Phase II study with high-dose N5-10-methyltetrahydrofolate and 5-fluorouracil in advanced colorectal cancer

Thirty-eight patients with advanced colorectal adenocarcinoma were treated with the following regimen: N^5-10-methyltetrahydrofolate (MTHF) (200 mg/m²/day) and 5-fluorouracil (5-FU) (375 mg/m²/day) given concomitantly, consecutively for 5 days, every 4 weeks, in order to evaluate the potential advantage derived from the biochemical enhancement of cytotoxic activity of 5-FU by high-dose reduced folates. Of 33 evaluable patients (six of whom had received prior 5-FU chemotherapy) three untreated patients achieved a partial response (9.1%) lasting 84, 281 and 401 days; 24 patients (72.7%) had stable disease lasting a median of 150 days (range 60-304 days). The overall toxicity was acceptable: two patients had severe cardiac symptoms. Pharmacokinetics and biochemical studies seem necessary to determine the optimal dosage and timing of 5-FU and folates.