S-1 combined with docetaxel following doxorubicin plus cyclophosphamide as neoadjuvant therapy in breast cancer: Phase II trial

Background: This study evaluated the efficacy and safety of S-1 combined with docetaxel (SD) following doxorubicin plus cyclophosphamide (AC) as neoadjuvant therapy in patients with HER2-negative, stage II-III breast cancer. Methods: Patients received AC every 3 weeks for four cycles followed by S-1 (30 mg/m² orally b.i.d. on days 1-14) and docetaxel (75 mg/m² i.v. on day 1) every 3 weeks for four cycles. The primary endpoint was the pathological complete response (pCR) rate in breast and axillary lymph nodes. Results: The study included 49 patients with a median age of 43 years. The median breast tumor size was 4.0 cm by palpation. All patients were positive for involvement of axillary lymph node and five patients also had supraclavicular lymph node metastasis, which was confirmed by histological examination. In total, 85.4% of patients (41/49) completed eight cycles of therapy and 95.9% of patients (47/49) received curative surgery. The pCR rate was 22.5% (n = 11). The clinical response rate was 67.4%. During SD chemotherapy, the most frequent grade 3-4 toxicity was neutropenia (8.5% by cycle). There was a single treatment-related mortality from severe neutropenia. Grade 3 S-1 specific toxicities such as epigastric pain (12.2% by person), stomatitis (4.1% by person), and diarrhea (2.0% by person) were also observed. In particular, gastrointestinal discomfort led to dose reduction of S-1 in 45.8% of patients.Conclusions: Given all axillary lymph node positive diseases, neoadjuvant S-1 combined with docetaxel following AC showed a favorable anti-tumor activity but gastrointestinal discomfort should be carefully considered for future studies. Trial registration: NCT00994968.