A phase II neoadjuvant trial of sequential nanoparticle albumin-bound paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide in locally advanced breast cancer.
BACKGROUND
Neoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer (LABC). Various regimens have explored the addition of newer agents to determine safety and efficacy. The aim of this phase II study was to incorporate albumin-bound paclitaxel with sequential anthracycline-based therapy.


METHODS
Sixty-six women with LABC but without prior treatment and regardless of hormone receptor or HER2 status were enrolled. All patients were to receive albumin-bound paclitaxel weekly for 12 weeks followed by 5-fluorouracil/ epirubicin/cyclophosphamide (FEC) every 3 weeks for 4 cycles. Trastuzumab was allowed in HER2-positive (HER2+) patients. Primary endpoint was pathologic complete response (pCR; CR) in breast. Secondary endpoints included pCR in breast and nodes, clinical CR, 2-year progression-free survival, and overall survival.


RESULTS
Sixty-five patients received at least 1 dose of chemotherapy and were included in this analysis. Sixty-three patients completed 4 cycles of albumin-bound paclitaxel. Sixty-two patients received at least 1 dose of FEC, and 58 completed 4 cycles. Seventeen of 19 HER2+ women received trastuzumab. The pCR in breast was 29% (19 of 65). For the HER2+ subset, the pCR was 58% (11 of 19). Both albumin-bound paclitaxel and FEC were well tolerated. The most significant toxicities were grade 2/3 neuropathy (16%) with albumin-bound paclitaxel and grade 3/4 febrile neutropenia (7%) with FEC.


CONCLUSIONS
Albumin-bound paclitaxel given over 12 weeks is well tolerated. Albumin-bound paclitaxel should be further evaluated in a randomized setting in both adjuvant and neoadjuvant trials.
National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh, PA Centre Hospitalier, de l'Université de Montreal (CHUM), Montreal, Quebec, Canada.
André
A
Robidoux
Aman U
AU
Buzdar
Emmanuel
E
Quinaux
Samuel
S
Jacobs
Priya
P
Rastogi
Virginie
V
Fourchotte
Rami J
RJ
Younan
Eduardo R
ER
Pajon
Ibrahim A
IA
Shalaby
Ajit M
AM
Desai
Louis
L
Fehrenbacher
Charles E
CE
Geyer
Eleftherios P
EP
Mamounas
Norman
N
Wolmark
D000328:Adult; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D053758:Nanoparticles / Q000008:administration & dosage / Q000009:adverse effects; D020360:Neoadjuvant Therapy / Q000379:methods*; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D015251:Epirubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D005472:Fluorouracil