Treatment of advanced colorectal and gastric adenocarcinomas with 5-fluorouracil combined with high-dose folinic acid. An update.

Sixty-six patients with advanced colorectal adenocarcinoma and 24 with advanced gastric adenocarcinoma were treated; all had measurable tumors. The treatment was based on biochemical and cell culture studies which have demonstrated that an excess of intracellular reduced folates is necessary to provide optimal inhibition of thymidylate synthetase and to increase the cytotoxic effect of fluoropyrimidines. The treatment comprised 5-fluorouracil (5-FU) (370-400 mg/m2/day) and high dose folinic acid (200 mg/m2/day) given simultaneously for 5 consecutive days with a 21-day interval between courses. Of the 66 patients with colorectal carcinoma, 44 had not been previously treated with cytostatics and 22 were resistant to previous chemotherapy with 5-FU given either as a single agent or combined with other drugs. The response rates both complete (CR) and partial (PR) were 45% and 18% in the previously untreated and the previously treated patients, respectively. Time to disease progression in the 20 previously untreated patients ranged from 2 to 34.5+ months (median, 10.3 months) and that of the 4 patients previously resistant to 5-FU was 7, 10, 12 and 15 months, respectively. Median survival for the 24 responders was 20.4 months. Survival in responders was significantly superior to that observed in patients with progressive disease (P less than 10(-8)). Of the 24 patients with gastric adenocarcinoma, 23 had not been previously treated with cytostatics and one was resistant to a 5-FU containing regimen. The response rate (CR + PR) was 50% (12 patients). The single previously treated patient failed to respond. Time to disease progression in the 12 responders ranged from 2.1 to 28.9 months (median, 5.6 months).(ABSTRACT TRUNCATED AT 250 WORDS)