Doxifluridine and leucovorin: an oral treatment combination in advanced colorectal cancer.
OBJECTIVE
This study was designed to test the activity and feasibility of an all-oral regimen of levo-leucovorin and doxifluridine (dFUR) in the treatment of advanced colorectal cancer and to establish whether the pharmacokinetics of dFUR and fluorouracil (FU) are affected by demographic and/or biologic parameters.


METHODS
One hundred eight patients with histologically proven colorectal cancer received orally administered levo-leucovorin 25 mg followed 2 hours later by dFUR 1,200 mg/m2 on days 1 to 5, with the cycle being repeated every 10 days.


RESULTS
Among 62 previously untreated patients, two complete responses (CRs) and 18 partial responses (PRs) were observed (overall response rate, 32%; 95% confidence interval, 21% to 45%). The median response duration was 4 months (range, 2 to 13) and the median survival time, 14 months. Among 46 pretreated patients, there were three CRs and three PRs (response rate, 13%; 95% confidence interval, 5% to 26%). In this group of patients, the median response duration was 4 months (range, 1 to 12) and the median survival time, 12 months. No toxic deaths were observed. The only World Health Organization (WHO) grade 3 to 4 side effect was diarrhea (32 patients).


CONCLUSIONS
This regimen is active in previously untreated colorectal cancer patients and combines good compliance with safety. Limited but definite efficacy was also detected in the patients previously treated with FU, which suggests incomplete cross-resistance between the two drugs. The pharmacokinetic results suggest that the conversion rate of dFUR to FU increases between days 1 and 5, but that FU levels remain low in comparison to those measured after classical FU therapy. Under the experimental conditions used in this study, the interpatient variability of pharmacokinetic parameters remains largely unexplained by the tested variables.
Bajetta
E
E
Division of Medical Oncology B, Instituto Nazionale per lo Studio e la Cura dei Tumori, Italy.
Colleoni
M
M
Di Bartolomeo
M
M
Buzzoni
R
R
Bozzetti
F
F
Doci
R
R
Somma
L
L
Cappuzzo
F
F
Stampino
C G
CG
Guenzi
A
A
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D005467:Floxuridine; D002955:Leucovorin; C025034:doxifluridine