5-Fluorouracil and folinic acid: a Phase I-II trial in gastrointestinal malignancy

Fifty-one patients with metastatic adenocarcinoma received Folinic Acid (FA) combined with 5-Fluorouracil (5FU) in a Phase I-II clinical trial. Two different schedules were used: (a) bolus infusion--5FU 7-12 mg/kg/d I.V. d1-5, FA 1.6 mg/kg/d I.V. d1-5; (b) continuous infusion--5FU 600-1200 mg/m2/d I.V. d1-4, FA 60 mg/m2/d I.V. d1-4. Mucositis and myelosuppression were dose-limiting, with recommended dose levels of 5FU for further trials being 10 mg/kg/d I.V. d1-5 and 1000 mg/m2/d I.V. d1-4 on the bolus and continuous infusion schedules, respectively. Forty-one evaluable patients with measurable disease were treated. Thirty-six had metastatic colorectal carcinoma, and 14/36 patients responded (CR-1, PR-13), including responses in three patients who had previously failed 5FU treatment alone. In the two patients with unknown primary sites and three with gastric cancer, no response were seen. 5FU and FA have activity equivalent to 5FU alone, and the responses in patients receiving prior 5FU suggest it may be superior. The possibility that toxicity may be enhanced does exist. Further trials of these two agents are warranted.