ORLANDO -- Adjuvant chemotherapy with S-1, an oral prodrug of 5-fluorouracil (5-FU), improved survival compared with surgery alone, according to results of a phase III trial of 1,059 gastric cancer patients here reported here.
ORLANDO, Jan. 19 -- Adjuvant chemotherapy with S-1, an oral prodrug of 5-fluorouracil, improved gastric cancer survival compared with surgery alone, according to results of a Japanese phase III trial reported here.
The trial of 1,059 patients was halted early on the recommendation of a data safety monitoring board on the basis of an analysis that showed a survival advantage, said Mitsuru Sasako, M.D., of the National Cancer Center Hospital in Tokyo at a gastrointestinal cancer symposium sponsored by several societies.
Three-year overall survival was 80.5% for 529 patients in the S-1 plus surgery arm versus 70.1% for 530 patients in the surgery-alone arm (P=0.0024).
S-1 is available in Japan and Korea, but not in the U.S., although Sanofi-Aventis said it was developing the drug for marketing here.
The study recruited patients from October 2001 through December 2004. All patients had negative margins following resection for treatment of stage II/III gastric cancer.
Five hundred and seventeen patients were randomized to S-1 80-120 mg/day for four weeks, followed by two-weeks off therapy, with the cycle repeated for a year. Treatment was initiated within 45 days of surgery. The primary endpoint was overall survival.
An interim analysis performed in June 2006 using survival data as of December 2005 found that S-1 was associated with a 43% reduction in mortality (HR 0.57, 95% CI, 0.40-0.81, P=0.0016). On the basis of that favorable analysis, the data safety monitoring board recommended that the trial be stopped.
Dr. Sasako said the findings were also significant because the survival benefit was achieved with "a single agent that is cheaper and less toxic that chemotherapy regimens commonly used in the U.S. and Europe."
In the U.S. a number of strategies are used for such patients, including pre- and post-operative Ellence (epirubicin), Platinol (cisplatin), and 5-FU.
William Blackstock, M.D., of North Carolina Baptist Hospital in Winston-Salem, who moderated a press briefing during which Dr. Sasako presented his data, agreed, "Treatment with S-1 is potentially less expensive and less toxic than current treatments."
But he noted that the surgery performed in Japan is more extensive than procedures usually performed in the United States, which may limit generalizing the Japanese results to the U.S. or Europe.
Dr. Sasako said that less than 1% of the patients randomized to S-1 reported Grade 4 toxicities.
The GI Cancer Symposium is co-sponsored by the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, the American Gastroenterological Association Institute, and the Society of Surgical Oncology.