UFT and S-1 for treatment of primary lung cancer

Abstract

UFT and S-1 are oral 5-fluorouracil (5-FU) derivative drugs containing an inhibitor of dihydropyrimidine dehydrogenase (DPD); they are defined as DPD-inhibitory fluoropyrimidine (DIF). Because DPD is the key enzyme of 5-FU degradation, 5-FU is not active in primary lung cancers with high DPD activity, which causes rapid degradation of 5-FU. Thus, theoretically, a DIF can overcome a cancer's resistance to 5-FU through inhibiting the enzyme activity of DPD, with the result that 5-FU may be active in primary lung cancer. In fact, UFT has proved to be effective in a postoperative adjuvant setting for early non-small-cell lung cancer (NSCLC) in several randomized controlled studies (RCTs). S-1, in which a more potent DPD inhibitor is combined, is active in advanced NSCLC regardless of the histological cell subtype, and its clinical efficacy in first-line therapy for unresectable advanced disease as well as in postoperative adjuvant therapy for resected disease is now being examined in a variety of RCTs. In the present review, the mechanism of action of UFT and S-1 as well as clinical evidence regarding their use in the treatment of NSCLC are summarized.