Neoadjuvant chemotherapy compared with surgery alone for locally advanced cancer of the stomach and cardia: European Organisation for Research and Treatment of Cancer randomized trial 40954.
OBJECTIVE
Patients with locally advanced gastric cancer benefit from combined pre- and postoperative chemotherapy, although fewer than 50% could receive postoperative chemotherapy. We examined the value of purely preoperative chemotherapy in a phase III trial with strict preoperative staging and surgical resection guidelines.


METHODS
Patients with locally advanced adenocarcinoma of the stomach or esophagogastric junction (AEG II and III) were randomly assigned to preoperative chemotherapy followed by surgery or to surgery alone. To detect with 80% power an improvement in median survival from 17 months with surgery alone to 24 months with neoadjuvant, 282 events were required.


RESULTS
This trial was stopped for poor accrual after 144 patients were randomly assigned (72:72); 52.8% patients had tumors located in the proximal third of the stomach, including AEG type II and III. The International Union Against Cancer R0 resection rate was 81.9% after neoadjuvant chemotherapy as compared with 66.7% with surgery alone (P = .036). The surgery-only group had more lymph node metastases than the neoadjuvant group (76.5% v 61.4%; P = .018). Postoperative complications were more frequent in the neoadjuvant arm (27.1% v 16.2%; P = .09). After a median follow-up of 4.4 years and 67 deaths, a survival benefit could not be shown (hazard ratio, 0.84; 95% CI, 0.52 to 1.35; P = .466).


CONCLUSIONS
This trial showed a significantly increased R0 resection rate but failed to demonstrate a survival benefit. Possible explanations are low statistical power, a high rate of proximal gastric cancer including AEG and/or a better outcome than expected after radical surgery alone due to the high quality of surgery with resections of regional lymph nodes outside the perigastic area (celiac trunc, hepatic ligament, lymph node at a. lienalis; D2).
Klinikum rechts der Isar, Chirurgische Klinik der TU München, Ismaningerstr. 22, D-81675 München, Germany. schuhmacher@chir.med.tu-muenchen.de
Christoph
C
Schuhmacher
Stephan
S
Gretschel
Florian
F
Lordick
Peter
P
Reichardt
Werner
W
Hohenberger
Claus F
CF
Eisenberger
Cornelie
C
Haag
Murielle E
ME
Mauer
Baktiar
B
Hasan
John
J
Welch
Katja
K
Ott
Arnulf
A
Hoelscher
Paul M
PM
Schneider
Wolf
W
Bechstein
Hans
H
Wilke
Manfred P
MP
Lutz
Bernard
B
Nordlinger
Eric
E
Van Cutsem
Jörg R
JR
Siewert
Peter M
PM
Schlag
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002299:Cardia / Q000473:pathology / Q000601:surgery; D003131:Combined Modality Therapy; D013505:Digestive System Surgical Procedures; D018572:Disease-Free Survival; D004943:Esophagogastric Junction / Q000187:drug effects / Q000473:pathology / Q000601:surgery; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*
D000970:Antineoplastic Agents