Randomized trial comparing monthly low-dose leucovorin and fluorouracil bolus with weekly high-dose 48-hour continuous-infusion fluorouracil for advanced colorectal cancer: A Spanish Cooperative Group for Gastrointestinal Tumor Therapy (TTD) study

• Published in: Annals of oncology Vol. 9; no. 7; pp. 727 - 731
• Main Authors: Aranda, E., Díaz-Rubio, E., Cervantes, A., Antón-Torres, A., Carrato, A., Massutí, T., Tabernero, J. M., Sastre, J., Trés, A., Aparicio, J., López-Vega, J. M., Barneto, I., García-Conde, J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.07.1998
• Subjects: Adult; advanced colorectal cancer; Aged; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - therapeutic use; Antineoplastic agents; biochemical modulation; Biological and medical sciences; Chemotherapy; Colorectal Neoplasms - drug therapy; continuous infusion; Drug Administration Schedule; Female; fiuorouracil; Fluorouracil - administration & dosage; Fluorouracil - therapeutic use; Humans; Infusions, Intravenous; Injections, Intravenous; Leucovorin - administration & dosage; Male; Medical sciences; Middle Aged; Pharmacology. Drug treatments; phase III trial; Survival Analysis; Europe; Spain; Antineoplastic agent; Phase III trial; Human; Drug combination; Rectal disease; Intravenous administration; Toxicity; Multicenter study; Fluoropyrimidine derivatives; Administration schedule; Calcium folinate; Malignant tumor; Colonic disease; Chemotherapy; Randomization; Treatment; Rectum; Digestive diseases; Intestinal disease; Pyrimidine derivatives; Colon; Fluorouracil
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1023/A:1008282824860

Purpose The objective of this multicenter study was to compare the efficacy and toxicity profiles of a combination of 5-fluorouracil (5-FU) given by bolus injection together with intravenous leucovorin (LV) versus high-dose 5-FU in continuous infusion (CI) in the treatment of advanced colorectal cancer. Patients and methods A total of 306 patients were randomized to receive either 5-FU 425 mg/m2 given by bolus injection on days 1–5 plus intravenous (i.v.) LV 20 mg/m2 every four to five weeks or 5-FU 3.5 g/m2/week in a 48-hour CI. Therapy was continued until disease progression. Second-line chemotherapy was allowed in both arms. Results The response rates in 306 patients with measurable lesions were 19.2% (modulated arm) and 30.3% (CI arm, P < 0.05). The median progression-free survival times were 23.5 weeks (modulated arm) and 25 weeks (CI arm, P = NS). Median survival times were 42.5 weeks (modulated arm) and 48 weeks (CI arm, P = NS). There were no significant differences in grade 3-4 toxicity profiles but if we consider all grades we observed more mucositis in the modulated arm and more hand-foot syndrome in the CI arm. Conclusions In terms of response rate, the continuous infusion regimen was more effective than the modulated regimen. There was no significant difference in survival and time to progression, and none in grade 3-4 toxicity.