Predictive factors for the benefit of perioperative FOLFOX for resectable liver metastasis in colorectal cancer patients (EORTC Intergroup Trial 40983).
OBJECTIVE
In EORTC study 40983, perioperative FOLFOX increased progression-free survival (PFS) compared with surgery alone for patients with initially 1 to 4 resectable liver metastases from colorectal cancer (CRC). We conducted an exploratory retrospective analysis to identify baseline factors possibly predictive for a benefit of perioperative FOLFOX on PFS.


METHODS
The analysis was based on 237 events from 342 eligible patients. Cox proportional hazards regression models with a significance level of 0.1 were used to build up univariate and multivariate models.


RESULTS
After adjustment for identified prognostic factors, moderately (5.1-30 ng/mL) and highly (>30 ng/mL) elevated carcinoembryonic antigen (CEA) serum levels were both predictive for the benefit of perioperative chemotherapy (interaction P = 0.07; hazard ratio [HR] = 0.58 and HR = 0.52 for treatment benefit). For patients with moderately or highly elevated CEA (>5 ng/mL), the 3-year PFS was 35% with perioperative chemotherapy compared to 20% with surgery alone. Performance status (PS) 0 and BMI lower than 30 were also predictive for the benefit of perioperative chemotherapy (interaction P = 0.04 and P = 0.02). However, the number of patients with PS 1 and BMI 30 or higher were limited. The benefit of perioperative therapy was not influenced by the number of metastatic lesions (1 vs 2-4, interaction HR = 0.98).


CONCLUSIONS
Perioperative FOLFOX seems to benefit in particular patients with resectable liver metastases from CRC when CEA is elevated and when PS is unaffected, regardless of the number of metastatic lesions.ClinicalTrials.gov number NCT00006479.
Haukeland University Hospital, Bergen, Norway. Halfdan.sorbye@helse-bergen.no
Halfdan
H
Sorbye
Murielle
M
Mauer
Thomas
T
Gruenberger
Bengt
B
Glimelius
Graeme J
GJ
Poston
Peter M
PM
Schlag
Philippe
P
Rougier
Wolf O
WO
Bechstein
John N
JN
Primrose
Euan T
ET
Walpole
Meg
M
Finch-Jones
Daniel
D
Jaeck
Darius
D
Mirza
Rowan W
RW
Parks
Laurence
L
Collette
Eric
E
Van Cutsem
Werner
W
Scheithauer
Manfred P
MP
Lutz
Bernard
B
Nordlinger
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D019990:Perioperative Care; D011379:Prognosis; D012189:Retrospective Studies
D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil