A randomized phase III trial of adjuvant chemotherapy with UFT for completely resected pathological stage I (T1N0M0, T2N0M0) adenocarcinoma of the lung.

Category: Non-Small-Cell Lung Cancer

Authors: H. Kato, M. Tsuboi, M. Ohta, E. Hata, N. Tsubota, N. Hamajima, H. Wada, K. Suemasu, M. Ohta, for the Lung Cancer Research Group; Tokyo Medical University, Tokyo, Japan; the Japan Lung Cancer Research Group, Tokyo, Japan

Abstract:
Background: The oral antimetabolite UFT (a drug composed of tegafur and uracil mixed at the ratio of 1:4) has been shown to be an effective therapy for the treatment of postoperative adjuvant chemotherapy against earlier stages of non-small cell lung cancer in a previous multiinstitutional trial (JCO 14: 1048, 1996).

Objective: To evaluate whether postsurgical adjuvant chemotherapy with oral UFT provides better survival than surgery alone in patients with pathological stage I adenocarcinoma of the lung.

Patients and Methods: Patients with completely resected pathological stage I (T1N0M0, T2N0M0) adenocarcinoma of the lung were randomized with stratification of pathological T stage, gender and age to receive either UFT (250 mg/m²/day) for 2 years oral administration or no chemotherapy (control).

Results: Between January 1994 and March 1997, a total of 999 patients were enrolled, 20 patients were ineligible; of the eligible patients, 491 were assigned to chemotherapy with UFT and 488 to control. Main patient characteristics were as follows; men=48.7%, more than 65 years old=43.9%, pathological T1=73.1%. Overall, 14 (2.9%) UFT patients experienced grade 3 toxicity. Currently, at a median follow up of 70 months, 979 patients are available for survival analysis, 154 patients have died (65 in the UFT group, 89 in the control group). A statistically significant difference in overall survival was observed between the UFT group and the control group. (p=0.036, by stratified log-rank test). The five year survival rate (5YS) was 87.9% in the UFT group, and 85.4% in the control group, respectively. On subgroup analysis, although there was no survival difference between the two groups among patients with T1 disease (p=0.867), patients with T2 disease had significantly better survival in the UFT group (5YS=84.9%) than in the control group (73.5%) (p=0.005).

Conclusion: This study suggests that the oral administration of UFT (250mg/m²/day) in a postoperative adjuvant setting yields a significant improvement on survival in patients with pathological stage I adenocarcinoma of the lung, especially in stage IB (T2N0M0).