Volasertib as a monotherapy or in combination with azacitidine in patients with myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia: summary of three phase I studies.
Volasertib as a monotherapy or in combination with azacitidine in patients with myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia: summary of three phase I studies.
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DOI：
10.1186/s12885-022-09622-0
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发表时间：
2022-05-21
期刊：
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
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本报告总结了三个I期研究，评估volasertib（一种脊髓样激酶抑制剂）和阿扎胞苷在骨髓增生异常综合征（MDS）、慢性髓单细胞白血病或急性髓系白血病成人患者中的疗效。患者接受静脉注射volasertib，周期为28天（剂量递增计划）。在1230.33的第一部分（研究1；NCT01957644）中，患者在第(D)1天和第15天接受250-350 mg volasertib；在第2部分，患者接受不同的治疗方案[A， D1: 170 mg/m2；B、D7: 170 mg/m2；C， D1和D7: 110 mg/m2]。在1230.35（研究2；NCT02201329），患者在D1和D15接受200-300 mg volasertib。在2003年（研究3；NCT02721875），患者在D1和D8接受110 mg/m2的volasertib。研究1和研究2中的所有患者，以及研究3中大约一半的患者，计划在D1-7日接受75 mg/m2的阿扎胞苷皮下注射。总共有22名患者接受了治疗（17名MDS患者，12名此前未接受治疗）。在研究1和2中（n = 21），最常见的药物相关不良事件是血液学（血小板减少症[n = 11]；中性粒细胞减少症[n = 8]）。所有剂量限制性毒性均为4级血小板减少症。研究3中唯一接受治疗的患者在volasertib单药治疗后经历了18次不良事件。研究1和2显示了初步的活性（客观反应率：25%和40%）。volasertib与阿扎胞苷在MDS患者中的安全性与其他volasertib研究一致。勃林格殷格翰公司因非临床原因停用volasertib后，所有研究均提前终止；然而，volasertib联合阿扎胞苷的安全性信息对其他疾病的未来研究很有意义。
This report summarizes three phase I studies evaluating volasertib, a polo-like kinase inhibitor, plus azacitidine in adults with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia, or acute myeloid leukemia. Patients received intravenous volasertib in 28-day cycles (dose-escalation schedules). In Part 1 of 1230.33 (Study 1; NCT01957644), patients received 250–350 mg volasertib on day (D)1 and D15; in Part 2, patients received different schedules [A, D1: 170 mg/m2; B, D7: 170 mg/m2; C, D1 and D7: 110 mg/m2]. In 1230.35 (Study 2; NCT02201329), patients received 200–300 mg volasertib on D1 and D15. In 1230.43 (Study 3; NCT02721875), patients received 110 mg/m2 volasertib on D1 and D8. All patients in Studies 1 and 2, and approximately half of the patients in Study 3, were scheduled to receive subcutaneous azacitidine 75 mg/m2 on D1–7. Overall, 22 patients were treated (17 with MDS; 12 previously untreated). Across Studies 1 and 2 (n = 21), the most common drug-related adverse events were hematological (thrombocytopenia [n = 11]; neutropenia [n = 8]). All dose-limiting toxicities were grade 4 thrombocytopenia. The only treated patient in Study 3 experienced 18 adverse events following volasertib monotherapy. Studies 1 and 2 showed preliminary activity (objective response rates: 25 and 40%). The safety of volasertib with azacitidine in patients with MDS was consistent with other volasertib studies. All studies were terminated prematurely following the discontinuation of volasertib for non-clinical reasons by Boehringer Ingelheim; however, safety information on volasertib plus azacitidine are of interest for future studies in other diseases.
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通讯作者：
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