Phase Ii Trial Of Sequential Dose-Dense Epirubicin/Cyclophosphamide (E/C) Followed By Docetaxel/Capecitabine (D/X) As Adjuvant Or Neoadjuvant Chemotherapy For Patients With Her2-Negative Breast Cancer (Bc)

635 Background: Recent improvements in adjuvant chemotherapy for HER2- BC include: 1) dose density and 2) concurrent or sequential anthracycline/taxane regimens. Further, the addition of capecitabine to docetaxel (D/X) may prove valuable in this setting, based on its superiority over docetaxel alone in metastatic breast cancer (MBC), which is possibly explained by docetaxel-induced upregulation of thymidine phosphorylase (TP), the target of capecitabine. In addition, immediate prior use of E/C also upregulates tumor TP. We report the results of dose-dense E/C followed by D/X in patients with HER2-negative nonmetastatic BC. Methods: Pts with HER2-, either node-positive (N+) or locally advanced breast cancer (LABC), and normal end-organ function were eligible. Treatment included 4 cycles of dose-dense E/C (100/600 mg/m2) + G-CSF Q2 weeks, followed by 4 cycles of docetaxel (75 mg/m2)/capecitabine (1,000 mg/m2 Q12 hours x 14 days) Q3 weeks. LABC pts were treated preoperatively. Subsequently, all pts received radiotherapy, and hormone treatment if estrogen (ER) or progesterone receptor (PR) +. Results: 55 pts were enrolled: 35 N+ (median 2 nodes involved, range 1–13), 20 LABC. Median age was 50 (27–73). ER and PR were present in 80% and 72% of tumors, respectively. Five pts developed grade (G) 3 neutropenic fever (4 after E/C, 1 after D/X). Hand-foot syndrome (HFS) was prominent (45% G3) in the first 20 pts (1,000 mg/m2 of capecitabine). The dose of capecitabine was subsequently reduced to 800 mg/m2. At this dose, the next 35 pts had only 14% G3 HFS. No G4–5 toxicities were observed. All 20 patients treated preoperatively responded clinically, with 10 CRs. Six patients (30%) experienced a pathological CR, and 3 additional patients had pT0N1 tumors. At median follow-up of 2 (1–2) years only 2 pts have relapsed, with event-free and overall survival rates of 96% and 98%, respectively. Conclusions: Sequential dose-dense E/C followed by D/X (requiring a lower capecitabine dose than that approved for MBC) has favorable toxicity and activity profiles for the adjuvant or neoadjuvant treatment of HER2- BC. These early encouraging results warrant further testing of this combination. No significant financial relationships to disclose.