Outpatient weekly high-dose continuous-infusion 5-fluorouracil plus oral leucovorin in advanced colorectal cancer. A phase II trial

• Published in: Annals of oncology Vol. 7; no. 6; pp. 581 - 585
• Main Authors: Aranda, E., Cervantes, A., Carrato, A., Fern´ndez-Martos, C., Antón-Torres, A., Massutí, T., Barneto, I., García-Conde, J., Barón, J. M, Díaz-Rubio, E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.1996
• 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; Rectal disease; Intravenous administration; Toxicity; Oral administration; Malignant tumor; Colonic disease; Chemotherapy; Treatment; Phase II trial; Rectum; Digestive diseases; Intestinal disease; Pyrimidine derivatives; Advanced stage; Colon; Fluorine Organic compounds; High dose
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/oxfordjournals.annonc.a010674

Background: Background: In a previous phase I–II trial we showed that maximum tolerable dose (MTD) of 5-fluorouracil (5-FU) a weekly 48-hour continuous infusion (CI) was 3.5 g/m2. In a subsequent confirmative phase II trial with 85 evaluable patients, a 38.5% response rate was obtained, and a median survival of 12 months. These data were comparable to those achieved by biochemical modulation of 5-FU with leucovorin. On this basis we attempted to modulate high-dose 5-FU (3 g/m2) with oral leucovorin (LV) but the regimen too toxic and the dose had to be reduced. A new phase II trial with 2 g/m2/week plus oral leucovorin was planned. Patients and methods: From July 1992 to June 1994, 110 previously untreated patients with advanced, measurable colorectal cancer were included in a multicenter study. The patients received, on an outpatient basis, 5-FU 2 g/m2 by continuous infusion for 48 hours once a week until progression or the appearance of toxic effects. Oral leucovorin (60 mg every six hours) was also given during the 5-FU infusion. Results: Patients received a median dose intensity of 5-FU of 1.6 g/m2/week (range 0.9–2). Three complete responses and 36 partial responses were observed. The overall response rate was 37.5% (95% CI, 28% to 46.8%), the median time to progression 7.4 months and median survival 14.5 months. W.H.O. grade 3 diarrhea occurred in 27 patients (24.5%); grade 3 mucositis was observed in 9 (8.1%) patients and grade 4 in one. Grade 3 nausea and vomiting was reported in 13 (11.7%) patients, while grade 3 hand-foot syndrome was detected in only 5 (4.5%). Grade 4 leukopenia occurred in one patient and grade 3–4 thrombocytopenia in two. Conclusion: Oral leucovorin modulation of weekly 48-hour continuous infusion of 5-FU at 2 g/m2 is an active regimen, with diarrhea and mucositis as the main limiting toxic effects. Its antitumor activity does not seem superior to that obtained with a weekly 48-hour continuous infusion of 5-FU alone at a dose of 3.5 g/m2.