A phase I study of different doses and frequencies of pegylated recombinant human granulocyte-colony

来源 :Chinese Journal of Cancer Research | 被引量 : 0次 | 上传用户:zxcvbnmzhaowei
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Objective: The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor(PEG rhG-CSF) is 100 μg/kg once per cycle for patients receiving intense-dose chemotherapy.However, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy.Methods:Eligible patients received 3-cycle chemotherapy every 3 weeks.No PEG rhG-CSF was given in the first cycle.Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3.In cycle 2,patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3,and received half-dose subcutaneous injection in cycle 3 on d 3 and d 5,respectively.Escalating doses(30,60,100 and 200μg/kg)of PEG rhG-CSF were investigated.Results:A total of 26 patients were enrolled and received chemotherapy,in which 24 and 18 patients entered cycle 2 and cycle 3 treatment,respectively.In cycle 2,the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30,60,100 and 200 μg/kg was 66.67%,33.33%,22.22% and 0,respectively,with a median duration less than 1(0–2)d.No grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts.Conclusions:The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported,as well as the safety.Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above.The single dose of 60 μg/kg,100 μg/kg and double half dose of 30 μg/kg were recommended to the phase Ⅱ study,hoping to find a preferable method for neutropenia treatment. Objective: The recommended dose of prophylactic pegylated recombinant human granulocyte-colony stimulating factor (PEG rhG-CSF) is 100 μg / kg once per cycle for patients receiving intense-dose chemotherapy. Some, few data are available on the proper dose for patients receiving less-intense chemotherapy. The aim of this phase I study is to explore the proper dose and administration schedule of PEG rhG-CSF for patients receiving standard-dose chemotherapy. Methods: Eligible patients received 3-cycle chemotherapy every 3 weeks. No PEG rhG -CSF was given in the first cycle. Patients experienced grade 3 or 4 neutropenia would then enter the cycle 2 and 3. In cycle 2, patients received a single subcutaneous injection of prophylactic PEG rhG-CSF on d 3, and received half-dose Subcutaneous injection in cycle 3 on d 3 and d 5, respectively. Ethyl acetate (30, 60, 100 and 200 μg / kg) of PEG rhG-CSF were investigated. Results: A total of 26 patients were enrolled and received chemotherapy, in which 24 and 18 p atients entered cycle 2 and cycle 3 treatment, respectively.In cycle 2, the incidence of grade 3 or 4 neutropenia for patients receiving single-dose PEG rhG-CSF of 30, 60, 100 and 200 μg / kg was 66.67%, 33.33%, 22.22 % and 0, respectively, with a medium duration less than 1 (0-2) d. Grade 3 or higher neutropenia was noted in cycle 3 in all dose cohorts. Conclusions: The pharmacokinetic and pharmacodynamic profiles of PEG rhG-CSF used in cancer patients were similar to those reported, as well as the safety. Double half dose administration model showed better efficacy result than a single dose model in terms of grade 3 neutropenia and above. single dose of 60 μg / kg, 100 μg / kg and double half dose of 30 μg / kg were recommended to the phase Ⅱ study, hoping to find a preferred method for neutropenia treatment.
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