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Hope for Patients with Gastric Cancer

An increase in the survival rate was noted among patients randomized to surgery with perioperative chemotherapy compared with those who received surgery alone.

In the U.S., most patients with cancers of the stomach and lower esophagus present with locally advanced disease, and cure is rare. In previous studies, adjuvant chemotherapy has failed to provide a significant survival advantage compared with surgery alone for gastric cancer. In this European multicenter study (called MAGIC), investigators randomized 503 patients with resectable adenocarcinomas (of the stomach, esophagogastric junction, or lower esophagus) to perioperative chemotherapy plus surgery or to surgery alone. Patients in the chemotherapy arm received three preoperative and three postoperative cycles of intravenous epirubicin and cisplatin on day 1 and continuous intravenous infusion of 5-fluorouracil (ECF) for the entire 21-day cycle.

Postoperative complications were similar in both groups (about 45%). Chemotherapy generally was well tolerated, with about a quarter of patients experiencing neutropenia. After surgery, no clinically significant increases in grade 3 or 4 toxicities associated with chemotherapy were noted. The median maximum diameter of the resected tumors was smaller in the chemotherapy group than in the surgery-alone group (3 cm vs. 5 cm; P<0.001). A greater proportion of patients in the chemotherapy group than in the surgery-alone group had stage T1 or T2 tumors (51.7% vs. 36.8%; P=0.002). Significantly fewer patients in the chemotherapy group had advanced nodal disease (84.4% had N0 or N1 vs. 70.5% in the surgery-alone group).

At a median follow-up of 49 months, patients who received perioperative chemotherapy had a significantly higher chance of survival (hazard ratio for death, 0.75; 95% confidence interval, 0.60–0.93; P=0.009; 5-year survival rate, 36% vs. 23%) and of progression-free survival (HR for progression, 0.66; 95% CI, 0.53–0.81; P<0.001) compared with patients who received surgery alone.

Comment: The MAGIC trial represents a landmark study in gastric cancer, as it is the first trial to demonstrate a survival benefit for pre- and postoperative chemotherapy compared with surgery alone. These results contrast with prior studies of postoperative chemotherapy, in which survival was not improved. Most U.S. patients undergo surgery first, and postoperative chemoradiotherapy likely will remain the predominant strategy for some time. From a surgical perspective, preoperative chemotherapy downsizes the primary tumor, reduces associated nodal disease, and increases the chances of resectability with negative margins. Whether this protocol will represent an alternative or a complement to the current U.S. standard of postoperative chemoradiotherapy remains to be established, but an absolute increase in 5-year survival of 13% is a significant advance for the treatment of this disease.

The current CALGB trial 80101 employs the ECF regimen used in the MAGIC trial, but only postoperatively, in combination with 5-fluorouracil and radiotherapy. Addition of preoperative chemotherapy to the U.S. practice of postoperative chemoradiotherapy should influence design of future adjuvant trials in gastric cancer.

— Henry Mark Kuerer, MD, PhD, FACS, and David H. Ilson, MD, PhD

Published in Journal Watch Oncology and Hematology October 16, 2006

Citation(s):

Cunningham D et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006 Jul 6; 355:11-20.

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