Bolus/infusional 5-fluorouracil and folinic acid for metastatic colorectal carcinoma: are suboptimal dosages being used in the UK?

• Published in: British journal of cancer Vol. 70; no. 4; pp. 749 - 752
• Main Authors: Jodrell, D I, Murray, L S, Reed, N S, Canney, P A, Kaye, S B, Cassidy, J
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.10.1994
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Colorectal Neoplasms - drug therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Follow-Up Studies; Humans; Infusions, Intravenous; Leucovorin - administration & dosage; Male; Middle Aged; Neoplasm Metastasis; Retrospective Studies; Survival Analysis
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.1994.389

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-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 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 increased 5-FU dosage (500 mg m-2) [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.