Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial.
OBJECTIVE
This randomized, 2 x 2 factorial study compared a semimonthly (LVFU2) with a monthly (FULV) regimen of fluorouracil and leucovorin and 24 versus 36 weeks of each regimen as adjuvant treatment of patients with stage II (Dukes' B2) and III (Dukes' C) colon cancer.


METHODS
LVFU2 was administered semi-monthly for 2 consecutive days as dl- or l-leucovorin (200 or 100 mg/m2, respectively) as a 2-hour infusion, followed by a 400 mg/m2 FU bolus and 600 mg/m2 of FU as a 22-hour continuous infusion. FULV was administered monthly for 5 consecutive days as a 15-minute infusion of dl- or l-leucovorin, followed by 400 mg/m2 of FU as a 15-minute infusion.


RESULTS
A total of 905 patients were randomly assigned. The median follow-up was 41 months. Disease-free survival was similar between the LVFU2 and FULV groups (127 v 124 events; hazard ratio [HR] = 1.04; P =.74) and between 24 and 36 weeks of therapy (128 v 123 events; HR = 0.94; P =.63). Analysis of overall survival showed a slight excess in the number of deaths in LVFU2 compared with FULV (73 v 59), but this difference was not statistically significant (HR = 1.26; 95% confidence interval, 0.90 to 1.78; P =.18). The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhea, and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, P <.001).


CONCLUSIONS
Our data confirm that LVFU2 is less toxic than FULV. At a median follow-up of 41 months, no statistically significant difference could be detected in disease-free or overall survival between the treatment groups or treatment durations.
Andre
Thierry
T
Hôpital Tenon, Groupe d'Etude et de Recherche Clinique en Oncologie Radioitherapie, Paris. thierry.andre@tnn.ap-hop-paris.fr.
Colin
Philippe
P
Louvet
Christophe
C
Gamelin
Erik
E
Bouche
Olivier
O
Achille
Emmanuel
E
Colbert
Nicolas
N
Boaziz
Catherine
C
Piedbois
Pascal
P
Tubiana-Mathieu
Nicole
N
Boutan-Laroze
Arnaud
A
Flesch
Michel
M
Buyse
Marc
M
de Gramont
Aimery
A
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome
D002955:Leucovorin; D005472:Fluorouracil