Perioperative chemotherapy in operable gastric and lower oesophageal cancer: Final results of a randomised, controlled trial (the MAGIC trial, ISRCTN 93793971)

4001 Background: Epirubicin, Cisplatin and infused 5-FU (ECF) shows significant benefit in advanced oesophagogastric cancer, particularly locally advanced disease. This trial was designed to determine whether this effect translates into a survival advantage in operable disease. Methods: Patients with operable adenocarcinoma of the stomach, oesophagogastric junction or lower oesophagus were randomised to perioperative chemotherapy (CSC arm) or surgery alone (S arm). In the CSC arm, chemotherapy comprised three pre-operative and three post-operative cycles, 3 weeks apart, of E 50mg/m2 IV bolus, C 60mg/m2 infusion and 5-FU 200mg/m2/day continuous infusion. The trial was powered (2α=5%, 1-β=90%) to detect a 15% increase in 5-year survival (∼250 events required), with pre-planned analysis with another European trial of the same design, collectively giving ∼90% power to detect a 10% increase in survival. The latter trial closed early, therefore to increase power to detect a 10% increase from MAGIC alone, the final analysis was deferred until sufficient events had occurred to give at least 70% power (∼320 deaths) to detect a hazard ratio (HR) of 0.75, equivalent to an absolute difference in survival of approximately 10% at 2 and 5 years. Results: Between 1994 and 2002, 503 patients (250 CSC, 253 S) were randomised; 74% gastric, 11% oesophago-gastric junction and 15% lower oesophagus. Initial analysis (ASCO 2003) demonstrated statistically significant differences in favour of CSC with respect to curative resection rate, resected tumour diameter and, for gastric and junctional patients, T stage. As of 12/2004, with median follow-up >3 years and 90% of patients followed to death or >2 years, 319 deaths have occurred, (149 CSC, 170 S). The survival HR is 0.75, 95% CI (0.60, 0.93), p=0.009; 5 year survival rates for CSC and S are 36% (30%, 43%) and 23% (17%, 29%) respectively. Progression-free survival was also significantly prolonged; HR 0.66 (0.53, 0.81), p=0.0001. Conclusions: Perioperative chemotherapy significantly improves resectability, progression-free and overall survival in operable gastric and lower oesophageal cancer. No significant financial relationships to disclose.