Five-day continuous infusion of 5-fluorouracil and pulsed folinic acid in patients with metastatic colorectal carcinoma: an effective second-line regimen.
OBJECTIVE
A previous phase I trial in 14 pretreated patients with progressive advanced colorectal cancer demonstrated 750 mg/m2 to be the maximum tolerable dose of 5-fluorouracil (5-FU) administered as a five-day continuous infusion modulated by short infusions of 100 mg/m2 folinic acid twice daily. The dose-limiting toxicities were hand-foot syndrome and severe mucositis. A response rate of 21% and 50% stable disease could be achieved. In order to determine the effectiveness and tolerability, we initiated a multicenter phase II trial applying a 650 mg/m2 recommended dose of 5-FU and 100 mg/m2 folinic acid twice daily every three weeks.


METHODS
From January 1994 to July 1996, 88 advanced and progressive colorectal cancer patients either previously treated with a bolus schedule of 5-FU and folinic acid (34 patients) or without (54 patients) previous chemotherapy were included in this trial.


RESULTS
In the group of previously treated patients, therapy led to 6% (2 of 34 patients) remissions while stable disease could be observed in 68% (23 of 34 patients) of the patients. The median survival time was 14 months. The main toxicity was mucositis grade 3 in 15% of the previously treated patients and 10% in the nonpretreated patients. In the population of nonpretreated patients, the overall response rate was 15% (eight of 54 patients) and stable disease could be induced in 67% (36 of 54 patients). The median survival time was 13.7 months.


CONCLUSIONS
This regimen is an active second-line therapy in advanced colorectal cancer with minimal toxicity, thus preserving the quality of life during palliative chemotherapy. Antitumor activity in previously untreated patients does not seem superior to that obtained with weekly regimens applying 24- or 48-hour continuous infusions of 5-FU and folinic acid.
Streit
M
M
Department of Hematology and Oncology, University Hospital Benjamin Franklin, Free University of Berlin, Germany.
Jaehde
U
U
Stremetzne
S
S
Ridwelski
K
K
Kerz
H
H
Strohbach
F
F
Hohenberger
P
P
Zwiebel
F M
FM
Hebart
H
H
Böthig
R
R
Kairies
M
M
Zillig
D
D
Schuchmann
S
S
Warnecke
S
S
Thiel
E
E
Kreuser
E D
ED
D000328:Adult; D000368:Aged; D000931:Antidotes / Q000008:administration & dosage*; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000556:secondary; D008175:Lung Neoplasms / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D000931:Antidotes; D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil