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.
Department of Medical Oncology, Royal Prince Alfred Hospital Sydney Cancer Centre, Sydney, Australia. sclarke@med.usyd.edu.au
Stephen
S
Clarke
David
D
Goldstein
Paul
P
Mitchell
Michael
M
Michael
Philip
P
Beale
Michael
M
Friedlander
John
J
Zalcberg
Shane
S
White
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