UFT and S-1 for treatment of primary lung cancer.
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.
Tanaka
Fumihiro
F
Department of Thoracic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya 660-8501, Japan. ftanaka@hyo-med.ac.jp
Wada
Hiromi
H
Fukushima
Masakazu
M
D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000037:antagonists & inhibitors; D004338:Drug Combinations; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D019317:Evidence-Based Medicine; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality / Q000473:pathology; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018714:Radiotherapy, Adjuvant; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D004338:Drug Combinations; D004791:Enzyme Inhibitors; C096910:UFT(R) drug; C079198:S 1 (combination); D005641:Tegafur; D014498:Uracil; D010094:Oxonic Acid; D042943:Dihydrouracil Dehydrogenase (NADP)