Abstract P1-13-10: Efficacy, toxicity and quality of life in older patients with early-stage breast cancer treated with oral Tegafur-uracil or classical CMF (cyclophosphamide, methotrexate, and fluorouracil): an exploratory analysis of National Surgical Adjuvant Study for Breast Cancer (N-SAS BC) 01 Trial
Authors: Hara F , Watanabe T , Shimozuma K , Ohashi Y 
Published: August 2014

Abstract
Background: It is critically important to consider the issue of treatment for older breast cancer patients in developed countries where aging has been rapidly advanced such as in Japan. According to Oxford Overview analysis of 15-year results, benefit of adjuvant chemotherapy in older than 70 years remains uncertain. Recently CALGB 49907 trial clearly showed standard chemotherapy of either cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin plus cyclophosphamide (AC) is superior to capecitabine in patients with early-stage breast cancer who are 65 years or older. In contrast, we demonstrated equivalent efficacy between six cycles of classical CMF and 2 years of oral Tegafur-uracil (UFT) in phaseIII randomized controlled trial: N-SAS BC01 (Watanabe T et al, JCO 2009). Of interest, UFT showed a trend toward better suppression of recurrence in patients over 50 years of age in this trial. In current exploratory analysis, we sought to examine whether UFT is not inferior to CMF in terms of efficacy, toxicity and quality of life (QOL) in older patients with early-stage breast cancer.
Patients and Methods: N-SAS BC 01 trial was a randomly assigned trial comparing adjuvant oral UFT with classical CMF in patients with node negative, high risk breast cancer. In this exploratory analysis, patients of 65 years or older enrolled in N-SAS BC 01 trial were analyzed in terms of efficacy, toxicity and quality of life.
Results: Of the 707 patients enrolled in N-SAS BC 01 trial, 97 patients (13.7%) were 65 years or older. Median age was 68 years (range, 65 to 75 years). The 5-year relapse-free survival (RFS) rate was 92.5% in the CMF arm and 93.0% in the UFT arm. Overall survival (OS) rate at 5 years were 98.1% and 97.7%, respectively. The hazard ratios of the UFT arm relative to the CMF arm were 1.07 for RFS (95% CI, 0.31 to 3.55) and for OS (95% CI, 0.15 to 10.25). However 95 % CIs were very wide due to the small sample size. Among patients who received CMF, frequency of grade 3/4 leukopenia (3.8%) and neutropenia (13.5%) were higher than 0% and 4.8% with UFT, respectively. Similarly, grade 3/4 increased liver enzyme and nausea/vomiting were more frequent with CMF than with UFT. In contrast, elevation of total bilirubin and diarrhea were more observed in UFT arm. Compared with patients received CMF, patients with UFT had better QOL scores assessed by EORTC QLQ-C30/BR23 and the FACT-B questionnaire. The rate of adherence was 79.2% (42/53) at 6 months in the CMF arm and 74.4% (32/43) at 2 years in the UFT arm.
Conclusion: The result of this study indicated that UFT might not be inferior to CMF in patient with early stage breast cancer who are 65 years of age or older in terms of efficacy, toxicity and QOL. UFT would be a promising option for adjuvant chemotherapy in older women with node-negative, high-risk breast cancer. Further larger randomized clinical trial in this patient population would be warranted to validate these results.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-10.