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Updated: Aug 18, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 19, 2013
Initial clinical trial and pharmacokinetics of Thymitaq (AG337) by 10-day continuous infusion in patients with
P J Creaven1, L Pendyala, N J Meropol
1Department of Investigational Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263-0001, USA.
Purpose:
To establish the maximum tolerated dose (MTD), dose-limiting and other major toxicities and the major pharmacokinetic parameters of a 10-day infusion of the nonclassical antifolate Thymitaq.
Methods:
The drug was given by 10-day infusion via a portable pump. The starting dose was 286 mg/m2 per day with escalation to 572 and 716 mg/m2 per day. Thymitaq in plasma was assayed by a validated isocratic reverse-phase HPLC assay with detection at 273 nm.
Results:
The dose of 716 mg/m2 per day x 10 was considered too high as none of three patients completed a 10-day infusion and two of three developed grade IV myelotoxicity. At 572 mg/m2 per day three of four patients completed a 10-day infusion. Dose-limiting myelosuppression was seen in one of four but owing to a high incidence of thrombotic phenomena, no further patients were added.
Conclusion:
Continuous 10-day infusions of Thymitaq should be limited to low doses until further studies can be done.
