Activity of high dose 24 hour 5-fluorouracil infusion plus L-leucovorin in advanced colorectal cancer.
BACKGROUND
Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken.


METHODS
Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines.


RESULTS
The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively.


CONCLUSIONS
L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.
Nobile
M T
MT
Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Barzacch
M C
MC
Sanguineti
O
O
Chiara
S
S
Gozza
A
A
Vincenti
M
M
Lavarello
A
A
Cognein
P
P
Lionetto
R
R
Percivale
P L
PL
Bertoglio
S
S
Murolo
C
C
Esposito
M
M
Vannozzi
M O
MO
Rosso
R
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D002955:Leucovorin; D005472:Fluorouracil