Taiho and sanofi-aventis announced the results of a phase III trial in advanced gastric cancer, which shows that the combination of the investigational oral fluoropyrimidine S-1 with cisplatin significantly reduces the risk of death by 22.6% (hazard ratio = 0.774; 95% confidence interval = 0.608-0.985) over S-1 alone.
Taiho and sanofi-aventis announced the results of a phase III trial in advanced gastric cancer, which shows that the combination of the investigational oral fluoropyrimidine S-1 with cisplatin significantly reduces the risk of death by 22.6% (hazard ratio = 0.774; 95% confidence interval = 0.608-0.985) over S-1 alone. Findings from the SPIRITS study, a Japanese multicenter, randomized, open label phase III trial, were presented at the 43rd Annual Meeting of the American Society of Clinical Oncology (ASCO).
The overall survival with a 2-year follow-up was significantly higher in the S-1/cisplatin combination arm over S-1 alone (median of 13 vs 11 months, respectively, P = .036). The overall response rate is also significantly better among patients treated with S-1 and cisplatin (54% of patients treated with the combination responded to treatment compared with 31.1% with S-1 alone, P = .001).
There were more grade 3/4 hematologic 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.
"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 Dr. Hiroyuki Narahara, 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 8 years now."
About the SPIRITS Study
The SPIRITS study is part of an investigational ongoing program testing S-1 in combination with different anticancer drugs in advanced gastric cancer. This study was designed to evaluate the efficacy of S-1 combined with cisplatin compared to S-1 alone in patients with unresectable or recurrent advanced gastric cancer who have never been treated with chemotherapy.
A total of 305 patients were randomized to receive either 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 IV cisplatin on the 8th day of treatment, followed by the 14-day rest period. The dose of S-1 was the same for both patient groups, 40 mg/m2 twice daily.
The primary endpoint of the SPIRITS study was overall survival. Secondary endpoints included response rate, time to treatment failure, and toxicity. The trial was designed to have 90% power to detect an improvement in median overall survival from 8 to 12 months.
S-1 is a novel oral fluoropyrimidine that combines three pharmacologic agents: Tegafur, which is a prodrug of fluorouracil; gimeracil (5-chloro-2,4-dihydropyridine, CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD) enzyme; and oteracil (potassium oxonate, Oxo), a gastrointestinal side-effects corrector.
S-1 is currently marketed in Japan for the treatment of gastric, colorectal, head and neck, non-small-cell lung, metastatic breast, and pancreatic cancers. In the United States and Europe, the product is in phase III clinical development.