Five-day continuous infusion of 5-fluorouracil and pulsed folinic acid in patients with metastatic colorectal carcinoma: An effective second-line regimen

• Published in: Annals of oncology Vol. 8; no. 11; pp. 1163 - 1165
• Main Authors: Streit, M., Jaehde, U., Stremetzne, S., Ridwelski, K., Kerz, H., Strohbach, F., Hohenberger, P., Zwiebel, F. M., Hebart, H., Böthig, R., Kairies, M., Zillig, D., Schuchmann, S., Warnecke, S., Thiel, E., Kreuser, E. D.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.1997
• Subjects: 5-fluorouracil; Antineoplastic agents; Biological and medical sciences; Chemotherapy; colorectal cancer; Medical sciences; Pharmacology. Drug treatments; second-line chemotherapy; Antineoplastic agent; Human; Rectal disease; Carcinoma; Intravenous administration; Toxicity; Fluoropyrimidine derivatives; Calcium folinate; Malignant tumor; Colonic disease; Chemotherapy; Limit dose; Treatment; Phase II trial; Rectum; Digestive diseases; Intestinal disease; Advanced stage; Colon; Daily dose; Fluorouracil
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1023/A:1008257603687

Objectives A previous phase I trial in 14 pretreated patients with progressive advanced colorectal cancer demonstrated 750 mg/m2 to be the maximum tolerable dose of 5-fluorouracil (5-FU) administered as a five-day continuous infusion modulated by short infusions of 100 mg/m2 folinic acid twice daily. The dose-limiting toxicities were hand-foot syndrome and severe mucositis. A response rate of 21% and 50% stable disease could be achieved. In order to determine the effectiveness and tolerability, we initiated a multicenter phase II trial applying a 650 mg/m2 recommended dose of 5-FU and 100 mg/m2 folinic acid twice daily every three weeks. Patients and methods From January 1994 to July 1996, 88 advanced and progressive colorectal cancer patients either previously treated with a bolus schedule of 5-FU and folinic acid (34 patients) or without (54 patients) previous chemotherapy were included in this trial. Results In the group of previously treated patients, therapy led to 6% (2 of 34 patients) remissions while stable disease could be observed in 68% (23 of 34 patients) of the patients. The median survival time was 14 months. The main toxicity was mucositis grade 3 in 15% of the previously treated patients and 10% in the nonpretreated patients. In the population of nonpretreated patients, the overall response rate was 15% (eight of 54 patients) and stable disease could be induced in 67% (36 of 54 patients). The median survival time was 13.7 months. Conclusions This regimen is an active second-line therapy in advanced colorectal cancer with minimal toxicity, thus preserving the quality of life during palliative chemotherapy. Antiturnor activity in previously untreated patients does not seem superior to that obtained with weekly regimens applying 24- or 48-hour continuous infusions of 5-FU and folinic acid.