Lack of effectiveness of combined 5-fluorouracil and leucovorin in patients with 5-fluorouracil-resistant advanced colorectal cancer.
Favorable results have been reported for the treatment of advanced colorectal cancer with the combination of 5-fluorouracil (5-FU) and leucovorin (LV). In these investigations the highest response rates were obtained in non-pretreated patients. In the present study, 22 patients with primary or acquired resistance to single-agent 5-FU and documented progressive disease on 5-FU were given a bolus injection of LV at a dose of 200 mg/m2, 1 h prior to a 2 h infusion of 5-FU at a dose of 370-770 mg/m2 on 5 consecutive days, and this was repeated every 3 weeks. Whenever possible the dose of 5-FU was escalated to find the maximum tolerable dose. No objective response was observed. Five patients had short-lasting stable disease. Despite 5-FU dose escalation, toxicity was acceptable. One patient developed 5-FU-related angina pectoris with EKG changes. It is concluded that in the schedule used, combined LV/5-FU treatment is ineffective for patients with 5-FU-resistant advanced colorectal cancer.
van Groeningen
C J
CJ
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
Peters
G J
GJ
Pinedo
H M
HM
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004351:Drug Resistance; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged
D002955:Leucovorin; D005472:Fluorouracil