Tegafur + gimeracil + oteracil. Just another fluorouracil precursor

Patients with advanced-stage gastric cancer and inoperable locoregional extension rarely survive more than a few months. Chemotherapy based on intravenous fluorouracil or oral capecitabine slightly prolongs overall survival. An oral fixed-dose combination of tegafur + gimeracil + oteracil (Teysuno degrees, Nordic) has been approved in the European Union for the treatment of advanced gastric cancer. Like capecitabine, tegafur is a metabolic precursor of fluorouracil. It is combined with gimeracil in order to increase its bioavailability and with oteracil to try to reduce its gastrointestinal toxicity. In two randomised, controlled but unblinded trials including 91 and 129 patients with advanced gastric cancer, there was no significant difference in median overall survival times between patients who received the tegafur + gimeracil + oteracil combination and those who received oral capecitabine alone (about 9 and 13 months, respectively). However, the study populations were too small to rule out a noteworthy difference in survival between the 2 treatments. Another randomised, unblinded trial compared tegafur + gimeracil + oteracil versus flurorouracil monotherapy in 1029 patients with gastric cancer, which was often metastastic. However, the dose of concomitantly administered cisplatin was lower in the tegafur group, therefore skewing the results. Median overall survival was about 8 months in both groups, and median progression-free survival was about 5 months. Neither outcome differed significantly between the 2 treatments. Compared to capecitabine, the tegafur + gimeracil + oteracil combination appears to cause fewer cases of severe palmoplantar dysaesthesia but more serious gastrointestinal disorders. Like capecitabine, the tegafur + gimeracil + oteracil combination is administered orally twice daily. In practice, when oral therapy is preferred for a patient with advanced gastric cancer, capecitabine is still the best option because it carries a lower risk of serious gastrointestinal adverse effects.