Modification of 5-fluorouracil activity by high-dose methotrexate or leucovorin in advanced colorectal carcinoma.
21 patients with advanced colorectal carcinoma were entered into a phase II study to evaluate efficacy and toxicity of methotrexate (MTX), 1500 mg/m2 rapid infusion on day 1, combined with continuous infusion of 5-fluorouracil (5-FU), 600 mg/m2 per 24 h on days 1-4. 12 patients who had progressive disease during this regimen subsequently received high-dose leucovorin, 200 mg/m2 bolus injection on days 1-4, combined with 4 days' continuous infusion of 5-FU. In the MTX/5-FU group 1 pathologically proven complete remission and 3 partial remissions were seen (response rate 20%). The median progression-free interval was 30 weeks. In 12 patients with progressive disease leucovorin/5-FU stabilized disease in 2 (17%). Toxicity in both regimens was tolerable, gastro-intestinal side-effects being most frequent. There were no treatment-related deaths. Median survival time was 10 months. Serum levels of carcinoembryonic antigen before treatment or doubling-time during progression did not correlate with survival.
Sinnige
H A
HA
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
Sleijfer
D T
DT
de Vries
E G
EG
Willemse
P H
PH
Mulder
N H
NH
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002272:Carcinoembryonic Antigen / Q000032:analysis; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D004341:Drug Evaluation; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011379:Prognosis
D002272:Carcinoembryonic Antigen; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate