Phase III trial of irinotecan plus infusional 5-fluorouracil/folinic acid versus irinotecan plus oxaliplatin as first-line treatment of advanced colorectal cancer.
OBJECTIVE
To determine whether irinotecan plus oxaliplatin (mIROX) is superior to irinotecan plus infusional 5-fluorouracil, leucovorin (FUFIRI) as first-line therapy of patients with metastatic colorectal cancer (mCRC).


METHODS
A phase III, randomised, open-label multicentre study compared standard treatment with FUFIRI (irinotecan 80 mg/m(2), 5-fluorouracil 2000 mg/m(2), folinic acid 500 mg/m(2) weekly times 6) to mIROX using an identical schedule of irinotecan plus oxaliplatin 85 mg/m(2) applied on days 1, 15 and 29 of a 7-week cycle. The primary end-point was progression-free survival (PFS).


RESULTS
A total of 479 eligible patients were randomly assigned. Progression-free survival was 7.2 months in the mIROX arm and 8.2 months in the FUFIRI arm [hazard ratio=1.14; 95% confidence interval (CI) 0.94-1.37; P=0.178]. Comparable results were also obtained for overall survival time with 19 months in the mIROX-arm and 22 months in the FUFIRI-arm (hazard ratio=1.08, P=0.276). Both regimens induced an identical objective response rate (ORR) of 41%, but disease control rate (ORR plus stable disease) was significantly greater in the FUFIRI group (81% versus 68%, P=0.001). Most frequent grades 1-4 side-effects of mIROX and FUFIRI treatment were nausea (80% versus 73%) and delayed diarrhoea (79% versus 68%). Grades 3-4 toxicities were generally below 10%, except for diarrhoea which was more frequent in the mIROX-arm compared to the FUFIRI-arm (19% versus 30%, P=0.006)


CONCLUSIONS
mIROX failed to show superior activity compared to high-dose 5-FU/folinic acid plus irinotecan. Due to better tolerability the combination of high-dose 5-FU/folinic acid and irinotecan remains a standard of care in first-line treatment of metastatic colorectal cancer.
Klinikum Sankt Marien, Amberg, Germany.
Ludwig
L
Fischer von Weikersthal
Andreas
A
Schalhorn
Martina
M
Stauch
Detlef
D
Quietzsch
Peter A
PA
Maubach
Helmut
H
Lambertz
Daniel
D
Oruzio
Rudolf
R
Schlag
Karin
K
Weigang-Köhler
Ute
U
Vehling-Kaiser
Manfred
M
Schulze
Juergen
J
Truckenbrodt
Mariele
M
Goebeler
Johann
J
Mittermüller
Daniel
D
Bosse
Borika
B
Szukics
Marc
M
Grundeis
Thomas
T
Zwingers
Clemens
C
Giessen
Volker
V
Heinemann
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D055815:Young Adult
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin