Trimodality treatment in gastric and gastroesophageal junction cancers: Current approach and future perspectives

Table 1 Postoperative chemoradiation clinical trials

Study name/phase	Size/stage/primary tumor location/histology	Intervention	Primary endpoint
INT-0116/phase III[37]	556 patients, IB-IVM0/stomach/adenocarcinoma	Gastrectomy D0-2 (both arms) AND E: 5-FU/LV + 45Gy radiation OR C: No post-surgical treatment	mOS: 27 m control vs 36 m experimental, HR: 1.35 (95% CI: 1.09-1.66, P = 0.005)
McNamara et al[87]/phase II	60 patients/T3-4/N1/M1a/esophagus/22% GEJ 78%/adenocarcinoma	Induction epirubicin, oxaliplatin, 5-FU → gastrectomy → E: adjuvant concurrent cisplatin, 5-FU + 50 to 55 Gy radiation	Surgical resection: 90% underwent surgical resection
Adelstein et al[39]/phase II	50 patients/T3/N1/M1a/esophagus/ 28% GEJ 72% adenocarcinoma 86% SCC 14%	Gastrectomy → E: cisplatin, 5-FU + 50.4-59.4 Gy radiation	OS rate: 51% 4-yr OS rate
Xie et al[42]/phase III	144 patients/T3-4/N1-3/stomach/adenocarcinoma	Gastrectomy D2 (both arms) AND E: capecitabine, oxaliplatin, 45 Gy radiation OR C: capecitabine, oxaliplatin	DFS rate: 72.8% experimental vs 76.3% control 3-yr DFS rate (P = 0.868)
ARTIST/phase III[43]	458 patients, IB-IV/stomach/adenocarcinoma (39% intestinal, 57% diffuse)	Gastrectomy D2 (both arms) AND E: capecitabine, cisplatin + 45 Gy radiation OR C: capecitabine, cisplatin	DFS rate: 78% experimental vs 74% control 3-yr DFS rate P = 0.0862
CRITICS/phase III[44]	788 patients/IΒ-IVA/stomach/ 83% GEJ 17% adenocarcinoma (32% intestinal 30% diffuse)	Preoperative epirubicin, cisplatin or oxaliplatin, capecitabine → Gastrectomy D1 (both arms) AND E: epirubicin, cisplatin or oxaliplatin, capecitabine or 5-FU + 45 Gy radiation OR C: epirubicin, cisplatin or oxaliplatin, capecitabine or 5-FU	mOS: 43 m control vs 37m experimental HR 1.01 (95%CI: 0.84-1.22; P = 0.90)
ARTIST 2/phase III[46]	538 patients/II/III N+/stomach/adenocarcinoma	Gastrectomy D2 (both arms) AND E1: S-1, oxaliplatin, + 45 Gy radiation OR E2: S-1, oxaliplatin ΟR C: S-1	DFS rate: 65% control, 78% experimental 2, 73% experimental 1 3-yr DFS rate experimental 2 vs experimental 1 HR 0.910, (P = 0.667)

mOS: Median overall survival; mDFS: Median disease-free survival; mPFS: Median progression-free survival; E: Experimental; C: Control; HR: Hazard ratio; 5-FU: 5-fluorouracil; LV: Leucovorin; Gy: Gray; S-1: Tegafur/gimeracil/oteracil; pCR: Pathologic complete response; GEJ: Gastroesophageal junction; CRT: Chemoradiation; AEG: Adenocarcinomas of the esophagogastric junction.