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

Table 2 Preoperative chemoradiation clinical trials

Study name/phase	Size/stage/primary tumor location/histology	Intervention	Primary endpoint
Rivera et al[47]/phase II	23 patients/II-IV, M0/stomach/57% GEJ 43% adenocarcinoma	Irinotecan, cisplatin + 45 Gy radiation → surgery	pCR: 2/23 (9%) achieved pCR after CRT
RTOG 9904/phase II[48]	43 patients/IB-III/stomach/adenocarcinoma	Cisplatin, 5-FU/LV + 45 Gy radiation → gastrectomy	pCR: 26% achieved pCR
S0356/phase II[49]	93 patients/II-III/esophagus/60% GEJ 40% adenocarcinoma	Oxaliplatin, 5-FU + 45 Gy radiation → surgery	pCR: 28% achieved pCR
Ilson et al[50]/phase II	55 patients/uT1N1M0-uT2-4NanyM0/esophagus 67% GEJ 33%/adenocarcinoma 75% SCC 22%	Cisplatin, irinotecan + 50.4 Gy radiation → surgery	pCR: 16% achieved pCR
Ajani et al[51]/phase II	126 patients/II-III/esophagus 3.2% GEJ 96.8% (AEG1 64.3%, AEG2 32.5%)/adenocarcinoma 96.8% SCC 3.2%	E: induction oxaliplatin, 5-FU OR C: no induction chemotherapy AND oxaliplatin, 5-FU + 50.4 Gy radiation → surgery (both arms)	pCR: 13% control vs 26% experimental (P = 0.094)
NeoRes/phase II[54]	181 patients/T1-3, Nany (except T1N0)/esophagus 82% GEJ 18%/adenocarcinoma 72% SCC 28%	E: cisplatin, 5-FU + 40 Gy radiation OR C: cisplatin, 5-FUAND surgery (both arms)	pCR: 28% experimental vs 9% control
CALGB 9781/phase III[56]	56 patients/T1-3Nany/esophagus/ GEJ adenocarcinoma 75% SCC 25%	E: cisplatin, 5-FU + 50.4 Gy radiation OR C: no preoperative treatment AND surgery (both arms)	mOS: 4.48 y experimental vs 1.79 y control (P = 0.002)
POET/phase III[52]	119 patients/T3-4/GEJ/adenocarcinoma	E: induction cisplatin, 5-FU/LV → cisplatin, etoposide + 30 Gy radiation OR C: cisplatin, 5-FU/LV AND surgery	OS rate: 46.7% experimental vs 26.1% control 3-yr OS HR 0.65, (95%CI: 0.42-1.01, P = 0.055)
CROSS/phase III[57]	366 patients/T1N1, T2-3N0-1/esophagus 73.2% GEJ 24%/adenocarcinoma 75% SCC 23%	E: carboplatin, paclitaxel + 41.4 Gy radiation OR C: no chemoradiation AND surgery (both arms)	mOS: 49.4 m experimental vs 24 m control HR 0.657, (95%CI: 0.495-0.871, P = 0.003)
Neo-AEGIS/phase III[60]	377/cT2-3N0-3M0/esophagus GEJ/adenocarcinoma	E: carboplatin, paclitaxel + 41.4 Gy radiation OR C: epirubicin, cisplatin/oxaliplatin, 5-FU/capecitabine or docetaxel, oxaliplatin, leucovorin, 5-FU ANDsurgery (all arms)	OS rate: 56% experimental vs 57% 3-yr OS HR 1.02, (95%CI: 0.74-1.42)

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.