期刊
JOURNAL OF CANCER
卷 14, 期 7, 页码 1151-1156出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.81795
关键词
venetoclax; pharmacokinetics; blood-brain barrier; cerebrospinal fluid; central nervous system
类别
Infiltration of malignant cells into the central nervous system is associated with poor clinical outcomes in hematological malignancies. Limited investigations have been conducted on the penetration of venetoclax into the central nervous system. This study demonstrates the ability of venetoclax to cross into the central nervous system and provides evidence of its potential role in improving clinical outcomes for patients with CNS complications.
Infiltration of malignant cells into the central nervous system in hematological malignancies correlates with poor clinical outcomes. Investigations into the penetration of venetoclax into the central nervous system have been limited. We report venetoclax pharmacokinetics in plasma and cerebrospinal fluid samples from a Phase 1 study in pediatric patients with relapsed or refractory malignancies that demonstrate venetoclax ability to cross into the central nervous system. Venetoclax was detected in cerebrospinal fluid (CSF) samples, with concentrations ranging from < 0.1 to 26 ng/mL (mean, 3.6 ng/mL) and a plasma:CSF ratio ranging from 44 to 1559 (mean, 385). Plasma:CSF ratios were comparable among patients with AML and ALL and no clear trend was observed in the ratios over the course of treatment. Moreover, improvement in central nervous system (CNS) involvement status was observed in patients who had measurable concentrations of venetoclax in the CSF. CNS resolution was observed for up to six months while on treatment. These findings highlight the potential role of venetoclax and provide the opportunity to further investigate its utility in improving clinical outcomes for patients with CNS complications.
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