Results from the Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial in the United Kingdom suggest that standard treatment for operable gastric cancers should be changed. According to MAGIC researcher William Allum, MD, consultant surgeon at Royal Marsden Hospital in London, chemotherapy before surgery is at least as effective as the U.S. standard of care, surgery followed by chemoradiotherapy, and is easier for patients to tolerate.
   "We are recommending that this (MAGIC regimen) be adopted as the standard of care," Dr. Allum told the American College of Surgeons Clinical Congress. "This combination of treatment translates into increased disease-free time to progression and increased survival. Giving chemotherapy before surgery produces a better biological effect. Nearly half of patients are not fit enough to undergo chemoradiotherapy following surgery."
   The MAGIC regimen, combination therapy with epirubicin, cisplatinum, and 5-flurorcil (ECF) grew out of earlier studies showing improved survival for patients who had inoperable gastric tumors. In many patients, Dr. Allum noted, tumors that were previously inoperable due to size or proximity to vital structures regressed sufficiently to allow resection. The MAGIC trial was designed to see if the same beneficial tumor shrinkage effect could be translated into patients with tumors that were operable when diagnosed.
   The question was particularly useful, Dr. Allum noted, because the incidence of gastric cancers is trending up in the United States, the European Union, Japan, and most other countries with adequate data to track the disease. The problem, he explained, is that cancers of the stomach and the lower third of the esophagus produce few specific symptoms in the early stages.
   Five-year survival is 93% for stage I gastric cancers, he noted, but physicians seldom diagnose stage I disease. Survival falls to 69% for stage II disease and 28% for stage III tumors.
   "The majority of patients present with advanced disease," Dr. Allum said. "Surgery alone is not especially helpful and outcomes from surgery alone are not particularly encouraging. There is a real need to combine surgery with other modalities."
   The MAGIC design included two randomized arms, traditional surgery and an experimental arm of ECF plus surgery. The trial enrolled 503 patients between 1994 and 2002. Recruitment was slow, Dr. Allum said, because both patients and surgeons were reluctant to accept randomization to the chemotherapy arm.
   "The reaction was almost always 'cut it out before it gets any larger,'" he explained.
   The delay between randomization and surgery averaged 13 days, Dr. Allum continued, but the ECF protocol required a 99-day delay for treatment before surgery. In retrospect, he added, it was clear that tumors were shrinking, not growing, during the three-month delay, but that result could not be anticipated during the accrual stage.
   Surgery was considered curative in 79% of patients given ECF plus surgery compared to 69% for those who received surgery alone. Postop complications and the rate of death following surgery was similar for the two groups.
   The maximum diameter of excised tumors was 3 cm for the ECF group compared to 5 cm for the surgery-only group. Pathological examination indicated that the ECF-treated tumors were more likely to be limited to the inner layers of the stomach and less likely to involve lymph nodes.
   Half of the patients in the trial have been followed for at least three years and 90% have been followed for at least two years or until death. The hazard ratio for progression-free survival was 0.66 in the ECF group compared to the surgery-only group and the hazard ratio for overall survival was 0.75. Researchers found that ECF offered patients a 9% survival advantage at two years and a 13% advantage at five years. Both improvements are statistically significant, Dr. Allum said.