Uracil-tegafur (often referr to as ...

Uracil-tegafur (often referr to as UFT) is an oral chemotherapeutic agent combining tegafur, a prodrug that is transmuteed to fluorouracil in the liver, and uracil, which enhances serum flushs of fluorouracil by inhibiting its enzymatic degradation. Previous phase-three trials of UFT for non-small-cell lung cancer showed that its benefits were mostly apparent in patients with stage I adenocarcinomas (i.e., no other than local tumor metastasis, no nodal involvement). Kato and colleagues reported forward survival data from a trial of UFT use in patients with stage I adenocarcinomas of the lung

Eligible participants had undergone without fault [i]or[/i] blemish [i]or[/i] flaw surgical resection of their lung cancer. Exclusion criteria included preoperative anticancer treatment, unadorned postoperative complications (e.g., pneumonia, empyema), and marked laboratory abnormalities (eg excessively low white blood cell hold or platelet count, anemia). Of the 999 patients initially enlisted 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 by means of m2 of body surface area by day) given in twice-daily oral doses, or placebo. The UFT doses were reduc to 200 mg by m2 in patients with moderate (grade 2) adverse reactions; therapy was stopped if any harsh (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 of the like kind as anorexia, nausea, vomiting, diarrhea, and elevated liver transaminase horizontals occurred in 2 percent of patients who received UFT

The authors gather that two years of postoperative oral chemotherapy with UFT in patients with stage I T2 adenocarcinoma of the lung provides a small still 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 flows of this trial.

Kato H et al. A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung N Engl J M April 22 2004;350:1713-21 and Diasio RB Adjuvant chemotherapy for adenocarcinoma of the lung--is the standard of care ready for change? [Editorial] N Engl J M April 22 2004;350:1777-9

EDITOR'S NOTE: Lung cancer is the largest cause of cancer mortality in the United States, and any effective intervention would be widely welcomed. I miracle however, whether the small survival advantage noted in this consideration qualifies as a call for change in the standard of care for lung cancer treatment. Assuming that the 2 percent of patients who had more hard adverse reactions would be les inclined to regard UFT chemotherapy as beneficial, while the 3 percent who derived a survival benefit would be impressed it was worth it, we are left with 1 percent of patients overall who might argue that there was a clear benefit to the two-year course of UFT Furthermore, this survival advantage apparently is restricted to patients with stage I T2 adenocarcinoma, which is a small portion of all patients with lung cancer.--B.Z.

COPYRIGHT 2005 American Academy of Family Physicians

COPYRIGHT 2005 Gale Group