Perioperative Chemotherapy Improves Outcomes in Operable Gastric Cancers

ORLANDO-Chemotherapy given before and after surgery is better than surgery alone for operable gastric and lower esophageal cancers, David Cunningham, MD, reported (abstract 4001). Dr. Cunningham of The Marsden Hospital, Surrey, UK, presented data from the MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) trial, after a median follow-up of 3 years. Researchers in this trial compared progression- free and overall survival for 503 patients with operable cancers of the stomach, lower esophagus, or the gastroesophageal junction. Patients were randomized to undergo surgery alone or surgery plus preoperative and postoperative chemotherapy with epirubicin, cisplatin, and fluorouracil (5- FU) given by continuous infusion (ECF). Chemotherapy Up Front Is a 'Good Idea' This trial was designed to determine whether the benefit seen with ECF in advanced esophagogastric cancer, translates into a survival advantage in operable disease. Patients with operable adenocarcinoma of the stomach, gastroesophageal junction, or lower esophagus were randomized to receive perioperative chemotherapy (CSC arm, n = 250) or surgery alone (S arm, n = 253). Patients in the CSC arm received three preoperative and three postoperative cycles, 3 weeks apart, of epirubicin (50 mg/m² IV bolus), cisplatin (60 mg/m² infusion), and 5-FU (200 mg/m²/day by continuous infusion). "Giving chemotherapy up front in this disease overcomes the problem of administering chemotherapy after surgery. Recovery after gastric sur- gery is often prolonged so that many patients may not actually receive postoperative chemotherapy. After surgery, the patient needs 2-3 months to recover, and many don't actually get postoperative chemotherapy," Dr. Cunningham reported.

Survival Advantage "Perioperative chemotherapy improves 5-year survival from 23% to 36%, similar to results with chemoradiotherapy after surgery. This is likely to become the preferred option in Europe," Dr. Cunningham said. Five years after diagnosis, 36% of the chemotherapy group was still alive, compared with 23% of the surgery group (see Table 1). The survival hazard ratio (HR) is 0.75, 95% CI (0.60, 0.93), P = .009. Progression-free survival was also significantly prolonged. "In operable gastric and lower esophageal cancer, perioperative chemotherapy with ECF leads to downsizing of the primary tumor, significantly improves progression-free survival, and significantly improves overall survival," Dr. Cunningham concluded. "This approach should be considered one of the standard treatment options for patients with these cancers." During the discussion, there were questions about how this approach compares with surgery followed by chemoradiotherapy, the approach usually performed in the United States. Dr. Cunningham said that outcomes are similar and that he sees the perioperative strategy as offering another option for treating these cases. Robert J. Mayer, MD, of Dana- Farber Cancer Institute, Boston, MA, who was the discussant for this paper, raised the question of whether the results would have been enhanced or compromised by the addition of preoperative chemoradiotherapy to the MAGIC regimen. However, it is difficult to directly compare the results of both studies as patients for MAGIC were enrolled in the study at diagnosis whereas patients for the US Intergroup study were enrolled only after they had undergone potentially curative surgery.