Initial clinical trial and pharmacokinetics of Thymitaq (AG337) by 10-day continuous infusion in patients with advanced solid tumors

Cancer Chemotherapy and Pharmacology
P J CreavenM Dixon

Abstract

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. 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. 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. Continuous 10-day infusions of Thymitaq should be limited to low doses until further studies can be done.

Citations

Nov 30, 2002·Expert Opinion on Investigational Drugs·Norman L Lehman
Oct 19, 2012·PloS One·Shu-Fu LinRichard J Wong
Jun 6, 2012·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·O M AhmedS M Abd El-Tawab
Nov 28, 2012·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·R G Ahmed, S Incerpi
Jul 20, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Robert G GishGerard T Kennealey
Jan 31, 2002·Journal of Chromatography. B, Biomedical Sciences and Applications·F M Rubino

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