ORLANDO — Gastric cancer patients who received perioperative chemotherapy showed a 13% absolute improvement in 5-year survival in a large phase III trial sponsored by the United Kingdom's Medical Research Council.
Of the patients who received chemotherapy before and after surgery, 36% were alive 5 years after diagnosis, whereas only 23% of a control group randomized to surgery alone lived that long, investigator David Cunningham, M.D., reported at the annual meeting of the American Society of Clinical Oncology.
The chemotherapy regimen downstaged primary tumors and signif-icantly improved progression-free survival as well, said Dr. Cunningham of the Royal Marsden Hospital in Surrey, England. He reported recurrences in 62% of the control group but in only 42% of patients who received perioperative chemotherapy.
The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial enrolled 503 patients with operable cancer of the stomach and lower esophagus from July 1994 to April 2002. The trial randomized 253 patients to surgery alone and 250 to receive surgery plus three preoperative and three postoperative cycles of chemotherapy.
The chemotherapy regimen contained an intravenous bolus of 50 mg/m
Fewer patients in the chemotherapy arm proceeded to surgery: 219 patients (about 88%) vs. 240 patients (95%) in the control group. Yet more chemotherapy patients had operations that were deemed curative: 169 patients (about 79%) compared with 166 patients (about 70%) who had no chemotherapy.
Postoperative deaths (6%) and complications (46%) were the same for both groups, as was the median postoperative hospital stay (13 days).
Postsurgery pathology showed the chemotherapy patients had a smaller maximum tumor diameter (median 3 cm vs. 5 cm in the control group). The chemotherapy patients with gastric tumors were more likely to have less advanced disease: 52% were classified as T1 or T2 vs. 38% of the control group. They were also less likely to have more advanced nodal status: 16% were classified as N3 or N4 vs. 29% of the controls.
Median survival was calculated as 24 months with chemotherapy and 20 months with surgery alone. The unadjusted hazard ratio for death was 0.75 in the chemotherapy arm. Progression-free survival was also superior, with a hazard ratio of 0.66 favoring chemotherapy.
Survival results were based on an intent-to-treat analysis at a median follow-up greater than 3 years. In all, 90% of patients were followed 2 or more years or until death.
In response to an audience question, Dr. Cunningham declined to claim that the trial established perioperative chemotherapy as a new standard. Surgery alone has been standard in Europe, he said, whereas postoperative chemoradiation has been common in the United States since its benefits were reported in another standardized trial (N. Engl. J. Med. 2001;345:725–30).
“It is difficult to compare and contrast the two different strategies, but I think what the study does do is offer us the option of two different strategies for patients with this disease—either perioperative chemotherapy or surgery and then postoperative chemoradiation,” he said. “And maybe combining those strategies can improve outcomes.”
Dr. Cunningham rejected a suggestion that patients in the MAGIC trial's control arm had poorer survival than did patients in other adjunctive therapy trials. He said these groups could not be compared, because the MAGIC trial enrolled “all comers,” whereas adjunctive therapy trials enroll only patients who have had successful operations.
“There hasn't been much improvement in outcome [for gastric cancer patients until now], but with these multimodalities we are hoping there will be,” Dr. Cunningham told this newspaper. He described the current outlook for patients with non-colorectal gastrointestinal cancers as “pretty grim,” but predicted that current investigations would soon lead to “massive” improvement.
In a discussion of the MAGIC trial, Robert J. Mayer, M.D., said the results “are convincing, validating the concept of perioperative chemotherapy.” What remains unclear, said Dr. Mayer, director of the center for gastrointestinal oncology at the Dana-Farber Cancer Institute in Boston, is which chemotherapy regimen is the best combination, not only for perioperative chemotherapy but also for postoperative chemoradiation.
