Comparison of the levogyre and dextro-levogyre forms of leucovorin in a phase III trial of bimonthly LV5FU2 versus monthly 5-fluorouracil and high-dose leucovorin for patients with stage II and III colon cancer (GERCOR C96.1).
BACKGROUND
These analyses compare the safety and efficacy of 2 forms (levogyre [L] and dextro-levogyre [DL]) of leucovorin (LV) when used with 5-fluorouracil (5-FU) for the adjuvant treatment of patients with stage II and III colon cancer.


METHODS
The analysis used primary efficacy and safety data of a phase III trial comparing monthly 5-FU/LV or bimonthly LV5FU2 (LV 200 mg/m2 intravenously over 2 hours followed by 5-FU 400 mg/m2 bolus and then 600 mg/m2 continuous intravenous infusion over 22 hours, days 1 and 2, every 2 weeks). In both regimens, depending on the choice made by each center, patients received either DL-LV (200 mg/m2) or L-LV (100 mg/m2).


RESULTS
L-LV and DL-LV were administered respectively to 60% (n = 519) and 40% (n = 357) of the patients. Important prognostic characteristics were well balanced between the 2 groups. The proportion of any grade 3/4 toxicity was 20% in the L-LV group and 17% in the DL-LV group. There was no statistical difference in terms of toxicity between the 2 groups. The median follow-up time was 6.1 years. There were no statistically significant differences between L-LV and DL-LV in terms of either disease-free survival (66.7% vs. 67.2%; hazard ratio [HR], 1.03; 95% CI, 0.82-1.31; P = .78) or overall survival (78.2% vs. 74.5%; HR, 1.28; 95% CI, 0.97-1.69; P = .078).


CONCLUSIONS
This study supports the use of either DL (200 mg/m2) or L (100 mg/m2) LV in association with 5-FU as adjuvant treatment of patients with colon cancer.
Baumgaertner
Isabelle
I
Department of Hepatogastroenterology, Hôpital Pitié-Salpétrière, Paris, France.
Quinaux
Emmanuel
E
Khalil
Ahmed
A
Louvet
Christophe
C
Buyse
Marc
M
de Gramont
Aimery
A
André
Thierry
T
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016001:Confidence Intervals; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000009:adverse effects / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D014803:Vitamin B Complex; D002955:Leucovorin; D005472:Fluorouracil