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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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.[1]

References

  1. Initial clinical trial and pharmacokinetics of Thymitaq (AG337) by 10-day continuous infusion in patients with advanced solid tumors. Creaven, P.J., Pendyala, L., Meropol, N.J., Clendeninn, N.J., Wu, E.Y., Loewen, G.M., Proefrock, A., Johnston, A., Dixon, M. Cancer Chemother. Pharmacol. (1998) [Pubmed]
 
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