Bolus/infusional 5-fluorouracil and folinic acid for metastatic colorectal

Sunmary Bolus infusional 5-fluorouracil (5-FU) and folinic acid (FA) is reported to be highly active [partial response (PR) = 54%, median survival 18 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-) followed by 5-FU bolus/22 h i.v. infusion (300-500mg m-) on days 1 and 2 every 2 weeks. Thirty patients also received N-phosphonacetyl)-L-aspartate (PALA). 250mg m- 24 h prior to 5-FU FA. In 81 evaluable patients, the response rate was low: PR = 11%, stable disease (SD) = 36 % and median survival = 8 months. There was an improvement in survival with incresed 5-FU dosage (500 mg m-) [relative hazard (RH) = 0.38, 95 % CI 0.21-0.70], controlled for age, primary site, PALA, liver function and performance status. Good performance status (PS 0 or 1) was also associated with improved survival (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 (500 mg m-2) and FA was well tolerated. WHO toxicities (grade 3) were: mucositis, 2%; diarrhoea, 14%; nausea and vomiting, 5%. In light of the apparent dose effect. poor response and low toxicity, we recommend that regimes incorporating higher 5-FU dosages are explored and prospectively validated before bolus infusional 5-FU becomes accepted standard practice