Postoperative chemotherapy with the experimental agent S-1 improves overall survival of patients with gastric cancer compared with surgery alone, according to a presentation of a Japanese phase III study at the 2007 Gastrointestinal Cancers Symposium.

“This is the first phase III study to compare S-1 chemotherapy following surgery to surgery alone,” said Mitsuro Sasako, MD, Professor of Surgery and Deputy Director of the National Cancer Center Hospital in Tokyo, Japan and the study’s lead author. “The findings are significant because they showed improved survival with a single chemotherapy agent?one that is cheaper and has lower toxicity than adjuvant chemotherapy regimens commonly used in North America and Europe.”

Current therapy options depend on surgery, sometimes followed by chemotherapy, radiation, or a combination of the two. Although postoperative chemotherapy has shown benefit in some patients, it is unclear which chemotherapy drugs are the most effective.

In the current study, 1,059 patients were randomized to receive S-1 chemotherapy following surgery (529 patients) or curative D2 surgery alone (530 patients), the current standard treatment in Japan. Eligibility criteria included R0 resection, pathological stage II/III (Japanese Classification), age between 20 and 80 years, no prior adjuvant treatment, adequate organ function. Patients were randomized to S-1 (80-120mg/day according to body surface, 4 weeks administration with 2 weeks off in each course, starting within 45 days of surgery until 1 year after surgery,) or surgery alone.

Primary end point was overall survival. When the one-year interim analysis was done, the difference in survival was sufficient that the trial was stopped. At three years, overall survival for patients who received S-1 was 80.5 percent compared with 70.1 percent for patients who received only surgery.

Side effects of chemotherapy were rare and included anorexia (6.0 percent of S-1 group had severe symptoms versus 2.1 percent of surgery group) and some blood-related toxicities.

S-1 belongs to the drug class called oral fluoropyrimidines. It is also being evaluated in clinical trials as a treatment for other gastrointestinal cancers including colorectal and pancreatic tumors.