Masanori Terashima1, Yoshiaki Iwasaki2, Junki Mizusawa3, Hiroshi Katayama3, Kenichi Nakamura3, Hitoshi Katai4, Takaki Yoshikawa5, Yuichi Ito6, Masahide Kaji7, Yutaka Kimura8, Motohiro Hirao9, Makoto Yamada10, Akira Kurita11, Masakazu Takagi12, Narikazu Boku13, Takeshi Sano14, Mitsuru Sasako15. 1. Division of Gastric Surgery, Shizuoka Cancer Center, 1007 Monagakubo, Nagaizumi-cho, Sunto-gun, Nagaizumi, Shizuoka, 411-8777, Japan. m.terashima@scchr.jp. 2. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 3. JCOG Data Center/Operations Office, National Cancer Center Hospital, Tokyo, Japan. 4. Department of Gastric Surgery, National Cancer Center Hospital, Tokyo, Japan. 5. Department of Gastrointestinal Surgery, Kanagawa Cancer Center Hospital, Yokohama, Japan. 6. Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan. 7. Department of Surgery, Toyama Prefectural Central Hospital, Toyama, Japan. 8. Department of Surgery, Sakai City Hospital, Sakai, Japan. 9. Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan. 10. Department of Surgery, Gifu Municipal Hospital, Gifu, Japan. 11. Department of Surgery, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan. 12. Department of Surgery, Shizuoka General Hospital, Shizuoka, Japan. 13. Department of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan. 14. Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 15. Department of Surgery, Hyogo College of Medicine, Kobe, Japan.
Abstract
BACKGROUND: The prognosis of patients with linitis plastica (type 4) and large (≥ 8 cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here. METHODS: Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279. RESULTS: From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240 min, respectively; p = 0.024). There were no significant differences in Grade 2-4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively). CONCLUSIONS: NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.
BACKGROUND: The prognosis of patients with linitis plastica (type 4) and large (≥ 8 cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here. METHODS: Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279. RESULTS: From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240 min, respectively; p = 0.024). There were no significant differences in Grade 2-4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively). CONCLUSIONS: NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.
Entities:
Keywords:
Large type 3; Linitis plastica; Neoadjuvant chemotherapy
Authors: I Songun; H J Keizer; J Hermans; P Klementschitsch; J E de Vries; J A Wils; J van der Bijl; J H van Krieken; C J van de Velde Journal: Eur J Cancer Date: 1999-04 Impact factor: 9.162
Authors: Salah-Eddin Al-Batran; Ralf D Hofheinz; Claudia Pauligk; Hans-Georg Kopp; Georg Martin Haag; Kim Barbara Luley; Johannes Meiler; Nils Homann; Sylvie Lorenzen; Harald Schmalenberg; Stephan Probst; Michael Koenigsmann; Matthias Egger; Nicole Prasnikar; Karel Caca; Jörg Trojan; Uwe M Martens; Andreas Block; Wolfgang Fischbach; Rolf Mahlberg; Michael Clemens; Gerald Illerhaus; Katja Zirlik; Dirk M Behringer; Wolff Schmiegel; Michael Pohl; Michael Heike; Ulrich Ronellenfitsch; Martin Schuler; Wolf O Bechstein; Alfred Königsrainer; Timo Gaiser; Peter Schirmacher; Wael Hozaeel; Alexander Reichart; Thorsten O Goetze; Mark Sievert; Elke Jäger; Stefan Mönig; Andrea Tannapfel Journal: Lancet Oncol Date: 2016-10-22 Impact factor: 41.316
Authors: H H Hartgrink; C J H van de Velde; H Putter; I Songun; M E T Tesselaar; E Klein Kranenbarg; J E de Vries; J A Wils; J van der Bijl; J H J M van Krieken Journal: Eur J Surg Oncol Date: 2004-08 Impact factor: 4.424
Authors: T Yoshikawa; M Sasako; S Yamamoto; T Sano; H Imamura; K Fujitani; H Oshita; S Ito; Y Kawashima; N Fukushima Journal: Br J Surg Date: 2009-09 Impact factor: 6.939
Authors: Salah-Eddin Al-Batran; Nils Homann; Claudia Pauligk; Gerald Illerhaus; Uwe M Martens; Jan Stoehlmacher; Harald Schmalenberg; Kim B Luley; Nicole Prasnikar; Matthias Egger; Stephan Probst; Helmut Messmann; Markus Moehler; Wolfgang Fischbach; Jörg T Hartmann; Frank Mayer; Heinz-Gert Höffkes; Michael Koenigsmann; Dirk Arnold; Thomas W Kraus; Kersten Grimm; Stefan Berkhoff; Stefan Post; Elke Jäger; Wolf Bechstein; Ulrich Ronellenfitsch; Stefan Mönig; Ralf D Hofheinz Journal: JAMA Oncol Date: 2017-09-01 Impact factor: 31.777
Authors: Nikolaos Charalampakis; Panagiota Economopoulou; Ioannis Kotsantis; Maria Tolia; Dimitrios Schizas; Theodore Liakakos; Elena Elimova; Jaffer A Ajani; Amanda Psyrri Journal: Cancer Med Date: 2017-12-13 Impact factor: 4.452