Efficacy of pegfilgrastim and darbepoetin alfa as hematopoietic support for dose-dense every-2-week adjuvant breast cancer chemotherapy.
OBJECTIVE
Dose-dense, every-2-week adjuvant chemotherapy using doxorubicin/cyclophosphamide (AC; 60/600 mg/m2 every 2 weeks x four cycles) followed by paclitaxel (175 mg/m2 every 2 weeks x four cycles), requiring filgrastim on days 3 through 10 of each cycle has been shown to improve survival compared with every-3-week treatment schedules but is associated with greater risk of RBC transfusion (13%). The role of long-acting hematopoietic growth factors in facilitating every-2-week chemotherapy and minimizing hematologic toxicity has not been established.


METHODS
Women with stage I to III breast cancer received dose-dense AC --> paclitaxel as neoadjuvant or adjuvant chemotherapy. Patients received pegfilgrastim 6 mg subcutaneous (SQ) on day 2 of each cycle. Darbepoetin alfa was initiated at 200 microg SQ every 2 weeks for hemoglobin < or = 12 g/dL, and administered thereafter, according to a preplanned algorithm. The primary end points were to evaluate the percentage of patients with febrile neutropenia and the percentage of patients requiring RBC transfusion.


RESULTS
Among 135 women treated on this single arm study, there were two cases of febrile neutropenia (incidence 1.5%). No patients received RBC transfusion. Darbepoetin alfa therapy was initiated in 92% of patients. The modest leukocytosis seen during paclitaxel cycles was attributable, in part, to corticosteroid premedication. Other toxicity and dose-delivery were similar to dose-dense AC --> paclitaxel in Cancer and Leukemia Group B 9741.


CONCLUSIONS
Pegfilgrastim and darbepoetin alfa are effective and safe in facilitating every-2-week AC --> paclitaxel, minimizing rates of febrile neutropenia and RBC transfusion.
Burstein
Harold J
HJ
Dana-Farber Cancer Institute, Boston, MA 02115, USA. hburstein@partners.org
Parker
Leroy M
LM
Keshaviah
Aparna
A
Doherty
Jennifer
J
Partridge
Ann H
AH
Schapira
Lidia
L
Ryan
Paula D
PD
Younger
Jerry
J
Harris
Lyndsay N
LN
Moy
Beverly
B
Come
Steven E
SE
Schumer
Susan T
ST
Bunnell
Craig A
CA
Haldoupis
Margaret
M
Gelman
Rebecca
R
Winer
Eric P
EP
D000328:Adult; D000368:Aged; D000465:Algorithms; D000740:Anemia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001900:Boston / Q000453:epidemiology; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D000068256:Darbepoetin alfa; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D017707:Erythrocyte Transfusion; D004921:Erythropoietin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use*; D006801:Humans; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000453:epidemiology / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D016896:Treatment Outcome
D011994:Recombinant Proteins; D004921:Erythropoietin; D016179:Granulocyte Colony-Stimulating Factor; D000068256:Darbepoetin alfa; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel; D000069585:Filgrastim