The role of tegafur/uracil in pulmonary malignancy

Tegafur/uracil (UFT) is an oral fluorinated pyrimidine composed of a combination of uracil and tegafur in a 4:1 molar ratio. When given on a continuous basis, it yields a fluorouracil area under the concentration-time curve identical to that achieved with isomolar concentrations of fluorouracil administered by continuous infusion. Its 8.7% response rate in advanced non-small cell lung cancer (NSCLC) is modest, but it has demonstrated synergy with cisplatin in human solid tumour xenografts. In combination with cisplatin in patients with advanced NSCLC, response rates of 29 to 43% were observed with acceptable toxicity. Researchers in Japan have demonstrated the utility of this agent as adjuvant therapy after surgical resection, either alone or in combination with cisplatin and vindesine versus observation; long term survival rates exceed 60%, compared with 49% for the control group. Efforts in the US will assess the role of this agent as non-cross-resistant consolidation therapy after a plateau in response has been obtained with platinum-based therapy in advanced disease. They will also recapitulate the Japanese studies, assessing their utility as adjuvant therapy in NSCLC patients who have undergone resection. Finally, ongoing phase I studies are combining this agent with paclitaxel and other systemic agents.