Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial

• Published in: The lancet oncology 2018-05, Vol.19 (5), p.616-628
• Main Authors: Cats, Annemieke, Jansen, Edwin P M, van Grieken, Nicole C T, Sikorska, Karolina, Lind, Pehr, Nordsmark, Marianne, Meershoek-Klein Kranenbarg, Elma, Boot, Henk, Trip, Anouk K, Swellengrebel, H A Maurits, van Laarhoven, Hanneke W M, Putter, Hein, van Sandick, Johanna W, van Berge Henegouwen, Mark I, Hartgrink, Henk H, van Tinteren, Harm, van de Velde, Cornelis J H, Verheij, Marcel, Van Coevorden, Frits, Vanhoutvin, Steven, Hulshof, Maarten CCM, Loosveld, Olaf JL, Ten Tije, A (Bert) Jan, Erdkamp, Frans LG, Warmerdam, Fabienne ARM, Van der Peet, Donald L, Verheul, Henk MW, Boerma, Djamila, Los, Maartje, Slot, Annerie, Houtsma, Danny, Portielje, Johanna EA, Blaisse, Reinoud JB, Spillenaar Bilgen, Ernst Jan, Polée, Marco B, Geenen, Maud M, Braak, Jeffrey PBM, Neelis, Karen J, Slingerland, Marije, Jansen, Rob LH, Buijsen, Jeroen, Beeker, Aart, Eijsbouts, Quirijn AJ, Van Riel, Johanna MGH, Rozema, Tom, Van Spronsen, Dick Johan, Meerum Terwogt, Jetske M, Tanis, Bea C, Van der Torren-Conze, Adelheid ME, Van Hilligersberg, Richard, Koopman, Miriam, Den Boer, Marien O, Creemers, Geert-Jan, Van der Sangen, Maurice, Rentinck, Marjolein EM, Van den Berg, H Pieter, Jonkers, Ge JPM, Grootenboers, Diane, Vulink, Annelie JE, Hovenga, Sjoerd, Van der Mijle, Huub CJ, Baars, Arnold, Haringhuizen, Annebeth W, Appels, Marije IE, Rietbroek, Ron C, Hendriksen, Ellen M, Legdeur, Marie-Cecile JC, Ten Bokkel Huinink, Daan, Van Dobbenburgh, O Aart, Smit, Jitty M, Van Bochove, Aart, Veldhuis, Gerrit-Jan, Muller, Erik W, Bonenkamp, J (Han) J, Braam, Pètra M, De Boer, Jaap, Van Halteren, Henk K, Valster, Fransje AA, Imholz, Alex LT, Van Dijk, Marjan A, Van der Gaast, Ate, Otten, J (Hans)-Martin MB, Ceha, Heleen M, Glimelius, Bengt, Lagerbäck, Cecillia, Perman, Mats, Johnsson, Anders, Borg, David, Nielsen, Niels H, Piwowar, Andrzej, Elmlund, Mattias, Hörberg, Helene, Edlund, Per, Johansson, Bengt, Flygare, Petra, Jespersen, Marie Louise
• Format: Article
• Language: English
• Subjects: Abdomen; Adenocarcinoma; Bone marrow; Cancer therapies; Chemoradiotherapy; Chemotherapy; Cisplatin; Colorectal carcinoma; Diarrhea; Epirubicin; Esophageal cancer; Esophagus; Gastric cancer; Intestine; Intravenous administration; Liver; Lymph nodes; Medical prognosis; Medicin och hälsovetenskap; Mortality; Neutropenia; Oxaliplatin; Patients; Radiation therapy; Skin cancer; Surgery; Surgical outcomes; Survival; Tablets; Tumors
• ISSN: 1470-2045; 1474-5488; 1474-5488
• DOI: 10.1016/S1470-2045(18)30132-3

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. 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/m2 on day 1), cisplatin (60 mg/m2 on day 1) or oxaliplatin (130 mg/m2 on day 1), and capecitabine (1000 mg/m2 orally as tablets twice daily for 14 days in combination with epirubicin and cisplatin, or 625 mg/m2 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/m2 orally twice daily on radiotherapy days) and cisplatin (20 mg/m2 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. Between Jan 11, 2007, and April 17