Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer
David Cunningham, M.D., William H. Allum, M.D., Sally P. Stenning, M.Sc., Jeremy N. Thompson, M.Chir., Cornelis J.H. Van de Velde, M.D., Ph.D., Marianne Nicolson, M.D., J. Howard Scarffe, M.D., Fiona J. Lofts, Ph.D., Stephen J. Falk, M.D., Timothy J. Iveson, M.D., David B. Smith, M.D., Ruth E. Langley, M.D., Ph.D., Monica Verma, M.Sc., Simon Weeden, M.Sc., Yu Jo Chua, M.B., B.S., for the MAGIC Trial Participants
Background A regimen of epirubicin, cisplatin, and infused fluorouracil(ECF) improves survival among patients with incurable locallyadvanced or metastatic gastric adenocarcinoma. We assessed whetherthe addition of a perioperative regimen of ECF to surgery improvesoutcomes among patients with potentially curable gastric cancer.
Methods We randomly assigned patients with resectable adenocarcinomaof the stomach, esophagogastric junction, or lower esophagusto either perioperative chemotherapy and surgery (250 patients)or surgery alone (253 patients). Chemotherapy consisted of threepreoperative 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 intravenousinfusion of fluorouracil (200 mg per square meter per day) for21 days. The primary end point was overall survival.
Results ECF-related adverse effects were similar to those previouslyreported among patients with advanced gastric cancer. Ratesof postoperative complications were similar in the perioperative-chemotherapygroup 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 advancedin the perioperative-chemotherapy group. With a median follow-upof four years, 149 patients in the perioperative-chemotherapygroup and 170 in the surgery group had died. As compared withthe surgery group, the perioperative-chemotherapy group hada 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-freesurvival (hazard ratio for progression, 0.66; 95 percent confidenceinterval, 0.53 to 0.81; P<0.001).
Conclusions In patients with operable gastric or lower esophagealadenocarcinomas, a perioperative regimen of ECF decreased tumorsize and stage and significantly improved progression-free andoverall survival. (Current Controlled Trials number, ISRCTN93793971.)
Source Information
From the Departments of Medicine (D.C., Y.J.C.) and Surgery (W.H.A., J.N.T.), Royal Marsden Hospital, Surrey and London; the Medical Research Council Clinical Trials Unit, Cancer Group, London (S.P.S., R.E.L., M.V., S.W.); the Department of Oncology, Aberdeen Royal Infirmary, Aberdeen (M.N.); the Department of Medical Oncology, Christie Hospital, Manchester (J.H.S.); the Department of Medical Oncology, St. George's Hospital, London (F.J.L.); the Department of Oncology, Bristol Haematology and Oncology Centre, Bristol (S.J.F.); the Medical Oncology Unit, Southampton General Hospital, Southampton (T.J.I.); and the Clatterbridge Centre for Oncology, Liverpool (D.B.S.) — all in the United Kingdom; and the Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands (C.J.H.V.V.).
Address reprint requests to Prof. Cunningham at the Department of Medicine, Royal Marsden Hospital, Downs Rd., Sutton, Surrey SM2 5PT, United Kingdom, or at david.cunningham{at}rmh.nhs.uk.
Treatment of Gastric Cancer
Singh J., Williamson S. K., Malani A. K., Harewood G. C., Fielding J., Peake D., Jani K., Boot H., Jansen E. P.M., Cats A., Lloyd D. A.J., Gabe S. M., Cunningham D., Allum W. H., Stenning S. P.
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N Engl J Med 2006;
355:1386-1388, Sep 28, 2006.
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