Abstract
Although plasma concentrations of 6-thioguanine after oral administration in man have been shown to be highly variable, 6-TG has been used almost exclusively orally in therapy of human cancers. We carried out the first Phase I trial of 6-TG given intravenously daily for 5 days in 40 patients with advanced solid tumors and normal bone marrow function. 6-TG was given by rapid IV infusion in increments ranging from a daily dose of 15 to 65 mg/m2. Dose limiting leukopenia associated with thrombocytopenia at times occurred at daily doses of 55-65 mg/m2. Several patients at these doses had no toxicity whatsoever and tolerated multiple courses of the drug without evidence of cumulative toxicity. Plasma and red cell concentrations of parent compound were similar in all individuals. No metabolites were measurable by hplc. Plasma elimination best fit a one-compartment model. The terminal half-life (t1/2) was 20 minutes on day 1 and on day 5. We (unpublished data) and Konits et al (Cancer Chemo Pharmacol 8:199, 1982) previously demonstrated that high doses of 6-TG (700 mg/m2) given IV on a single day do not consistently produce hematologic toxicity, although t1/2 is more than 10 times greater than after the doses used in this study. Preliminary statistical analyses suggest an effect of dose, prior treatment, and possibly sex on the extent of hematologic toxicity. Supported by NCI contract CM27548.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kovach, J., Hu, T. & Rubin, J. HEMATOLOGIC TOXICITY PRODUCED BY PARENTERAL 6-THIOGUANINE IN MAN IS DOSE AND SCHEDULE DEPENDENT AND HIGHLY VARIABLE IN SEVERITY: 104. Pediatr Res 19, 761 (1985). https://doi.org/10.1203/00006450-198507000-00124
Issue Date:
DOI: https://doi.org/10.1203/00006450-198507000-00124