Clinical and biochemical studies of high-dose thymidine treatment in patients with solid tumors

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Abstract
In a clinical study of high-dose thymidine (TdR) treatment, toxic effects, TdR metabolism, and the influence of TdR on pyrimidine and purine metabolism were examined. Ten patients with solid tumors were treated with continuous infusion of TdR at 34–75 g/m2/day for 3 to 5 days. Hematologic toxicity occurred with 5-day TdR infusion at 75 g/m2/day but not when plasma TdR concentration failed to reach millimolar levels. In three patients who received similar TdR doses, plasma TdR levels were related to elimination rates of TdR and its metabolites from plasma. In one patient in whom urinary excretion was studied, 100% of the TdR dose given was recovered in the form of TdR, thymine (Thy), β-aminoisobutyrate, and 5-hydroxymethyluracil (5-HMUra). The latter metabolite, which had not been previously described in high-dose TdR treatment, was also found in plasma at levels from 5% to 10% of those of TdR. No effects of high-dose TdR infusion on purine levels in plasma were observed, while a substantial increase in uracil levels was noted both in plasma and urine. These data provide further information on high-dose TdR treatment with regard to clinical, pharmacokinetic, and biochemical effects.