A combination of 5-fluorouracil and thymidine in advanced colorectal carcinoma

Concurrent administration of thymidine (TdR) has been shown to increase the antitumor activity of 5-fluorouracil (5-FU) in various experimental models. The clinical response rate, side-effects, and toxicity of 5-FU and TdR were evaluated in 27 patients with advanced colorectal carcinomas. Each 6-day treatment course consisted of an IV loading dose of TdR (405 mg/kg, over 30 min), followed by continuous IV infusions of 5-FU (7.5 mg/kg per day for 5 days), and TdR (216 mg/kg per day for 6 days); courses were repeated every 4 weeks. The overall partial response rate was 4.5%, or 16.7% in patients with no prior 5-FU chemotherapy. Short-lived stable disease was seen at an overall rate of 27.3%, half of these patients with prior 5-FU chemotherapy. Myelotoxicity occurred in 64% of the patients, but this was dose-limiting in only 20%. Gastrointestinal and neurological symptoms were mild and infrequent. There was one case of treatment-related death due to sepsis secondary to leukopenia. It is concluded that the concurrent IV administration of 5-FU and TdR does not improve the response rate over that obtained with 5-FU alone.