5-METHYLTETRAHYDROFOLATE OR 5-FORMYLTETRAHYDROFOLIC ACID TO MODULATE 5-FLUOROURACILS CYTOTOXIC ACTIVITY IN-VIVO - A PHASE-II STUDY IN PATIENTS WITH ADVANCED COLON-CANCER

The purpose of this study was to test the hypothesis that 5-methyltetr ahydrofolate (Me-THF), a source of reduced folates alternative to leuc ovorin, could effectively modulate 5-fluorouracil's (5-FU) cytotoxic a ctivity in patients with advanced colon cancer. A total of 23 patients were enrolled in a phase II trial; they received 5-FU as a 30-min inf usion at a dose of 370 mg/m(2) following a rapid i.v. push of 200 mg/m (2) Me-THF, both drugs being given for 5 consecutive days. Cycles were repeated every 4 weeks until disease progression. No patient achieved a complete response. In all, 4 patients showed a partial response (17 .4%), 7 developed stable disease (30.4%), and the remaining 12 (52.2%) progressed. Toxicity was acceptable and never exceeded WHO grade III intensity. According to our experience, the MeTHF/5-FU combination doe s not appear to be an effective treatment for advanced colon cancer. D espite its low toxic profile, in our opinion its wider use should be d iscouraged.