The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Leuk Res. 2014 Mar;38(3):316-22. doi: 10.1016/j.leukres.2013.12.006. Epub 2013 Dec 11.
This phase I study evaluated selective JAK2 inhibitor XL019 in 30 patients with myelofibrosis. The initial dose cohorts were 100, 200, and 300 mg orally on days 1-21 of a 28-day cycle. Central and/or peripheral neurotoxicity developed in all patients. Subsequently, patients were treated on lower doses; neurotoxicity was again observed, leading to study termination. Peripheral neuropathy resolved in 50%, and central neurotoxicity in all patients within months after therapy cessation. Myelosuppression was minimal. The terminal half-life of XL019 was approximately 21 h, with steady state reached by Day 8. International Working Group defined responses were seen in three (10%) patients.
这项 I 期研究评估了选择性 JAK2 抑制剂 XL019 在 30 例骨髓纤维化患者中的疗效。起始剂量组为 100、200 和 300mg，每天口服 1-21 天，每 28 天为一个周期。所有患者均出现中枢和/或周围神经毒性。随后，患者接受较低剂量治疗；再次观察到神经毒性，导致研究终止。外周神经病在治疗停止后数月内有 50%缓解，中枢神经毒性全部缓解。骨髓抑制最小。XL019 的终末半衰期约为 21 小时，第 8 天达到稳态。国际工作组定义的反应在 3 名（10%）患者中观察到。
