Perioperative chemotherapy in operable gastric and lower oesophageal cancer: A randomized, controlled trial (the MAGIC trial, ISRCTN 9379397)

Reviewer: Tracy d'Entremont, MD
Last Modified: June 2, 2003

Presenter: W. Allum
Presenter's Affiliation: Epsum General Hospital; Surrey, UK
Type of Session: Scientific


  • The combination of Epirubicin, Cisplatin and infusional 5-FU (ECF) has demonstrated increased RR and statistically significant benefit in advanced oesophagogastric cancer
  • This trial was designed to determine if this benefit could be translated into the adjuvant setting for resectable disease.

Materials and Methods

  • Patients with adenocarcinoma of the stomach, gastroesophageal junction or lower esophagus, of at least stage II, who were felt based on a combination of CT scan and EUS to be suitable for curative resection were randomized to surgery alone or perioperative chemotherapy followed by surgery.
  • The chemotherapy consisted of both neoadjuvant and adjuvant chemotherapy.
  • Patients assigned to chemotherapy were treated with Epirubicin 50mg/m2 i.v. bolus on d1, cisplatin 60mg/m2 iv infusion over 4 hours on d1, and 5-FU 200mg/m2/d by continuous i.v. infusion d1-21 of a 21 day cycle.
  • Patients were given 3 preoperative courses of chemotherapy and were then given another 3 courses post-operatively (scheduled to begin 6-12 weeks after surgery).
  • The type of surgery was left to the discretion of the surgeon, however some guidelines were outlined. Such as the recommendation for at least 3 cm margins, for dissection along the greater and lesser curvatures and for at least a level one node dissection.
  • At the conclusion of the surgery, the surgeons were asked to classify the operative result as either curative or palliative.
  • The primary outcome was Overall Survival. The study was powered to detect a 15% increase in 5-yr survival from 23% to 38%. For 90% power, 500 patients were required.
  • It took almost 8 years to accrue to this trial which may make the data less generalizable.


  • 503 patients were enrolled. The median age was 62. 75% of patients were male. 68% had excellent performance status of WHO=0.
  • 91% of patients completed the neoadjuvant portion of the trial.
  • 55% of patients started the post-operative chemotherapy portion of the trial.
  • 40% of patients completed all 6 planned cycles of chemotherapy.
  • The reason stated for failure to complete the prescribed treatment were most commonly death, progression, post-operative complications or patient request.
  • The percent of patients able to have a curative resection was significantly higher in the treated population (79% vs. 69%)
  • Patients appeared to be adequately downstaged according to T status with 51% of treated patients having T1/2 tumors resected compared with only 36% of untreated patients.
  • Interestingly enough the nodal stage was not statistically downstaged with 80% of treated patients having a N0/1 resection versus 71% of untreated patients.
  • Post operative complications were identical in both arms as was mortality in the first 30 days. Deaths overall in both groups were not significantly different and there were no toxic treatment related deaths.
  • The progression free survival was superior in the chemotherapy group with a HR=0.7.
  • Overall survival demonstrated a trend toward significance but failed to demonstrate a statistically significant improvement.
  • The difference in median survival between the two groups was 24 mos an 19 mos respectively. The 2-yr OS was 48% and 40% respectively.

Author's Conclusions

  • Preoperarative chemotherapy with ECF allows for an increased number of curative resections.
  • PFS was improved in the treatment group.
  • There was a trend towards improved OS.

Clinical/Scientific Implications

  • We must consider the results of this trial in the setting of other completed adjuvant gastric trials.
  • For example, in INT-0116 which was published last year, the DFS in the surgery alone arm was comparable at 19 mos, but that treatment group had an improved DFS of 30 mos which is longer than reported in this MAGIC trial.
  • And despite the fact that more patients in the INT-0116 trial had positive nodes and of them more had greater than 4 positive nodes, the 2 yr survival rate in that study was higher than in the MAGIC trial (58% vs 48%)
  • The INT-0116 trial demonstrated the utility in postoperative combined modality therapy of chemo + XRT. Before we can change the standard of care in favor of ECF, we need to ask ourselves whether some of these patients should have been offered XRT.
  • Potentially the next trial that we should design would be one that offers neoadjuvant chemotherapy followed by randomization to chemotherapy alone or chemo + XRT after curative resection.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.