Table 4.

Clinical trials comparing chemotherapy regimens

Study name/phase	Size/stage/primary tumor location/histology	Intervention	Primary endpoint
ECOG E7296/phase II[74]	38 patients/T2N1-2, T3-4Nany/stomach 45% GEJ 55%/adenocarcinoma 95% SCC 5%	E: neoadjuvant cisplatin, paclitaxel → surgery → 5-FU/LV + 45 Gy radiation	Tolerability: 66% grade 3/4 toxicities during neoadjuvant treatment 7.9% completed per protocol treatment
CALGB 80803/ Phase II[76]	241 patients/T1N1-3M0, T2-4NanyM0 (resectable)/esophagus GEJ adenocarcinoma	E1: induction oxaliplatin, 5-FU/LV OR E2: induction carboplatin, paclitaxelAND PET scan → non-responders change chemotherapy arm, responders continue → chemotherapy + 50,4 Gy radiation → surgery (both arms)	pCR: 18% [95%CI (7.5-33.5)] experimental 1; and 20% [95%CI (10, 33.7)] experimental 2 of PET non-responders who switched chemotherapy arm achieved pCR
E1201/phase II[77]	81 patients/II-Iva/esophagus GEJ/adenocarcinoma	E1: preoperative cisplatin, irinotecan + 45 Gy radiation → surgery → cisplatin, irinotecan OR E2: preoperative cisplatin, paclitaxel + 45 Gy radiation → surgery → cisplatin, paclitaxel	pCR: 15.4%, exact, unadjusted 90% binomial CI: 6.9%-28.1% experimental 1 and 16.7%, exact, unadjusted 90% binomial CI: 8.1%-29.0% experimental 2 achieved pCR
RTOG-0114/phase II[78]	73 patients/IB-IIIB/stomach/adenocarcinoma	Gastrectomy (both arms) AND E1: cisplatin, paclitaxel, 5-FU + 45 Gy radiation OR E2: cisplatin, paclitaxel + 45 Gy radiation	DFS rate: E1 closed early due to toxicity (14.6 m DFS) 52% (95%CI: 36%-68%) experimental 2 2-yr DFS
NCCTG N0849/phase II[79]	42 patients/T3-4N0, TanyN+/III-IVA/esophagus/55% GEJ 40% cardia 3.6% adenocarcinoma	E: induction docetaxel, oxaliplatin, capecitabine OR C: no induction AND oxaliplatin, 5-FU + 50.4 Gy radiation → surgery (both arms)	pCR: 33% experimental and 48% control achieved pCR
CALGB 80101/phase III[80]	546 patients/IB-IV (M0)/stomach 78% (4% proximal gastric, 41% distal gastric, 15% stomach NOS, 17% multicentric) GEJ 22%/adenocarcinoma	Surgery (both arms) AND E: epirubicin, cisplatin, 5-FU → 5-FU + 45 Gy radiation → chemotherapy OR C: 5-FU/LV → 5-FU + 45 Gy radiation → chemotherapy	OS rate: 44% control vs 44% experimental multivariate HR 0.98 (95%CI: 0.78-1.24, P = 0.69) 5-yr OS
PRODIGE5/ACCORD17 phase II/III[81]	259 patients/I-IVA/esophagus/adenocarcinoma 14% SCC 86%	E: oxaliplatin, 5-FU/LV + 50 Gy radiation OR C: cisplatin, 5-FU + 50 Gy radiation	mPFS: 9.7 m experimental vs 9.4 m control HR 0.93 (95%CI: 0.70-1.24, P = 0.64)

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; PET: Positron emission tomography; GEJ: Gastroesophageal junction; CRT: Chemoradiation; AEG: Adenocarcinomas of the esophagogastric junction.