Clin Cancer Res: Zotiraciclib combined with temozolomide in the treatment of recurrent high-grade astrocytoma

The treatment of brain tumors is challenging, mainly due to its biological characteristics, including high heterogeneity and complex drug resistance mechanisms
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Only a small number of drugs that have passed clinical trials have become established therapies, emphasizing the importance of preclinical research to study promising drug candidates, thereby increasing the chances of successful drug development

This study aims to explore the toxicity characteristics of Zotiraciclib combined with temozolomide for recurrent high-grade astrocytoma and to determine the best dosing regimen
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The toxicity characteristics of Zotiraciclib combined with temozolomide for recurrent high-grade astrocytoma and the determination of the best dosing regimen

This is a two-stage phase I trial that uses Bayesian optimal interval design to determine the maximum tolerated dose (MTD) of Zotiraciclib and dose-intensive (Arm1) or rhythmic (Arm2) temozolomide; then expand at random The cohort compared the progression-free survival rate (PFS4) of the two groups at 4 months
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The change of ANC (A) and the concentration of Zotiraciclib (B) during each patient's treatment

The change of ANC (A) and the concentration of Zotiraciclib (B) during each patient's treatment

A total of 53 patients were recruited with dose-limiting toxicities such as neutropenia, diarrhea, elevated liver enzymes, and fatigue
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In both treatment arms, Zotiraciclib had an MTD of 250 mg and was therefore selected for the extended cohort

Dose-limiting toxicities include neutropenia, diarrhea, elevated liver enzymes, and fatigue.

Correlation between CYP1A2(rs2470890) polymorphism and the AUC _inf value of Zotiraciclib

Correlation between CYP1A2(rs2470890) polymorphism and the AUC _inf value of Zotiraciclib _inf

In both treatment arms, the symptom burden worsened during the second course of treatment, and stabilized again during the fourth course of treatment
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12-24 hours after oral administration of Zotiraciclib, the absolute neutrophil count and the production of neutrophil reactive oxygen species were significantly reduced, but both recovered after 72 hours

12-24 hours after oral Zotiraciclib, absolute neutrophil counts and neutrophil ROS generation cells were significantly reduced, but recovered after 72 hours _inf

In summary, Zotiraciclib combined with temozolomide is safe for the treatment of recurrent high-grade astrocytoma
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Neutropenia caused by Zotiraciclib can be severe, but most of it is short-lived and requires close monitoring rather than stopping treatment

Zotiraciclib combined with temozolomide is safe for the treatment of recurrent high-grade astrocytoma

Original source:

Jing Wu, et al.

Phase I Study of Zotiraciclib in Combination with Temozolomide for Patients with Recurrent High-grade Astrocytomas in this message