Faculty, Staff and Student Publications
Publication Date
3-1-2024
Journal
Cancer
Abstract
Background: This study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of 8-chloro-adenosine (8-Cl-Ado) in patients with relapsed/refractory acute myeloid leukemia (AML).
Methods: 8-Cl-Ado was administered daily for 5 days; the starting dose was 100 mg/m2 , the highest dose tested was 800 mg/m2 . The end points were toxicity, disease response, and PK/PD measurements.
Results: The predominant nonhematologic toxicity was cardiac with grade ≥3 toxicity. Plasma PK in all patients suggested heterogeneity among patients, yet, some dose-dependency for the accumulation of 8-Cl-Ado. Two 8-Cl-Ado metabolites accumulated at similar levels to 8-Cl-Ado. Cellular PK in eight patients indicated accumulation of 8-Cl-ATP, which was associated with AML blast cytoreduction in peripheral blood. The authors determined the RP2D of 8-Cl-Ado to be 400 mg/m2 .
Conclusions: Given the cardiac adverse events observed, patients require monitoring for arrhythmias and QT interval during infusion. Although peripheral blood cytoreduction was observed, responses were transient, suggesting combination strategies will be required.
Keywords
Humans, Leukemia, Myeloid, Acute, 2-Chloroadenosine, 8-chloro-adenosine, phase 1, AML, 8-Cl-ATP, nucleoside analog
DOI
10.1002/cncr.35077
PMID
37897709
PMCID
PMC11687610
PubMedCentral® Posted Date
3-1-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
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