title: A Phase III Study of Balugrastim Versus Pegfilgrastim in Breast Cancer Patients Receiving Chemotherapy With Doxorubicin and Docetaxel.
abstract: OBJECTIVE
  This study aimed to evaluate the efficacy and safety of once-per-cycle balugrastim versus pegfilgrastim for neutrophil support in breast cancer patients receiving myelosuppressive chemotherapy.
  
  
  METHODS
  Breast cancer patients (n = 256) were randomized to 40 or 50 mg of subcutaneous balugrastim or 6 mg of pegfilgrastim ≈24 hours after chemotherapy (60 mg/m(2) doxorubicin and 75 mg/m(2) docetaxel, every 21 days for up to 4 cycles). The primary efficacy parameter was the duration of severe neutropenia (DSN) in cycle 1. Secondary parameters included DSN (cycles 2-4), absolute neutrophil count (ANC) nadir, febrile neutropenia rates, and time to ANC recovery (cycles 1-4). Safety, pharmacokinetics, and immunogenicity were assessed.
  
  
  RESULTS
  Mean cycle 1 DSN was 1.0 day with 40 mg of balugrastim, 1.3 with 50 mg of balugrastim, and 1.2 with pegfilgrastim (upper limit of 95% confidence intervals for between-group DSN differences was <1.0 day for both balugrastim doses versus pegfilgrastim). Between-group efficacy parameters were comparable except for time to ANC recovery in cycle 1 (40 mg of balugrastim, 2.0 days; 50 mg of balugrastim, 2.1; pegfilgrastim, 2.6). Median terminal elimination half-life was ≈37 hours for 40 mg of balugrastim, ≈36 for 50 mg of balugrastim, and ≈45 for pegfilgrastim. Antibody response to balugrastim was low and transient, with no neutralizing effect.
  
  
  CONCLUSIONS
  Once-per-cycle balugrastim is not inferior to pegfilgrastim in reducing cycle 1 DSN in breast cancer patients receiving chemotherapy; both drugs have comparable safety profiles.
  
  
  CONCLUSIONS
  This paper provides efficacy and safety data for a new, once-per-cycle granulocyte colony-stimulating factor, balugrastim, for the prevention of chemotherapy-induced neutropenia in patients with breast cancer receiving myelosuppressive chemotherapy. In this phase III trial, balugrastim was shown to be not inferior to pegfilgrastim in the duration of severe neutropenia in cycle 1 of doxorubicin/docetaxel chemotherapy, and the safety profiles of the two agents were similar. Once-per-cycle balugrastim is a safe and effective alternative to pegfilgrastim for hematopoietic support in patients with breast cancer receiving myelosuppressive chemotherapy associated with a greater than 20% risk of developing febrile neutropenia.
authors.affiliation: Chelyabinsk Regional Clinical Oncology Dispensary, Chelyabinsk, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Gladkov
authors.affiliation: N.N. Petrov Research Institute of Oncology, St. Petersburg, Russia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Moiseyenko
authors.affiliation: Dnipropetrovsk Medical Academy, City Clinical Hospital, Dnipropetrovsk, Ukraine.
authors.forename: Igor N
authors.initials: IN
authors.lastname: Bondarenko
authors.affiliation: Lviv Cancer Center, Lviv, Ukraine.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Shparyk
authors.affiliation: Teva Biopharmaceuticals, Rockville, Maryland, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Barash
authors.affiliation: Teva Pharmaceuticals, Inc., Netanya, Israel.
authors.forename: Liat
authors.initials: L
authors.lastname: Adar
authors.affiliation: Teva Pharmaceuticals, Inc., Netanya, Israel noa.avisar@teva.co.il.
authors.forename: Noa
authors.initials: N
authors.lastname: Avisar
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001772:Blood Cell Count; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy / Q000473:pathology; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D011092:Polyethylene Glycols; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects; D012709:Serum Albumin / Q000008:administration & dosage* / Q000009:adverse effects; D000075462:Serum Albumin, Human; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012709:Serum Albumin; D043823:Taxoids; D016179:Granulocyte Colony-Stimulating Factor; D000077143:Docetaxel; C455861:pegfilgrastim; D011092:Polyethylene Glycols; D004317:Doxorubicin; D000069585:Filgrastim; C000600093:balugrastim; D000075462:Serum Albumin, Human
keywords: Balugrastim; Breast cancer; Granulocyte colony-stimulating factor; Myelosuppressive therapy; Pegfilgrastim