Abstract
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 ThymitaqTM. 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 × 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.
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Received: 4 March 1997 / Accepted: 14 July 1997
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Creaven, P., Pendyala, L., Meropol, N. et al. Initial clinical trial and pharmacokinetics of ThymitaqTM (AG337) by 10-day continuous infusion in patients with advanced solid tumors. Cancer Chemother Pharmacol 41, 167–170 (1997). https://doi.org/10.1007/s002800050724
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DOI: https://doi.org/10.1007/s002800050724