Glaspy John, Henry David, Patel Ravi, Tchekmedyian Simon, Applebaum Steve, Berdeaux Donald, Lloyd Richard, Berg Russell, Austin Matt, Rossi Greg
UCLA, School of Medicine, 100 UCLA Medical Plaza, Suite 550, Los Angeles, CA 90095-6956, USA.
Eur J Cancer. 2005 May;41(8):1140-9. doi: 10.1016/j.ejca.2005.01.021. Epub 2005 Apr 8.
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 mug/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 1 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.
在肿瘤学实践中引入长效促红细胞生成剂，需要了解化疗与这些促红细胞生成素的药代动力学及血液学效应之间的相互作用。我们报告了一项随机试验的结果，该试验比较了每3周给贫血的癌症化疗患者一次皮下注射6.75μg/kg的聚乙二醇化促红细胞生成素α，给药时间相对于每3周一次的化疗，分为异步给药（第15天）或同步给药（第1天）时的血液学效应。共有81例患者被随机分组并接受研究药物治疗（43例异步给药；38例同步给药）。治疗6周后，两组在主要终点指标平均血红蛋白变化方面未观察到差异（P = 0.45），变化分数与标准每周一次聚乙二醇化促红细胞生成素α治疗时观察到的相似。在一组通过密集药代动力学采样评估的患者中，两组在化疗给药后均观察到内源性促红细胞生成素浓度升高（高达4倍），持续约1周。与异步给药相比，聚乙二醇化促红细胞生成素α同步给药时其浓度-时间曲线下面积增加了1.3倍。我们的数据表明，无论相对于化疗的给药时间如何，每3周一次给予聚乙二醇化促红细胞生成素α都是有效的，并且红细胞生成素受体介导的摄取可能是促红细胞生成蛋白的一种重要清除机制。
