Glaspy John, Gabrail Nashat Y, Locantore-Ford Patricia, Lee Tyson, Modelska Katharina, Samal Vivek, Henry David H
Department of Medicine, University of California Los Angeles School of Medicine, Los Angeles, California, USA.
Department of Oncology, Gabrail Cancer Center, Canton, Ohio, USA.
Am J Hematol. 2023 May;98(5):703-711. doi: 10.1002/ajh.26865. Epub 2023 Feb 24.
Anemia is a common side effect of myelosuppressive chemotherapy; however, chemotherapy-induced anemia (CIA) management options are suboptimal. We evaluated the efficacy and safety of roxadustat in this setting. This open-label Phase 2 study included patients with non-myeloid malignancies and CIA (hemoglobin [Hb] ≤10 g/dL) who had planned concurrent myelosuppressive chemotherapy for ≥8 additional weeks. Oral roxadustat was administered for ≤16 weeks (starting dose 2.0 or 2.5 mg/kg, then titrated every 4 weeks). The primary efficacy endpoint was mean maximum change in Hb within 16 weeks of baseline without red blood cell (RBC) transfusion. Patients were assigned to roxadustat 2.0 (n = 31) or 2.5 mg/kg (n = 61) starting doses, and 89 were assessed for efficacy. The mean (standard deviation) maximum Hb change from baseline without RBC transfusion was 2.4 (1.5) and 2.5 (1.5) g/dL in the roxadustat 2.0 and 2.5 mg/kg groups, respectively. Median (range) time to Hb increase of ≥2 g/dL was 71 (57-92) days. Twelve patients (14.5%) had RBC transfusions (Week 5 to the end of treatment). Roxadustat was efficacious regardless of tumor type and chemotherapy regimen. Deep vein thrombosis (DVT) and pulmonary embolism (PE) occurred in 14 (15.2%) and nine (9.8%) patients, respectively, and three had serious adverse events attributed to roxadustat in the opinion of the investigators (PE: n = 2 [2.2%]; DVT: n = 1 [1.1%]). Roxadustat increased Hb in patients with CIA regardless of tumor type and chemotherapy regimen. Adverse events were consistent with observations in patients with advanced-stage malignancies.
贫血是骨髓抑制性化疗常见的副作用；然而，化疗所致贫血（CIA）的管理方案并不理想。我们评估了罗沙司他在此种情况下的疗效和安全性。这项开放标签的2期研究纳入了患有非髓系恶性肿瘤和CIA（血红蛋白[Hb]≤10 g/dL）且计划进行至少8周同步骨髓抑制性化疗的患者。口服罗沙司他的疗程≤16周（起始剂量为2.0或2.5 mg/kg，然后每4周调整一次剂量）。主要疗效终点是在不进行红细胞（RBC）输注的情况下，基线后16周内Hb的平均最大变化。患者被分配至罗沙司他起始剂量为2.0（n = 31）或2.5 mg/kg（n = 61）组，共89例患者接受了疗效评估。在不进行RBC输注的情况下，罗沙司他2.0和2.5 mg/kg组中，Hb相对于基线的平均（标准差）最大变化分别为2.4（1.5）和2.5（1.5）g/dL。Hb升高≥2 g/dL的中位（范围）时间为71（57 - 92）天。12例患者（14.5%）接受了RBC输注（第5周直至治疗结束）。无论肿瘤类型和化疗方案如何，罗沙司他均有效。分别有14例（15.2%）和9例（9.8%）患者发生深静脉血栓形成（DVT）和肺栓塞（PE），研究者认为有3例发生了与罗沙司他相关的严重不良事件（PE：n = 2 [2.2%]；DVT：n = 1 [1.1%]）。无论肿瘤类型和化疗方案如何，罗沙司他均可提高CIA患者的Hb水平。不良事件与晚期恶性肿瘤患者的观察结果一致。
