West Clinic, Memphis, TN, USA.
BMC Cancer. 2010 Oct 25;10:581. doi: 10.1186/1471-2407-10-581.
BACKGROUND: Chemotherapy-induced anemia (CIA) is responsive to treatment with erythropoiesis-stimulating agents (ESAs) such as darbepoetin alfa. Administration of ESAs on a synchronous schedule with chemotherapy administration could benefit patients by reducing clinic visits and potentially enhancing on-time chemotherapy delivery. METHODS: This phase 2, 25-week, open-label study evaluated the noninferiority of darbepoetin alfa administered weekly vs. as an extended dosing schedule (every 2 or 3 weeks) in patients with CIA. Patients were randomized 1:1 to an extended dosing schedule (EDS: darbepoetin alfa 300 μg Q2W if chemotherapy was QW, Q2W, or Q4W or darbepoetin alfa 500 μg Q3W if chemotherapy was Q3W) or weekly (150 μg QW regardless of chemotherapy schedule). Stratification factors included chemotherapy cycle length, screening hemoglobin (<10 g/dL vs. ≥10 g/dL), and tumor type (lung/gynecological vs. other nonmyeloid malignancies). The primary endpoint was change in hemoglobin from baseline to Week 13. RESULTS: Seven hundred fifty-two patients (374 QW patients; 378 EDS patients) received ≥1 dose of darbepoetin alfa and were included in the analysis. Demographics and disease state were similar between groups. Seventy-one percent of patients in the EDS group and 76% in the QW group achieved the target hemoglobin of ≥11.0 g/dL. There was a minimal difference in the primary endpoint of mean change in hemoglobin (baseline to Week 13) between the QW and the EDS groups (-0.04 g/dL; 95% confidence interval: -0.26, 0.17 g/dL). The upper limit of the 95% confidence interval was less than the prespecified limit of <0.75 g/dL, supporting noninferiority of the EDS dosing schedule. Reported adverse events were similar between groups. A slight increase in transfusions was reported in the QW group. CONCLUSION: Darbepoetin alfa, when administered synchronously with chemotherapy, on an EDS appears to be similarly efficacious to darbepoetin alfa weekly dosing with no unexpected adverse events. This study provides prospective data on how multiple dosing regimens available with darbepoetin alfa can be synchronized with chemotherapy administered across a range of dosing schedules. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00144131.
背景：化疗引起的贫血（CIA）对促红细胞生成素刺激剂（ESA）如达贝泊汀α的治疗有反应。ESA 与化疗同步给药可以通过减少就诊次数并有可能提高按时化疗的递送，从而使患者受益。
方法：这项为期 25 周的 2 期、开放标签研究评估了 CIA 患者每周给予达贝泊汀α与延长给药方案（每 2 或 3 周一次）的非劣效性。患者以 1:1 的比例随机分为延长给药方案组（EDS：如果化疗为每周、每 2 周或每 4 周一次，则给予达贝泊汀α 300μg Q2W；如果化疗为每 3 周一次，则给予达贝泊汀α 500μg Q3W）或每周给药组（150μg QW，不论化疗方案如何）。分层因素包括化疗周期长度、筛查时的血红蛋白（<10g/dL 与≥10g/dL）和肿瘤类型（肺部/妇科与其他非髓性恶性肿瘤）。主要终点为从基线到第 13 周时的血红蛋白变化。
结果：752 名患者（374 名 QW 患者；378 名 EDS 患者）接受了至少一剂达贝泊汀α，并纳入分析。两组的人口统计学和疾病状况相似。EDS 组 71%的患者和 QW 组 76%的患者达到了≥11.0g/dL 的目标血红蛋白。QW 组和 EDS 组的主要终点（从基线到第 13 周的平均血红蛋白变化）之间的差异很小（-0.04g/dL；95%置信区间：-0.26，0.17g/dL）。95%置信区间的上限低于预设的<0.75g/dL 限值，支持 EDS 给药方案的非劣效性。两组报告的不良事件相似。QW 组报告输血略有增加。
结论：达贝泊汀α与化疗同步给药时，EDS 方案似乎与每周给药方案同样有效，且无意外不良事件。这项研究提供了关于达贝泊汀α的多种可用给药方案如何与各种剂量方案的化疗同步的前瞻性数据。
临床试验注册：ClinicalTrials.gov 标识符 NCT00144131。
Front Immunol. 2014-11-11
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