Cisplatin plus the novel oral fluoropyrimidine S-1 significantly improves survival of patients with advanced gastric cancer compared with S-1 alone, according to results of a phase III study presented at the annual meeting of the American Society of Clinical Oncology.

"This study demonstrates that the combination of S-1 and cisplatin brings to the patient with advanced gastric cancer an acceptable benefit/risk ratio," said Hiroyuki Narahara, MD, presenter and study investigator. "The results confirm previous data we've seen in Japan, where S-1 has been on the market for the treatment of gastric cancer for eight years now."

The SPIRITS study, a multicenter, open-label trial in Japan, randomized 305 patients with unresectable or recurrent advanced gastric cancer who had never been treated with chemotherapy to receive oral S-1 twice daily for 28 days followed by a 14-day rest period, or oral S-1 twice daily for 21 days plus intravenous cisplatin on the eighth day of treatment, followed by the 14-day rest period. The dose of S-1 was the same for both groups, 40 mg/m2 twice daily.

The primary endpoint was overall survival. Secondary endpoints included response rate, time to treatment failure, and toxicity. The trial was designed to have 90 percent power to detect an improvement in median overall survival from 8 to 12 months.

With two-year follow-up, the combination reduced the risk of death by 22.6 percent over S-1 alone: Overall survival was significantly higher in the S-1/cisplatin combination arm compared with S-1 alone (median 13 months versus 11 months). Overall response rate was also significantly better among patients treated with S-1 and cisplatin (54 percent versus 31.1 percent).

There were more grade 3/4 hematological and gastro-intestinal (anorexia/nausea) toxicities when cisplatin was combined with S-1, and there were much lower incidences of the same side effects with S-1 alone.