Teysuno launched for advanced gastric cancer

PHARMACOLOGY

Teysuno is an oral fluoropyrimidine antineoplastic agent. It is a fixed dose combination of three active substances: tegafur, which after absorption is converted into 5-fluorouracil (5-FU); gimeracil, a dihydropyrimidine dehydrogenase (DPD) inhibitor that prevents degradation of 5-FU by the body; and oteracil, an orotate phosphoribosyltransferase (OPRT) inhibitor that decreases the activity of 5-FU in normal gastrointestinal mucosa. This combination maintains 5-FU exposure to sustain anti-tumour activity while reducing toxicity associated with 5-FU alone.¹

CLINICAL STUDIES

The FLAGS Trial conducted in 24 countries randomised 1,053 patients to receive intravenous cisplatin plus either 5-FU by intravenous infusion or the fixed-dose combination of tegafur, gimeracil and oteracil (molar ratio 1.0:0.4:1.0) by mouth. Patients received 5-FU at 1g/m²/24 hours for 120 hours and cisplatin 100mg/m² on day 1, repeated every 28 days (n=526) or the fixed-dose combination at 50mg/m² daily (expressed as tegafur dose) in 2 divided doses for 21 days and cisplatin at 75mg/m² on day 1, repeated every 28 days (n=527).²

The primary endpoint was superiority in overall survival from cisplatin plus combination therapy and cisplatin plus 5-FU in patients with advanced, untreated gastric or gastroesophageal adenocarcinoma. The secondary endpoints were response rate, progression-free survival, time to treatment failure and safety.²

Median overall survival was 8.6 months in the cisplatin/fixed-dose combination group and 7.9 months in the cisplatin/5-FU group (HR 0.92; 95% CI 0.80 to 1.05; p=0.20).²

Whilst the cisplatin/fixed-dose combination did not prolong the overall survival of patients with advanced gastric or gastroesophageal adenocarcinoma compared with cisplatin/5-FU, it did have a significantly improved safety profile.

The incidence of grade 3/4 neutropenia was reduced in the cisplatin/fixed-dose combination group compared with the cisplatin/5-FU group (32.3% versus 63.6%; p<0.01), as was the incidence of complicated neutropenia (5.0% versus 14.4%; p≤0.01).²

References:

1. Teysuno Summary of Product Characteristics, March 2011.
2. Ajani JA et al. J Clin Oncol 2010; 28: 1547-53.

View Teysuno drug record

Further information: Nordic Pharma Ltd