Effects of chemotherapy on endogenous erythropoietin levels and the pharmacokinetics and erythropoietic response of darbepoetin alfa: A randomised clinical trial of synchronous versus asynchronous dosing of darbepoetin alfa

被引:61
作者
Glaspy, J
Henry, D
Patel, R
Tchekmedyian, D
Applebaum, S
Berdeaux, D
Lloyd, R
Berg, R
Austin, M
Rossi, G
机构
[1] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA
[2] Joan Karnell Canc Ctr, Philadelphia, PA USA
[3] Comprehen Blood & Canc Ctr, Bakersfield, CA USA
[4] Pacific Shores Med Grp, Long Beach, CA USA
[5] Virginia K Crosson Canc Ctr, Fullerton, CA USA
[6] Amgen Inc, Thousand Oaks, CA USA
关键词
darbepoetin alfa; pharmacokinetics; chemotherapy; erythropoietin synchronous; asynchronous;
D O I
10.1016/j.ejca.2005.01.021
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The introduction of longer-acting erythropoietic agents into the practice of oncology has demanded an understanding of the interaction of chemotherapy with the pharmacokinetics and haematological effects of these erythropoietins. We report results of a randomised trial comparing the haematological effects of darbepoetin alfa, 6.75 mu g/kg, administered once every 3 weeks to anaemic cancer chemotherapy patients on either an asynchronous (day 15) or synchronous (day 1) schedule relative to their every-3-week chemotherapy. A total of 81 patients were randomised and received the study drug (43 asynchronous; 38 synchronous). No difference was observed between groups in the primary endpoint of mean haemoglobin change after 6 weeks of therapy (P = 0.45) and change scores were similar to those observed with standard weekly darbepoetin alfa therapy. In a subset of patients evaluated with intensive pharmacokinetic sampling, an increase in endogenous erythropoietin concentration (up to 4-fold) lasting approximately I week following chemotherapy administration was observed in both groups. Synchronous administration of darbepoetin alfa was associated with a 1.3-fold increase in the area under the darbepoetin alfa concentration-time curve compared with asynchronous administration. Our data suggest that darbepoetin alfa is effective administered every 3 weeks regardless of timing of administration with respect to chemotherapy and that receptor-mediated uptake by the erythron may be an important clearance mechanism for erythropoietic proteins. (c) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1140 / 1149
页数:10
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