S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer, researchers have concluded.
The investigators presented findings from the phase III SPIRITS (S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer) trial, published early online in Lancet Oncology.
S-1 (TS-1, Taiho Pharmaceuticals, Japan) is an orally active combination of tegafur (a prodrug converted by cells to fluorouracil), gimeracil (an inhibitor of dihydropyrimidine dehydrogenase, which degrades fluorouracil), and oteracil (which inhibits phosphorylation of fluorouracil in the GI tract, reducing GI toxic effects of fluorouracil).
The study involved chemotherapy-naive patients with advanced gastric cancer enrolled in 2002-4 at 38 centres in Japan.
They were randomised to receive either combination treatment with S-1 plus cisplatin, or S-1 alone.
The primary endpoint was overall survival and secondary endpoints were progression-free survival, proportions of responders, and safety.
An intention-to-treat analysis found that:
- Median overall survival was longer in patients on combination treatment.
- Progression-free survival was longer in patients on combination treatment.
- Of 87 patients on combination treatment who had target tumours, one patient had a complete response and 46 patients partial responses.
- Of 106 patients on S-1 alone who had target tumours, one patient had a complete response and 32 partial responses.
- More grade 3 or 4 adverse events were reported in the combination treatment group.
- There were no treatment-related deaths in either group.
The drug is currently used in Japan for treating gastric, colorectal, head and neck, non-small cell lung, metastatic breast and pancreatic cancers, and is in phase III clinical development in other countries.
Sanofi-Aventis is collaborating on and leading clinical development and commercialisation of S-1 in Europe and the USA.