title: A randomized, multicenter, phase II/III study to determine the optimal dose and to evaluate the efficacy and safety of pegteograstim (GCPGC) on chemotherapy-induced neutropenia compared to pegfilgrastim in breast cancer patients: KCSG PC10-09.
abstract: OBJECTIVE
  Pegylated granulocyte-colony-stimulating factor (G-CSF) is frequently used to prevent febrile neutropenia (FN) in patients undergoing chemotherapy with a high risk of myelosuppression. This phase II/III study was conducted to determine the adequate dose of pegteograstim, a new formulation of pegylated G-CSF, and to evaluate the efficacy and safety of pegteograstim compared to pegfilgrastim.
  
  
  METHODS
  In the phase II part, 60 breast cancer patients who were undergoing DA (docetaxel and doxorubicin) or TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy were randomly selected to receive a single subcutaneous injection of 3.6 or 6.0 mg pegteograstim on day 2 of each chemotherapy cycle. The phase III part was seamlessly started to compare the dose of pegteograstim at selected in phase II with 6.0 mg pegfilgrastim in 117 breast cancer patients. The primary endpoint of both the phase II and III parts was the duration of grade 4 neutropenia in the chemotherapy cycle 1.
  
  
  RESULTS
  The mean duration of grade 4 neutropenia for the 3.6 mg pegteograstim (n = 33) was similar to that for the 6.0 mg pegteograstim (n = 26) (1.97 ± 1.79 days vs. 1.54 ± 0.95 days, p = 0.33). The 6.0 mg pegteograstim was selected to be compared with the 6.0 mg pegfilgrastim in the phase III part. In the phase III part, the primary analysis revealed that the efficacy of pegteograstim (n = 56) was non-inferior to that of pegfilgrastim (n = 59) [duration of grade 4 neutropenia, 1.64 ± 1.18 days vs. 1.80 ± 1.05 days; difference, -0.15 ± 1.11 (p = 0.36, 97.5 % confidence intervals = 0.57 and 0.26)]. The time to the absolute neutrophil count (ANC) recovery of pegteograstim (≥2000/μL) was significantly shorter than that of pegfilgrastim (8.85 ± 1.45 days vs. 9.83 ± 1.20 days, p < 0.0001). Other secondary endpoints showed no significant difference between the two groups. The safety profiles of the two groups did not differ significantly.
  
  
  CONCLUSIONS
  Pegteograstim was shown to be as effective as pegfilgrastim in the reduction of chemotherapy-induced neutropenia in the breast cancer patients who were undergoing chemotherapy with a high risk of myelosuppression.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Chungbuk National University Hospital, CheongJu, South Korea.
authors.forename: Ki Hyeong
authors.initials: KH
authors.lastname: Lee
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Division of Hemato-oncology, Department of Internal Medicine, Inha University Hospital, Incheon, South Korea.
authors.forename: Moon Hee
authors.initials: MH
authors.lastname: Lee
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Chungbuk National University Hospital, CheongJu, South Korea.
authors.forename: Hye Sook
authors.initials: HS
authors.lastname: Han
authors.affiliation: Division of Hemato-oncology, Department of Internal Medicine, Inha University Hospital, Incheon, South Korea.
authors.forename: Joo Han
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, Keimyung University Dongsan Hospital, Daegu, South Korea.
authors.forename: Keon Uk
authors.initials: KU
authors.lastname: Park
authors.affiliation: Center for Breast Cancer, Hospital of the National Cancer Center, National Cancer Center, Goyang, South Korea.
authors.forename: In Hae
authors.initials: IH
authors.lastname: Park
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, South Korea.
authors.forename: Eun Kyung
authors.initials: EK
authors.lastname: Cho
authors.affiliation: Division of Hematooncology, Department of Internal Medicine, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, South Korea.
authors.forename: So Young
authors.initials: SY
authors.lastname: Yoon
authors.affiliation: Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Hematology/Oncology, Department of Internal Medicine, SMG-SNU Boramae Medical Center, Seoul, South Korea.
authors.forename: In Sil
authors.initials: IS
authors.lastname: Choi
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Ulsan University Hospital, Ulsan, South Korea.
authors.forename: Jae Hoo
authors.initials: JH
authors.lastname: Park
authors.affiliation: Division of Hemato-oncology, Department of Internal Medicine, Pusan National University Hospital, Busan, South Korea.
authors.forename: Young Jin
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Division of Hematology/Medical Oncology, Department of Internal Medicine, Chung-Ang University Hospital, Seoul, South Korea.
authors.forename: Hee-Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Kyung Hae
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Division of Medical Oncology/Hematology, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, South Korea.
authors.forename: Si-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. ohdoyoun@snu.ac.kr.|Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. ohdoyoun@snu.ac.kr.
authors.forename: Do-Youn
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, Seoul, South Korea. moisa@snu.ac.kr.|Department of Internal Medicine, Seoul National University Hospital, Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, South Korea. moisa@snu.ac.kr.
authors.forename: Seock-Ah
authors.initials: SA
authors.lastname: Im
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods*; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; C455861:pegfilgrastim; D011092:Polyethylene Glycols; C423652:pegylated granulocyte colony-stimulating factor; D000069585:Filgrastim
keywords: Breast cancer; Chemotherapy-induced neutropenia; Pegteograstim; Pegylated G-CSF; Prophylaxis