequently during postoperative chemotherapy (79 [34%] of 233) than during postoperative chemoradiotherapy (11 [4%] of 245). No deaths were observed during postoperative treatment. Interpretation Postoperative chemoradiotherapy did not improve overall survival compared with postoperative chemotherapy in patients with resectable gastric cancer treated with adequate preoperative chemotherapy and surgery. In view of the poor postoperative patient compliance in both treatment groups, future studies should focus on optimising preoperative treatment strategies. Funding Dutch Cancer Society, Dutch Colorectal Cancer Group, and Hoffmann-La Roche.read more
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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.
Salah-Eddin Al-Batran,Nils Homann,Claudia Pauligk,Thorsten Oliver Goetze,Johannes Meiler,Stefan Kasper,Hans-Georg Kopp,Frank Mayer,Georg Martin Haag,Kim Barbara Luley,U. Lindig,Wolff Schmiegel,Michael Pohl,Jan Stoehlmacher,Gunnar Folprecht,Stephan Probst,Nicole Prasnikar,Wolfgang Fischbach,Rolf Mahlberg,Jörg Trojan,Michael Koenigsmann,Uwe M. Martens,Peter C. Thuss-Patience,Matthias Egger,Andreas Block,Volker Heinemann,Gerald Illerhaus,Markus Moehler,Michael Schenk,Frank Kullmann,Dirk M Behringer,Michael Heike,Daniel Pink,Christian Teschendorf,Carmen Löhr,Helga Bernhard,G. Schuch,Volker Rethwisch,Ludwig Fischer von Weikersthal,Jörg T. Hartmann,Michael Kneba,Severin Daum,Karsten Schulmann,Jörg Weniger,Sebastian Belle,Timo Gaiser,Fuat Oduncu,Martina Güntner,Wael Hozaeel,Alexander Reichart,Elke Jäger,Thomas Kraus,Stefan Mönig,Wolf O. Bechstein,Martin Schuler,Harald Schmalenberg,Ralf Hofheinz,Flot Aio Investigators +57 more
TL;DR: In this article, the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin, and doceteaxel) as a perioperative therapy for patients with locally advanced, resectable tumours was reported.
Journal ArticleDOI
Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.
Elizabeth C Smyth,Marcel Verheij,William H. Allum,David Cunningham,Andrés Cervantes,Dirk Arnold +5 more
Journal ArticleDOI
The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer.
Feng Hua Wang,Lin Shen,Jin Li,Zhiwei Zhou,Han Liang,Xiao Tian Zhang,Lei Tang,Yan Xin,Jing Jin,Yu Jing Zhang,Xiang Lin Yuan,T. Liu,Guoxin Li,Qi Wu,Hui Mian Xu,Jiafu Ji,Yuan Fang Li,Xin Wang,Shan Yu,Hao Liu,Wen Long Guan,Rui-Hua Xu +21 more
TL;DR: This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis, comprehensive treatment, and follow-up visits for gastric cancer in China.
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)
TL;DR: In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared withperioperative ECF/ECX, and the number of toxic deaths was increased.
Journal ArticleDOI
Updates on Management of Gastric Cancer.
TL;DR: Treatment of gastric cancer is rapidly evolving in an effort to combat this challenging disease.
References
More filters
Journal ArticleDOI
Global cancer statistics, 2012
Lindsey A. Torre,Freddie Bray,Rebecca L. Siegel,Jacques Ferlay,Joannie Lortet-Tieulent,Ahmedin Jemal +5 more
TL;DR: A substantial portion of cancer cases and deaths could be prevented by broadly applying effective prevention measures, such as tobacco control, vaccination, and the use of early detection tests.
Journal ArticleDOI
Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer
David Cunningham,William H. Allum,Sally P. Stenning,Jeremy Thompson,Marianne Nicolson,J. Howard Scarffe,F. Lofts,Stephen Falk,Timothy Iveson,David Smith,Ruth E Langley,Monica Verma,Simon Weeden,Yu Jo Chua +13 more
TL;DR: In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival.
Journal ArticleDOI
Proportional hazards tests and diagnostics based on weighted residuals
TL;DR: In this article, Chen et al. showed that a treatment effect that decreases with time can be directly visualized by smoothing an appropriate residual plot, which can be expressed as a weighted least-squares line fitted to the residual plot.
Journal ArticleDOI
Chemoradiotherapy after Surgery Compared with Surgery Alone for Adenocarcinoma of the Stomach or Gastroesophageal Junction
John S. Macdonald,Stephen R. Smalley,Jacqueline Benedetti,Scott A. Hundahl,Norman C. Estes,Grant N. Stemmermann,Daniel G. Haller,Jaffer A. Ajani,Leonard L. Gunderson,J. Milburn Jessup,James A. Martenson +10 more
TL;DR: This investigation investigated the effect of surgery plus postoperative (adjuvant) chemoradiotherapy on the survival of patients with resectable adenocarcinoma of the stomach or gastroesophageal junction.
Journal ArticleDOI
Sequential treatment assignment with balancing for prognostic factors in the controlled clinical trial.
TL;DR: A new general procedure for treatment assignment is described which concentrates on minimizing imbalance in the distributions of treatment numbers within the levels of each individual prognostic factor.