A phase 1 study to evaluate the safety, pharmacology, and feasibility of continuous infusion nelarabine in patients with relapsed and/or refractory lymphoid malignancies

Autor: Prajwal C. Boddu, Jayastu Senapati, Farhad Ravandi‐Kashani, Elias J. Jabbour, Nitin Jain, Mary Ayres, Yuling Chen, Michael J. Keating, Hagop M. Kantarjian, Varsha Gandhi, Tapan M. Kadia
Rok vydání: 2022
Předmět:
Zdroj: Cancer. 129:580-589
ISSN: 1097-0142
0008-543X
DOI: 10.1002/cncr.34570
Popis: Nelarabine is a purine nucleoside analogue prodrug approved for the treatment of relapsed and refractory T-cell acute lymphoblastic leukemia (R/R T-ALL) and lymphoblastic lymphoma (T-LBL). Although effective in R/R T-ALL, significant neurotoxicity is dose-limiting and such neurotoxicity associated with nucleoside analogues can be related to dosing schedule.The authors conducted a phase 1 study to evaluate the pharmacokinetics and toxicity of nelarabine administered as a continuous infusion (CI) for 5 days (120 hours), rather than the standard, short-infusion approach.Twenty-nine patients with R/R T-ALL/LBL or T-cell prolymphocytic leukemia (T-PLL) were treated, with escalating doses of nelarabine from 100 to 800 mg/mPreliminary evaluation of continuous infusion schedule of nelarabine suggests that the safety profile is acceptable for this patient population, with clinical activity observed even at low doses and could broaden the use of nelarabine both as single agent and in combinations by potentially mitigating the risk of central nervous system toxicities.
Databáze: OpenAIRE
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