A randomized phase II trial evaluating safety and efficacy of an experimental chemotherapy regimen (irinotecan + oxaliplatin, IRINOX) and two standard arms (LV5 FU2 + irinotecan or LV5 FU2 + oxaliplatin) in first-line metastatic colorectal cancer: a study of the Digestive Group of the Fédération Nationale des Centres de Lutte Contre le Cancer.
BACKGROUND
To assess activity and safety of an experimental combination of irinotecan and oxaliplatin (IRINOX) as first-line treatment in advanced colorectal cancer.


METHODS
In this randomized phase II trial, 80 patients were treated: arm A (IRINOX) in 40 patients received at day 1 oxaliplatin 85 mg/m(2) and irinotecan 180 mg/m(2) biweekly, standard arm B received a biweekly simplified folinic acid (FA) and fluorouracil (FU), FA 200 mg/m(2) in a 2-h infusion and bolus injection of 5FU 400 mg/m(2) on day 1, then a two 400 mg/m(2) continuous infusion of FU on days 1 and 2 with either oxaliplatin 85 mg/m(2) (20 patients) or irinotecan 180 mg/m(2) (20 patients).


RESULTS
Twenty-one partial responses (52.5%, median duration 7.2 months) were observed with the IRINOX arm and two complete and 20 partial responses (55%, median duration 6.4 months) with arm B. Median progression-free and overall survival times were 8.4 and 19 months, respectively, in the IRINOX arm and 8.1 and 20.4 months in arm B. Main grade 3/4 toxic effects were, respectively, neutropenia 42.5% and 32.5%; febrile neutropenia 10% and 5%; diarrhea 32.5% and 7.5%; vomiting 10.0% and 5%; neurosensory toxicity 17.5% and 7.5%.


CONCLUSIONS
The IRINOX arm has a manageable toxicity and is active.
Bécouarn
Y
Y
Department of Digestive Oncology, Institut Bergonié, Regional Cancer Center, Bordeaux, France. becouarn@bergonie.org
Senesse
P
P
Thézenas
S
S
Boucher
E
E
Adenis
A
A
Cany
L
L
Jacob
J H
JH
Cvitkovic
F
F
Montoto-Grillot
C
C
Ychou
M
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin