Neoadjuvant dose-dense (DD) concurrent doxorubicin (A) and docetaxel (T) for stage III breast cancer (BC)
10721 Background: The addition of taxanes to anthracycline therapy results in improved disease-free survival (DFS) in the adjuvant setting, and increased pathologic complete response rates (pCR) in the neoadjuvant setting. DD chemotherapy improves DFS and overall survival (OS). We evaluated neoadjuvant DD concurrent AT. Methods: Eligible patients (pts) with stage III BC were treated with AT q 14 days at 1 of 3 dose levels; L1 = 60 mg/m2 for both drugs (4 pts), L2 = A 75 mg/m2 and T 60 mg/m2 (6 pts) or L3 = 75 mg/m2 for both drugs (7 pts) × 6 cycles with G-CSF. Dexrazoxane was given after a cumulative dose of 300 mg/m2 of A. Pts were stratified to post-operative moderate risk (ModR) (≥ partial response, ≤ 3 lymph nodes (LN)) and received adjuvant IV cyclophosphamide (C) 600 mg/m2, methotrexate 40 mg/m2, 5FU 600 mg/m2 IV q 21 d × 6 (CMF), or high risk (HiR) (≤ minor response +/or ≥ 4 LN) and received C 3 gm/m2 q 14 d x 3. Primary endpoints were clinical and pathologic response rates of neoadjuvant AT. Sample size was 42 pts to estimate pCR and provide 90% confidence the true incidence of severe toxicity is <10%. Results: 17 pts with stage III BC were enrolled between 2/1999 and 7/2001; accrual was halted after data on pre-operative trastuzumab were presented. Median age was 50 yrs [range: 34–69]. 3/17 pts (17.6%) had a pCR, and 3 pts had near pCR (residual foci ≤ 1mm), 4/17 (23.5%) had path (-) LN, 7/17 (41%) had a lumpectomy, 7/17 (41%) required dose reductions of AT due to grade 4 neutropenia (5 pts) and grade 3 neuropathy (2 pts). 3 pts required treatment cessation; 1 pt (L2) for prolonged neutropenic fever and 2 pts (L3) for decreased ejection fraction and for acute renal failure. 15 pts were ModR and received adjuvant CMF, 1/2 pts stratified to high dose C declined it and received CMF. Median follow-up is 63 months [range: 28–80] with 13/17 (76.5%) pts surviving, and 12/17 (70.5%) pts surviving and free of disease. Conclusion: Neoadjuvant DD AT every 2 weeks is well-tolerated, with promising activity and survival in locally advanced BC. [Table: see text]