他拉唑帕尼用于晚期血液系统恶性肿瘤患者的I期试验。
A Phase I trial of talazoparib in patients with advanced hematologic malignancies.
作者信息
Gopal Ajay K, Popat Rakesh, Mattison Ryan J, Menne Tobias, Bloor Adrian, Gaymes Terry, Khwaja Asim, Juckett Mark, Chen Ying, Cotter Matthew J, Mufti Ghulam J
机构信息
Division of Medical Oncology, Department of Medicine, University of Washington, Seattle, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
National Institute for Health Research University College London Hospitals Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK.
出版信息
Int J Hematol Oncol. 2021 Oct 22;10(3):IJH35. doi: 10.2217/ijh-2021-0004. eCollection 2021 Sep.
AIM
The objective of this study was to establish the maximum tolerated dose (MTD), safety, pharmacokinetics, and anti-leukemic activity of talazoparib.
PATIENTS & METHODS: This Phase I, two-cohort, dose-escalation trial evaluated talazoparib monotherapy in advanced hematologic malignancies (cohort 1: acute myeloid leukemia/myelodysplastic syndrome; cohort 2: chronic lymphocytic leukemia/mantle cell lymphoma).
RESULTS
Thirty-three (cohort 1: n = 25; cohort 2: n = 8) patients received talazoparib (0.1-2.0 mg once daily). The MTD was exceeded at 2.0 mg/day in cohort 1 and at 0.9 mg/day in cohort 2. Grade ≥3 adverse events were primarily hematologic. Eighteen (54.5%) patients reported stable disease.
CONCLUSION
Talazoparib is relatively well tolerated in hematologic malignancies, with a similar MTD as in solid tumors, and shows preliminary anti leukemic activity.Clinical trial registration: NCT01399840 (ClinicalTrials.gov).
目的
本研究的目的是确定他拉唑帕利的最大耐受剂量（MTD）、安全性、药代动力学和抗白血病活性。
患者与方法
这项I期、双队列、剂量递增试验评估了他拉唑帕利单药治疗晚期血液系统恶性肿瘤（队列1：急性髓系白血病/骨髓增生异常综合征；队列2：慢性淋巴细胞白血病/套细胞淋巴瘤）的疗效。
结果
33例患者（队列1：n = 25；队列2：n = 8）接受了他拉唑帕利治疗（每日一次，剂量为0.1 - 2.0毫克）。队列1中，2.0毫克/天的剂量超过了最大耐受剂量；队列2中，0.9毫克/天的剂量超过了最大耐受剂量。≥3级不良事件主要为血液学不良反应。18例（54.5%）患者病情稳定。
结论
他拉唑帕利在血液系统恶性肿瘤中耐受性相对良好，最大耐受剂量与实体瘤相似，并显示出初步的抗白血病活性。临床试验注册号：NCT01399840（ClinicalTrials.gov）。
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