The Spanish experience with high-dose infusional 5-fluorouracil (5-FU) in colorectal cancer. The Spanish Cooperative Group For Gastrointestinal Tumor Therapy (TTD).
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.
Aranda
E
E
Hospital Clínico Provincial, Córdoba.
Cervantes
A
A
Carrato
A
A
Antón-Torres
A
A
Massutí
T
T
Fernández-Martos
C
C
Díaz-Rubio
E
E
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced / Q000150:complications; D000931:Antidotes / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D003967:Diarrhea / Q000139:chemically induced / Q000150:complications; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007970:Leukopenia / Q000139:chemically induced / Q000150:complications; D008297:Male; D008875:Middle Aged; D013030:Spain; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000150:complications
D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil