Tritherapy with fluorouracil/leucovorin, irinotecan and oxaliplatin (FOLFIRINOX): a phase II study in colorectal cancer patients with non-resectable liver metastases.
OBJECTIVE
To assess the rate of R(0) resection of liver metastases achieved after chemotherapy with FOLFIRINOX.


METHODS
Patients with histologically proven primary colorectal cancer and bidimensionally measurable liver metastasis, not fully resectable based on technical inability to achieve R(0) resection, but potentially resectable after tumor reduction, were given FOLFIRINOX: oxaliplatin 85 mg/m(2), irinotecan 180 mg/m(2), leucovorin 400 mg/m(2), bolus fluorouracil 400 mg/m(2) and fluorouracil 46-h continuous IV infusion 2,400 mg/m(2), every 2 weeks for a maximum of 12 cycles.


RESULTS
Thirty-four patients were enrolled. Response rate before surgery was 70.6% (95%CI: 52.5-84.9). Twenty-eight patients (82.4%) underwent hepatic resection and nine achieved R(0) resection [26.5% (95% CI: 12.9-44.4%)]. The rate of clinical complete remission after surgery was 79.4%. Two-year overall survival was 83%. The most frequent grade 3 or 4 toxicities were neutropenia (64.8%), diarrhea (29.4%), fatigue (23.5%), abdominal cramps (14.7%), neuropathy and nausea (11.8% each), and AST/ALT elevation (14.7/11.8%). Only one patient experienced febrile neutropenia, four patients withdrew due to toxicity and no toxic death was observed.


CONCLUSIONS
FOLFIRINOX, with an acceptable toxicity profile, shows a high response rate in liver metastases from colorectal cancer. The rate of hepatic resection in patients initially not resectable, is attractive and warrants further assessment of this regimen in randomized studies compared to standard regimens.
Ychou
M
M
Centre Régional de Lutte contre le Cancer Val d'Aurelle, 208 rue des apothicaires, 34298, Montpellier cedex 05, France. marc.ychou@valdorel.fnclcc.fr
Viret
F
F
Kramar
A
A
Desseigne
F
F
Mitry
E
E
Guimbaud
R
R
Delpero
J R
JR
Rivoire
M
M
Quénet
F
F
Portier
G
G
Nordlinger
B
B
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000556:secondary / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000077150:Oxaliplatin
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin