BOLUS INFUSIONAL 5-FLUOROURACIL AND FOLINIC ACID FOR METASTATIC COLORECTAL-CARCINOMA - ARE SUBOPTIMAL DOSAGES BEING USED IN THE UK/

Bolus/infusional 5-fluorouracil (5-FU) and folinic acid (FA) is report ed to be highly active [partial response (PR) = 54%, median survival 1 8 months] in patients with metastatic colorectal carcinoma (MCCa). To confirm this level of activity, we conducted a retrospective analysis of 95 previously untreated patients with MCCa treated with FA by 2 h i .v. infusion (200 mg m(-2)) followed by 5-FU bolus/22 h i.v. infusion (300-500 mg m(-2)) on days 1 and 2 every 2 weeks. Thirty patients also received N-(phosphonacetyl)-L-aspartate (PALA), 250 mg m(-2), 24 h pr ior to 5-FU/FA. In 81 evaluable patients, the response rate was low: P R = 11%, stable disease (SD)= 36% and median survival = 8 months. Ther e was an improvement in survival with increased 5-FU dosage (500 mg m( -2)) [relative hazard (RH) = 0.38, 95% CI 0.21-0.70], controlled for a ge, primary site, PALA, liver function and performance status. Good pe rformance status (PS 0 or 1) was also associated with improved surviva l (RH = 0.21, 95% CI 0.10-0.46). Response, survival and toxicity were not altered by the co-administration of PALA. Bolus/infusional 5-FU (5 00 mg m(-2)) and FA was well tolerated. WHO toxicities (grade 3) were: mucositis, 2%; diarrhoea, 14%; nausea and vomiting, 5%. In light of t he apparent dose effect, poor response and low toxicity, we recommend that regimes incorporating higher 5-FU dosages are explored and prospe ctively validated before bolus/infusional 5-FU becomes accepted standa rd practice.