Phase I study of thymidine plus 5-fluorouracil infusions in advanced colorectal carcinoma

In order to determine the minimal toxic dose of a 5-day infusion of 5-fluorouracil (5--FU) in combination with an infusion of thymidine (TdR), 12 patients, received TdR at a dose of 8 g/m2/day for 5 1/2 days, beginning at the same time as a 5-day infusion of 5-FU at doses of 5--20 mg/kg/day. Myelosuppression was the dose-limiting toxicity, and the minimal toxic dose of 5--FU was found to be 7.5 mg/kg/day. Gastrointestinal toxicity was minimal to absent. In eight patients with carcinoma of the colon who had received no prior chemotherapy, there were two patients with partial responses (at doses of 5.0 and 7.5 mg/kg/day of 5--FU), two patients with stable disease, one patient with progressive disease, and three patients with early death (two drug-related deaths and one disease-related death). In four patients who had received prior 5--FU, one had stable disease, one had progressive disease, and two had early death (one drug-related death). We conclude that the addition of TdR to 5--FU infusions changes the dose-limiting toxicity from gastrointestinal toxicity to myelosuppression. The minimal toxic dose is decreased to approximately one third of that when 5--FU is administered alone.