A phase II trial of weekly high dose continuous infusion 5‐fluorouracil plus oral leucovorin in patients with advanced colorectal cancer

• Published in: Cancer Vol. 76; no. 4; pp. 559 - 563
• Main Authors: Aranda, Enrique, Cervantes, Andrés, Dorta, Javier, Blanco, Esperanza, Fernández‐Martos, Carlos, Cruz‐Hernandez, Juan José, Carrato, Alfredo, Gonzalez‐Mancha, Rosario, García‐Conde, Javier, Díaz‐Rubio, Eduardo
• Format: Journal Article
• Language: English
• Published: New York Wiley Subscription Services, Inc., A Wiley Company 15.08.1995; Wiley-Liss
• Subjects: advanced colorectal cancer; Antineoplastic agents; biochemical modulation; Biological and medical sciences; Chemotherapy; continuous infusion; fluorouracil; Medical sciences; Pharmacology. Drug treatments; Phase II trial; Antineoplastic agent; Human; Drug combination; Intravenous administration; Toxicity; Oral administration; Administration schedule; Malignant tumor; Result; Chemotherapy; Treatment; Phase II trial; Rectum; Digestive diseases; Intestinal disease; Pyrimidine derivatives; Advanced stage; Colon; Fluorine Organic compounds; High dose; Anorectal disease
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/1097-0142(19950815)76:4<559::AID-CNCR2820760404>3.0.CO;2-O

Background. In a previous Phase II trial, the authors showed that a weekly continuous infusion of 5‐fluorouracil (5‐FU) at a dose of 3.5 g/m2 for 48 hours is an active treatment for advanced colorectal cancer. The overall response rate was 38.5%, and the median survival was 12 months. These data were comparable to those achieved by biochemical modulation of 5‐FU with leucovorin. To study the modulation of this weekly, high dose, continuous infusion 5‐FU with oral leucovorin, a new Phase II trial was planned. Methods. From December 1991 to July 1992, 43 previously untreated patients with measurable advanced colorectal cancer were included in a multicenter study. They received on an outpatient basis 5‐FU at a weekly dose of 3 g/m2 by continuous infusion for 48 hours until progression or toxicity. Oral leucovorin (60 mg every 6 hours) also was given during the infusion of 5‐FU. Results. Patients received a median dose intensity of 5‐FU of 2.2 g/m2/week (range, 0.76‐3 g/m2/week). One complete response and 11 partial responses were observed. The overall response rate was 29% (95% confidence interval [CI], 16–45%). Median time to progression was 7 months, and the median survival was 15 months. World Health Organization Grades 3 and 4 diarrhea were observed in 19 (45%) and 6 (14%) patients, respectively. Grade 3 mucositis also was observed in 10 (24%) patients, and Grade 4 mucositis was observed in 1. Grade 3 nausea and vomiting were reported in seven (17%) patients. Grade 3 hand–foot syndrome was detected in only two (2.5%) patients. No leukopenia or thrombocytopenia was observed. Conclusions. Oral leucovorin modulation of a weekly 48‐hour infusion of 5‐FU at a dose of 3 g/m2 of leucovorin is a toxic regimen, always requiring dose reduction, with diarrhea and mucositis as the main limiting toxicities. Its antitumor activity does not seem superior to that observed with a weekly 48‐hour infusion of 5‐FU alone at a dose of 3.5 g/m2. Cancer 1995; 76:559–63.