Uracil-tegafur (often referred to as UFT) is an oral chemotherapeutic agent combining tegafur, a prodrug that is converted to fluorouracil in the liver, and uracil, which enhances serum levels of fluorouracil by inhibiting its enzymatic degradation. Previous phase-three trials of UFT for non–small-cell lung cancer showed that its benefits were most apparent in patients with stage I adenocarcinomas (i.e., only local tumor metastasis, no nodal involvement). Kato and colleagues reported on survival data from a trial of UFT use in patients with stage I adenocarcinomas of the lung.
Eligible participants had undergone complete surgical resection of their lung cancer. Exclusion criteria included preoperative anticancer treatment, severe postoperative complications (e.g., pneumonia, empyema), and marked laboratory abnormalities (e.g., very low white blood cell count or platelet count, anemia). Of the 999 patients initially enrolled, 20 were excluded from data analysis. Trial participants were randomized within 28 days of surgical resection to a two-year course of UFT (250 mg per m2 of body surface area per day) given in twice-daily oral doses, or placebo. The UFT doses were reduced to 200 mg per m2 in patients with moderate (grade 2) adverse reactions; therapy was stopped if any severe (grade 3) toxicity occurred. The average age at enrollment was 62 years, and 51 percent of patients were women.
At five years after surgery, the overall survival rate for patients assigned to UFT was 88 percent compared with 85 percent of patients who received placebo; this difference was statistically significant. Subgroup analysis revealed that the survival advantage was limited to patients with T2 disease (i.e., tumors larger than 3 cm in diameter or with spread to the visceral pleural surface). Patients with T1 disease (i.e., smaller tumors, no pleural spread) derived no significant benefit from UFT therapy. Grade 3 adverse reactions such as anorexia, nausea, vomiting, diarrhea, and elevated liver transaminase levels occurred in 2 percent of patients who received UFT.
The authors conclude that two years of postoperative oral chemotherapy with UFT in patients with stage I T2 adenocarcinoma of the lung provides a small but statistically significant survival advantage. In an accompanying editorial, Diasio asks whether the standard of care for stage I lung cancer should be changed to include postoperative chemotherapy, given the positive results of this trial.