Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.
BACKGROUND
A regimen of epirubicin, cisplatin, and infused fluorouracil (ECF) improves survival among patients with incurable locally advanced or metastatic gastric adenocarcinoma. We assessed whether the addition of a perioperative regimen of ECF to surgery improves outcomes among patients with potentially curable gastric cancer.


METHODS
We randomly assigned patients with resectable adenocarcinoma of the stomach, esophagogastric junction, or lower esophagus to either perioperative chemotherapy and surgery (250 patients) or surgery alone (253 patients). Chemotherapy consisted of three preoperative and three postoperative cycles of intravenous epirubicin (50 mg per square meter of body-surface area) and cisplatin (60 mg per square meter) on day 1, and a continuous intravenous infusion of fluorouracil (200 mg per square meter per day) for 21 days. The primary end point was overall survival.


RESULTS
ECF-related adverse effects were similar to those previously reported among patients with advanced gastric cancer. Rates of postoperative complications were similar in the perioperative-chemotherapy group and the surgery group (46 percent and 45 percent, respectively), as were the numbers of deaths within 30 days after surgery. The resected tumors were significantly smaller and less advanced in the perioperative-chemotherapy group. With a median follow-up of four years, 149 patients in the perioperative-chemotherapy group and 170 in the surgery group had died. As compared with the surgery group, the perioperative-chemotherapy group had a higher likelihood of overall survival (hazard ratio for death, 0.75; 95 percent confidence interval, 0.60 to 0.93; P=0.009; five-year survival rate, 36 percent vs. 23 percent) and of progression-free survival (hazard ratio for progression, 0.66; 95 percent confidence interval, 0.53 to 0.81; P<0.001).


CONCLUSIONS
In patients with operable gastric or lower esophageal adenocarcinomas, a perioperative regimen of ECF decreased tumor size and stage and significantly improved progression-free and overall survival. (Current Controlled Trials number, ISRCTN93793971 [controlled-trials.com].).
Cunningham
David
D
Department of Medicine, Royal Marsden Hospital, Sutton , Surrey, United Kingdom. david.cunningham@rmh.nhs.uk
Allum
William H
WH
Stenning
Sally P
SP
Thompson
Jeremy N
JN
Van de Velde
Cornelis J H
CJ
Nicolson
Marianne
M
Scarffe
J Howard
JH
Lofts
Fiona J
FJ
Falk
Stephen J
SJ
Iveson
Timothy J
TJ
Smith
David B
DB
Langley
Ruth E
RE
Verma
Monica
M
Weeden
Simon
S
Chua
Yu Jo
YJ
MAGIC Trial Participants
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D016629:Esophagectomy; D004943:Esophagogastric Junction / Q000601:surgery; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005743:Gastrectomy; D006801:Humans; D008297:Male; D008875:Middle Aged; D019990:Perioperative Care; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery*; D015996:Survival Rate
D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil