PMID- 25740691
OWN - NLM
STAT- MEDLINE
DCOM- 20150807
LR  - 20181202
IS  - 1432-0843 (Electronic)
IS  - 0344-5704 (Linking)
VI  - 75
IP  - 5
DP  - 2015 May
TI  - First-in-human, phase I/IIa dose-escalation and safety study of balugrastim in 
      breast cancer patients receiving myelosuppressive chemotherapy.
PG  - 929-39
LID - 10.1007/s00280-015-2703-1 [doi]
AB  - PURPOSE: To evaluate safety of balugrastim, a recombinant human serum albumin and 
      granulocyte colony-stimulating factor (G-CSF), administered over a range of 
      therapeutic doses in women with breast cancer receiving doxorubicin plus 
      docetaxel chemotherapy. METHODS: The phase I, sequential dose-escalation first 
      segment compared subcutaneous balugrastim 50, 150, 300, and 450 microg/kg during 
      chemotherapy cycles 0-2. The randomized (2:2:1), open-label, phase IIa second 
      segment compared balugrastim 300 or 450 microg/kg with pegfilgrastim 6 mg during 
      chemotherapy cycles 1 and 2. RESULTS: In the phase I segment, balugrastim was 
      escalated to 450 microg/kg in 13 patients without dose-limiting toxicity. Three 
      (9.7 %) of the 31 adverse events (AEs) reported in nine patients were grade 3 
      (agranulocytosis, vomiting, hypertension); none was grade 4. In the open-label 
      phase IIa segment (N = 51), the majority of the 64 AEs reported in 31 (75.6 %) 
      balugrastim-treated patients were grade 1 (59.4 %), with 39.1 % grade 2, 1.6 % 
      grade 3 (one AE of vomiting), and none grade 4. Of the 16 AEs reported in seven 
      (70.0 %) pegfilgrastim-treated patients, 87.5 % were grade 1, 6.3 % were grade 2, 
      6.3 % were grade 3 (one AE of thrombocytopenia), and none were grade 4. Overall, 
      there were six bone pain AEs reported, one in the balugrastim 300 microg/kg group and 
      five in the balugrastim 450 microg/kg group. No AEs in either study necessitated 
      treatment interruption/discontinuation. The incidence and duration of grade 3-4 
      neutropenia were similar between balugrastim- and pegfilgrastim-treated patients. 
      CONCLUSIONS: Balugrastim was well tolerated in this small population of breast 
      cancer patients.
FAU - Avisar, Noa
AU  - Avisar N
AD  - Teva Pharmaceuticals, Netanya, Israel.
FAU - Adar, Liat
AU  - Adar L
FAU - Bock, Jason
AU  - Bock J
FAU - Muller, Udo
AU  - Muller U
FAU - Shen, David
AU  - Shen D
FAU - Barash, Steve
AU  - Barash S
FAU - Pukac, Laurie
AU  - Pukac L
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20150305
PL  - Germany
TA  - Cancer Chemother Pharmacol
JT  - Cancer chemotherapy and pharmacology
JID - 7806519
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Serum Albumin)
RN  - 0 (Taxoids)
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
RN  - 15H5577CQD (Docetaxel)
RN  - 3A58010674 (pegfilgrastim)
RN  - 3WJQ0SDW1A (Polyethylene Glycols)
RN  - 80168379AG (Doxorubicin)
RN  - PVI5M0M1GW (Filgrastim)
RN  - T6K4P3HIU8 (balugrastim)
RN  - ZIF514RVZR (Serum Albumin, Human)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Breast Neoplasms/*drug therapy/metabolism
MH  - Docetaxel
MH  - Dose-Response Relationship, Drug
MH  - Doxorubicin/administration & dosage/adverse effects/pharmacokinetics
MH  - Female
MH  - Filgrastim
MH  - Granulocyte Colony-Stimulating Factor/adverse 
      effects/pharmacokinetics/*therapeutic use
MH  - Humans
MH  - Middle Aged
MH  - Polyethylene Glycols
MH  - Recombinant Fusion Proteins/adverse effects/pharmacokinetics/*therapeutic use
MH  - Recombinant Proteins/adverse effects/pharmacokinetics/therapeutic use
MH  - Serum Albumin/adverse effects/pharmacokinetics/*therapeutic use
MH  - Serum Albumin, Human
MH  - Taxoids/administration & dosage/adverse effects/pharmacokinetics
EDAT- 2015/03/06 06:00
MHDA- 2015/08/08 06:00
CRDT- 2015/03/06 06:00
PHST- 2014/08/28 00:00 [received]
PHST- 2015/02/11 00:00 [accepted]
PHST- 2015/03/06 06:00 [entrez]
PHST- 2015/03/06 06:00 [pubmed]
PHST- 2015/08/08 06:00 [medline]
AID - 10.1007/s00280-015-2703-1 [doi]
PST - ppublish
SO  - Cancer Chemother Pharmacol. 2015 May;75(5):929-39. doi: 
      10.1007/s00280-015-2703-1. Epub 2015 Mar 5.