Pharmacology and toxicology of alpha-2'-deoxythioguanosine in cancer patients.

alpha-2'-Deoxythioguanosine (alpha-TGdR) was administered as a single dose to 13 cancer patients in 18 experiments at dose levels of 150--1500 mg/m2 and as a daily dose to 22 patients in 42 experiments at dose levels of 100--4000 mg/m2/day X 5 days. No significant toxicity was observed. Blood levels and rates of excretion were determined with radiosulfur-labeled alpha-TGdR. Approximately 80% of the dose was excreted in the urine in 24 hours, initially as unchanged alpha-TGdR and increasingly as metabolites. Metabolites appear to be nucleosides and do not include 6-thioguanine, 6-thioxanthine, or 6-thiouric acid to any measurable extent. Small amounts of the alpha-TGdR in blood samples were bound to albumin and to erythrocyte membranes. Blood plasma levels of alpha-TGdR at the highest doses were in the range of 200--300 micrometer, declining in 24 hours to 67--124 micrometer.