A simplified regimen of weekly high dose 5-fluorouracil and leucovorin as a 24-hour infusion in patients with advanced colorectal carcinoma.
BACKGROUND
Reports of in vitro experiments in colorectal carcinoma cells suggest that prolonged cellular exposure to 5-fluorouracil (5-FU) combined with relatively low concentrations of leucovorin (LV) provides optimal enhancement of 5-FU efficacy. In this study, a simplified regimen of weekly 24-hour infusion of high dose 5-FU combined with a relatively low dose of LV was used to treat patients with advanced colorectal carcinoma.


METHODS
Thirty-six patients with advanced colorectal carcinoma received 5-FU, 2600 mg/m2, admixed with LV, 100 mg/m2, in a portable infusion pump administered intravenously over a 24-hour period. High dose 5-FU/LV was delivered once a week for 5 consecutive weeks followed by a 1-week recovery period. All patients were assessable for toxicity and response.


RESULTS
Two complete responses and 15 partial responses were observed (response rate of 47.2%; 95% confidence interval, 30.1-64.4%). The median response duration was 9.6 months. The median survival and time to progression were 11.9 months and 7.1 months, respectively. The toxicity was mild and acceptable. The major dose-limiting factors were hand-foot syndrome and fatigue.


CONCLUSIONS
This simplified regimen of weekly 24-hour continuous infusion of high dose 5-FU/LV is an effective regimen in the treatment of patients with advanced colorectal carcinoma. Further study of the pharmacokinetics of combination therapy with 5-FU and LV as used in this regimen and its correlation with response and toxicity is warranted.
Yang
T S
TS
Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan.
Hsu
K C
KC
Chiang
J M
JM
Tang
R
R
Chen
J S
JS
Changchien
C R
CR
Wang
J Y
JY
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D002955:Leucovorin; D005472:Fluorouracil