Randomized phase II clinical trial of comparison of epirubicin (E) plus cyclophosphamide (C) and weekly paclitaxel (P) as primary systemic therapy (PST) in patients (pts) with stages II and III breast cancer (BC)

Abstract

568 Background: Response and survival rates achieved by anthracycline and P (q 3 weeks [W]) pts with metastatic BC are comparable (ECOG1193). Weekly P is expected to produce higher response rates and lower hematologic toxicity than tri-weekly P for PST (MDACC2002). This study evaluated the activity and toxicity of weekly P therapy compared with EC therapy for stage II and III BC treated by PST. The primary endpoint was the pathologic complete response(pCR) rate. Methods: Pts with histologically confirmed BC, stage II or III, performance status 0–2, and absence of prior chemotherapy were randomized to either Arm A (EC: E 75mg/m2 and C 600 mg/m2 every 3 W for 4 cycles) or Arm B (weekly P: P 80 mg/m2 weekly for 12 W). Pts received PST for 12 W, then underwent surgery. All pts received a cross-over regimen as adjuvant chemotherapy after surgery. Results: Between November 2003 and May 2006, 171 pts were recruited. One hundred fifty-six pts (Arm A: n=80, Arm B: n=76) were evaluable. The clinicopathologic characteristics of pts (age, tumor size, stage, nodal status, hormone receptor and HER2 status) were well balanced in the two arms. Pathologic effect on the primary lesion in 156 pts showed that the pCR rates were 12.5% in Arm A and 18.5% in Arm B (p=0.22). Clinical overall response (OR) rate was 65.0% in Arm A and 64.5% in Arm B. Disease-free survival rate of 43 month was 83.6% in Arm A and 81.4% in Arm B (p=0.96). OR rate in HER2-positive pts (67.7% vs. 65.6%) and the breast conservation rate (50% vs. 55.3%) were equal in both arms. The incidence of grade 3/4 neutropenia (26.3% vs. 5.3%, p=0.0004) was lower in the Arm B than in Arm A, while that of vomiting (18.8% vs. 5.3%, p=0.01) was higher in Arm A. Nausea and mucositis were more frequently seen in Arm A than in Arm B, but there was no significant difference. The incidence of neuropathy (3.8% vs. 39.5%, p<0.001) was higher in Arm B. Conclusions: OR rate and pCR rate were equal in both arms. Weekly P was associated with less toxicity than EC therapy, but more frequently induced neuropathy. Therefore, induction of PST by weekly P therapy seems to be promising. No significant financial relationships to disclose.