The Spanish experience with high-dose infusional 5-fluorouracil (5-FU) in colorectal cancer. The Spanish Cooperative Group For Gastrointestinal Tumor Therapy (TTD)

• Published in: The Journal of infusional chemotherapy Vol. 6; no. 3; p. 118
• Main Authors: Aranda, E, Cervantes, A, Carrato, A, Antón-Torres, A, Massutí, T, Fernández-Martos, C, Díaz-Rubio, E
• Format: Journal Article
• Language: English
• Published: United States 1996
• Subjects: Administration, Oral; Adult; Aged; Anemia - chemically induced; Anemia - complications; Antidotes - therapeutic use; Antimetabolites, Antineoplastic - administration & dosage; Antimetabolites, Antineoplastic - adverse effects; Antimetabolites, Antineoplastic - therapeutic use; Carcinoma - drug therapy; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Diarrhea - chemically induced; Diarrhea - complications; Dose-Response Relationship, Drug; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Humans; Infusions, Intravenous; Leucovorin - administration & dosage; Leucovorin - adverse effects; Leucovorin - therapeutic use; Leukopenia - chemically induced; Leukopenia - complications; Male; Middle Aged; Spain; Treatment Outcome; Vomiting - chemically induced; Vomiting - complications; Spain
• ISSN: 1060-0051

Background In a previous phase I to II trial, we have shown that the maximum tolerable dose (MTD) of 5-Fluorouracil (5-FU) in 48-hour continuous infusion (CI) weekly was 3.5 gr/m2. In a subsequent confirmative phase II trial with 85 evaluable patients, a 38.5% response rate was obtained and the median survival reached was 12 months. These data were comparable to those achieved by biochemical modulation of 5-FU with Leucovorin. On this basis we tried to modulate high-dose 5-FU (3 gr/m2) with oral leucovorin (LV) but the regimen was 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 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. Overall response rate was 37.5% (95% CI, 28% to 46.8%). Median time to progression has been 7.4 months, and median survival 14.4 months. WHO grade 3 diarrhea was seen in 27 patients (24.5%). Grade 3 mucositis was also seen in 9 (8.1%) patients, and grade 4 was observed in one. Grade 3 nausea and vomiting was reported in 13 (11.7%) patients. Grade 3 hand-foot syndrome was detected in only 5 (4.5%) patients. Grade 4 leukopenia was observed in 1 case and grade 3 to 4 thrombocytopenia was observed in two cases, respectively. 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 main limiting toxicities. 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.