Modification of leucovorin dose within a simplified FOLFOX regimen improves tolerability without compromising efficacy.
BACKGROUND
This analysis assesses the efficacy and safety of a modified FOLFOX (oxaliplatin/leucovorin [LV]/5-fluorouracil [5-FU]) regimen given with a low dose of LV.


METHODS
Forty patients with previously untreated metastatic colorectal cancer were enrolled to receive every-2-week cycles of oxaliplatin 100 mg/m(2) intravenously administered over 2 hours concurrently with LV 20 mg/m(2) bolus and 5-FU 400 mg/m(2) bolus, followed by a 46-hour infusion of 5-FU 2.4 g/m(2).


RESULTS
Thirty-nine patients received > or = 1 oxaliplatin dose and a median of 10 treatment cycles (range, 1-13 cycles). Thirteen patients (34%) experienced grade 3/4 neutropenia, whereas 21% of patients experienced grade 3 neurotoxicity. Of 37 eligible patients, complete or partial responses were observed in 18 patients (49% [95% confidence interval (CI), 32%-66%]). The median progression-free survival was 6.2 months (95% CI, 5.5-8.7 months) with a median overall survival of 14.2 months (95% CI, 10-20.5 months).


CONCLUSIONS
A modified schedule of FOLFOX using a lower than standard dose of LV provides good response and survival results with excellent safety. A comparison with a previous study undertaken in the same centers using identical inclusion/exclusion criteria but using higher doses of LV suggests that reducing the dose of LV improves safety without compromising efficacy.
Clarke
Stephen
S
Department of Medical Oncology, Royal Prince Alfred Hospital Sydney Cancer Centre, Sydney, Australia. sclarke@med.usyd.edu.au
Goldstein
David
D
Mitchell
Paul
P
Michael
Michael
M
Beale
Philip
P
Friedlander
Michael
M
Zalcberg
John
J
White
Shane
S
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008297:Male; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D015996:Survival Rate
D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil