P3-14-24: A Phase II Trial of TS-1 and Docetaxel Followed by 5-FU/Epirubicin/Cyclophosphamide (FEC) as Preoperative Treatment in Women with Stage II/III Breast Cancer.

Abstract

Abstract Background: TS-1 is an oral anticancer drug, composed of tegafur, gimestat and otastat potassium in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-Fuorouracil. In vivo xenograft model showed a synergistic effect of combination chemotherapy with TS-1 and docetaxel through down-regulation of dihydropyrimidine dehydrogenase (DPD). (Suto et al, Oncology Reports 2006) The sequential combination of anthracycline and taxane is a standard of care in the preoperative setting, as well as the adjuvant setting. This study's purpose was to determine the efficacy of TS-1 and docetaxel followed by fluorouracil/epirubicin/cyclophosphamide (FEC) in the preoperative setting. Patients and Methods: Patients with stage II/III breast cancer received 4 cycles of TS-1 (TS-1 80 mg/m2 on days 1–14 and docetaxel 40 mg/m2 on day 1 every 3 weeks), followed by 4 cycles of FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2 on day 1 every 3 weeks). The tumor objective response was assessed by both caliper and ultrasound. Primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints were the clinical response rate, adverse drug reactions, and the breast conservation rate. Results: From November 2009 to December 2010, 39 patients were enrolled and 38 patients were assessable for clinical and pathologic responses. The overall response rate (caliper) was 81.5% and ultrasound response rate was 76.3%. The pCR rate was 13.2% (5/38). The breast-conserving rate in patients whose tumor size was 3 cm or smaller was 92.9%, and 54.5% of patients whose tumor size was larger than 3 cm underwent breast-conserving surgery. The ratio of Ki-67 positive cell and progesterone receptor (PgR) status were significantly correlated with pCR. Grade 4 neutropenia was observed in a patient (2.6%) at the first cycle. The most common grade 3/4 non-hematologic adverse event was hand-foot syndrome, observed in 3 patients (7.9%). One patient (2.6%) showed grade 3 diarrhea. Conclusions: These results indicate that the sequential combination of TS-1 and docetaxel followed by FEC is a well-tolerated, effective neoadjuvant treatment for stage II/III breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-24.