A phase II trial of dose-dense neoadjuvant gemcitabine, epirubicin, and albumin-bound paclitaxel with pegfilgrastim in the treatment of patients with locally advanced breast cancer.
BACKGROUND
Neoadjuvant anthracycline/taxane combinations, with or without gemcitabine, produce pathologic complete responses (pCRs) in 15%-25% of patients. In this multicenter phase II study, we attempted to increase efficacy and decrease toxicity of a 3-drug gemcitabine-containing neoadjuvant regimen by administering dose-dense therapy with pegfilgrastim, and including albumin-bound paclitaxel as the taxane.


METHODS
A total of 123 patients with locally advanced breast cancer were enrolled. Patients were treated with 6 doses of neoadjuvant gemcitabine 2000 mg/m2, epirubicin 50 mg/m2, and albumin-bound paclitaxel 175 mg/m2 intravenously administered at 14-day intervals. Following neoadjuvant chemotherapy, patients underwent either mastectomy or breast conservation surgery; pathologic response to treatment was assessed. Postoperatively, patients received 4 doses of gemcitabine 2000 mg/m2 with albumin-bound paclitaxel 220 mg/m2 at 14-day intervals. Pegfilgrastim 6 mg was administered subcutaneously on day 2 following each dose of chemotherapy.


RESULTS
A total of 116 patients (95%) completed neoadjuvant chemotherapy and had subsequent surgical resection. Twenty-three patients (20%) had a pCR. The estimated 3-year progression-free survival (PFS) and overall survival rates were 48% and 86%, respectively. Neoadjuvant treatment was well tolerated; only 11% of the patients had grade 3/4 neutropenia, with 1 episode of neutropenic fever. Other grade 3/4 toxicities occurred in < 10% of the patients.


CONCLUSIONS
Neoadjuvant biweekly chemotherapy with gemcitabine/epirubicin/albumin-bound paclitaxel with pegfilgrastim is feasible and well tolerated. The pCR rate of 20% and the 3-year PFS rate of 48% are similar to results achieved with other commonly used neoadjuvant regimens.
Yardley
Denise A
DA
Sarah Cannon Research Institute, Nashville, TN 37203, USA.
Zubkus
John
J
Daniel
Brooke
B
Inhorn
Roger
R
Lane
Cassie M
CM
Vazquez
Elizabeth R
ER
Naot
Yuval
Y
Burris
Howard A
HA
Hainsworth
John D
JD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D000093542:Gemcitabine
D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D011994:Recombinant Proteins; D003841:Deoxycytidine; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D015251:Epirubicin; D017239:Paclitaxel; D000069585:Filgrastim; D000093542:Gemcitabine