Hesketh Paul J, Arena Francis, Patel Dhimant, Austin Matt, D'Avirro Paul, Rossi Gregory, Colowick Alan, Schwartzberg Lee, Bertoli Luigi F, Cole John T, Demetri George, Dessypris Emmanuel, Dobbs Tracy, Eisenberg Peter, Fleischman Roger, Hall James, Hoffman Phillip C, Laber Damian A, Leonard John, Lester Eric P, McCachren Spence, McMeekin Scott, Meza Luis, Miller David Scott, Nand Sucha, Oliff Ira, Paroly Warren, Pawl Larry, Perez Alejandra, Raftopoulos Harry, Rigas James, Rowland Kendrith, Scullin Daniel C, Tezcan Haluk, Waples John, Ward John, Yee Lorrin K
Division of Hematology and Medical Oncology, Caritas St. Elizabeth's Medical Center, Boston, Massachusetts 02135, USA.
Cancer. 2004 Feb 15;100(4):859-68. doi: 10.1002/cncr.11954.
The effect of using fixed versus weight-based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight-based dose using an accelerated correction and maintenance dosing regimen (front-loading).
During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325 microg (n = 122) or at a weight-based dose of 4.5 microg/kg (n = 120) once weekly until they achieved a hemoglobin concentration > or = 12.0 g/dL. Patients then received darbepoetin alfa (325 microg or 4.5 microg/kg) once every 3 weeks for the remainder of the 16-week treatment period (maintenance phase).
Darbepoetin alfa resulted in high Kaplan-Meier rates of hematopoietic response (> or = 2 g/dL increase from the baseline level or a hemoglobin level > or = 12 g/dL) in both the fixed-dose group (86%; 95% confidence interval [95% CI], 78- 94%) and the weight-based dose group (84%; 95% CI, 76-92%). The median time to hematopoietic response was 34 days (95% CI, 28-44 days) for the fixed-dose group and 36 days (95% CI, 30-45 days) for the weight-based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight-based doses were observed.
Darbepoetin alfa was effective when administered as either a fixed dose or a weight-based dose using a front-loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease.
此前尚未报道过使用固定剂量与基于体重的剂量给予促红细胞生成剂的效果。为研究该问题，作者进行了一项随机II期研究，采用加速纠正和维持给药方案（预负荷），将达贝泊汀α以固定剂量或基于体重的剂量给药。
在纠正阶段，患有非髓系恶性肿瘤且正在接受化疗的贫血患者（血红蛋白<11.0 g/dL），每周一次接受325微克固定剂量的达贝泊汀α（n = 122）或4.5微克/千克基于体重的剂量（n = 120），直至血红蛋白浓度≥12.0 g/dL。然后，在为期16周的治疗期（维持阶段）剩余时间里患者每3周接受一次达贝泊汀α（325微克或4.5微克/千克）。
在固定剂量组（86%；95%置信区间[95%CI]，78 - 94%）和基于体重的剂量组（84%；95%CI，76 - 92%）中，达贝泊汀α均导致较高的造血反应的Kaplan-Meier率（较基线水平增加≥2 g/dL或血红蛋白水平≥12 g/dL）。固定剂量组达到造血反应的中位时间为34天（95%CI，28 - 44天），基于体重的剂量组为36天（95%CI，30 - 45天）。两组血红蛋白浓度均维持在目标水平长达16周。达贝泊汀α耐受性良好，未观察到固定剂量和基于体重的剂量之间存在临床显著差异。
采用预负荷方法给予达贝泊汀α时，无论是固定剂量还是基于体重的剂量，在患有恶性疾病的贫血患者中，均可有效快速纠正贫血并有效维持血红蛋白水平。
