A less toxic regimen of 5-fluorouracil and high-dose folinic acid for advanced gastrointestinal adenocarcinomas

Abstract

The combination of high-dose folinic acid with 5-fluorouracil has shown improved response rates in several trials in advanced colorectal carcinoma. This however is at the expense of increased toxicity: regimens using weekly bolus injections produce diarrhoea in most patients and occasional toxic deaths from this, whilst those using daily injections for one week in four report both diarrhoea and severe oral mucositis. Both types of regimen have significant rates of myelosuppression. A recent report described a different schedule of 5-fluorouracil and folinic acid, which appeared better tolerated but equally active (De Gramont et al., 1988). Here we report results using the same programme, in 64 patients with advanced adenocarcinomas. (Forty three colorectal, ten gastric, six pancreatic and five of unknown primary.) Patients received 200 mg m-2 folinic acid by infusion over 2 h followed by an IV bolus of 5-fluorouracil 400 mg m-2 then an infusion of 5-fluorouracil 400 mg m-2 over 22 h. This was repeated over the next 24 h. The schedule was given every 2 weeks for a total of six to 12 courses depending upon the response. The overall response rate was 26% in 62 evaluable patients. No toxicity greater than WHO Grade II occurred. Diarrhoea and mucositis did occur in around 10% of treatments but were not troublesome. No febrile neutropenic episodes were seen. Despite previous reports which described only modest activity for this combination against stomach cancers, this regimen demonstrates low toxicity but retains good activity in the palliative treatment of both gastric and colonic adenocarcinomas.