Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial
YANG Wen-Yu, LIU Tian-Feng, CHEN Xiao-Juan, GUO Ye, LI Ting, QI Ben-Quan, LIU Fang, CHANG Li-Xian, RUAN Min, LIU Xiao-Ming, ZHANG Li, ZOU Yao, CHEN Yu-Mei, ZHU Xiao-Fan
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology&Blood Diseases Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College, Tianjin 300020, China
Abstract Objective To study the pharmacokinetic characteristics, clinical effect, and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in children with acute lymphoblastic leukemia (ALL). Methods A prospective study was performed on children with ALL who cyclophosphamide, cytarabine, and 6-mercaptopurine were used for consolidation therapy. PEG-rhG-CSF (PEG-rhG-CSF group) or rhG-CSF (rhG-CSF group) was injected after chemotherapy. The plasma concentration of PEG-rhG-CSF was measured, and clinical outcome and safety were observed for both groups. Results A total of 17 children with ALL were enrolled, with 9 children in the PEG-rhG-CSF group and 8 children in the rhG-CSF group. In the PEG-rhG-CSF group, the peak concentration of PEG-rhG-CSF was 348.2 ng/mL (range 114.7-552.0 ng/mL), the time to peak was 48 hours (range 12-72 hours), and the half life was 14.1 hours (range 11.1-18.1 hours). The plasma concentration curve of PEG-rhG-CSF was consistent with the mechanism of neutrophil-mediated clearance. Compared with the rhG-CSF group, the PEG-rhG-CSF group had a significantly shorter median time to absolute neutrophil count (ANC) recovery (P < 0.05). There were no significant differences between the two groups in ANC nadir, incidence rate of febrile neutropenia, duration of grade IV neutropenia, incidence rate of infection, and length of hospital stay. No bone pain or muscle soreness was observed in either group (P > 0.05). Conclusions The pharmacokinetic characteristics of PEG-rhG-CSF in children with ALL receiving consolidation chemotherapy are consistent with the mechanism of neutrophil-mediated clearance, with a short half life and fast recovery of ANC, and there are no significant differences in safety between PEG-rhG-CSF and rhG-CSF.
YANG Wen-Yu,LIU Tian-Feng,CHEN Xiao-Juan et al. Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial[J]. CJCP, 2020, 22(11): 1172-1177.
YANG Wen-Yu,LIU Tian-Feng,CHEN Xiao-Juan et al. Pharmacokinetics and pharmacodynamics of pegylated recombinant human granulocyte colony-stimulating factor in children with acute lymphoblastic leukemia: a prospective control trial[J]. CJCP, 2020, 22(11): 1172-1177.
Welte K, Gabrilove J, Bronchud MH, et al. Filgrastim (r-metHuG-CSF):the first 10 years[J]. Blood, 1996, 88(6):1907-1929.
[2]
Ozer H, Armitage JO, Bennett CL, et al. 2000 update of recommendations for the use of hematopoietic colony-stimulating factors:evidence-based, clinical practice guidelines. American Society of Clinical Oncology Growth Factors Expert Panel[J]. J Clin Oncol, 2000, 18(20):3558-3585.
[3]
Lally J, Malik S, Whiskey E, et al. Clozapine-associated agranulocytosis treatment with granulocyte colony-stimulating factor/granulocyte-macrophage colony-stimulating factor:a systematic review[J]. J Clin Psychopharmacol, 2017, 37(4):441-446.
[4]
Kuwabara T, Kobayashi S, Sugiyama Y. Pharmacokinetics and pharmacodynamics of a recombinant human granulocyte colony-stimulating factor[J]. Drug Metab Rev, 1996, 28(4):625-658.
[5]
Green MD, Koelbl H, Baselga J, et al. A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy[J]. Ann Oncol, 2003, 14(1):29-35.
[6]
Kubo K, Miyazaki Y, Murayama T, et al. A randomized, double-blind trial of pegfilgrastim versus filgrastim for the management of neutropenia during CHASE(R) chemotherapy for malignant lymphoma[J]. Br J Haematol, 2016, 174(4):563-570.
[7]
Brito M, Esteves S, André R, et al. Comparison of effectiveness of biosimilar filgrastim (NivestimTM), reference Amgen filgrastim and pegfilgrastim in febrile neutropenia primary prevention in breast cancer patients treated with neo(adjuvant) TAC:a non-interventional cohort study[J]. Support Care Cancer, 2016, 24(2):597-603.
[8]
Yang BB, Kido A. Pharmacokinetics and pharmacodynamics of pegfilgrastim[J]. Clin Pharmacokinet, 2011, 50(5):295-306.
[9]
Yang BB, Savin MA, Green M. Prevention of chemotherapy-induced neutropenia with pegfilgrastim:pharmacokinetics and patient outcomes[J]. Chemotherapy, 2012, 58(5):387-398.
[10]
National Cancer Institute. Common terminology criteria for adverse events (CTCAE) version 4.0[EB/OL]. (2009-05-28)[2020-04-20]. https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03/Archive/CTCAE_4.0_2009-05-29_QuickReference_8.5x11.pdf.
[11]
Johnston E, Crawford J, Blackwell S, et al. Randomized, dose-escalation study of SD/01 compared with daily filgrastim in patients receiving chemotherapy[J]. J Clin Oncol, 2000, 18(13):2522-2528.
[12]
Spunt SL, Irving H, Frost J, et al. Phase II, randomized, open-label study of pegfilgrastim-supported VDC/IE chemotherapy in pediatric sarcoma patients[J]. J Clin Oncol, 2010, 28(8):1329-1336.
Fox E, Widemann BC, Hawkins DS, et al. Randomized trial and pharmacokinetic study of pegfilgrastim versus filgrastim after dose-intensive chemotherapy in young adults and children with sarcomas[J]. Clin Cancer Res, 2009, 15(23):7361-7367.
