Survival impact of chemotherapy in patients with colorectal metastases confined to the liver: a re-analysis of 1458 non-operable patients randomised in 22 trials and 4 meta-analyses. Meta-Analysis Group in Cancer.
BACKGROUND
Metastases confined to the liver is a frequent situation in patients with advanced colorectal cancer. For non-operable patients, 5-FU-based chemotherapy is often proposed but the importance of the choice of first line 5-FU regimen remains debatable.


METHODS
In four previously performed meta-analyses, our group had compared bolus intravenous fluoropyrimidines (bolus FU group) with experimental fluoropyrimidines (experimental FU group), consisting of 5-FU plus leucovorin, 5-FU plus methotrexate, continuous infusion 5-FU, or hepaticartery infusion FUDR. We re-analysed this data set to focus on 1458 patients with non-operable colorectal metastases confined to the liver, randomised in 22 trials. All analyses were stratified by trial and used individual patient data.


RESULTS
Median survival times were 11.3 months in the bolus FU group (95% CI: 10.5-12.0 months) compared to 12.7 months in the experimental FU group (95% CI: 120-13.1 months). This difference, although clinically small, was statistically significant, with an overall survival hazard ratio of 0.88 (95% CI: 0.79-0.99, P = 0.037). In a multivariate analysis, performance status was the only significant predictor of survival (P < 10(-4)), whereas the statistical significance of allocated treatment was borderline (P = 0.058).


CONCLUSIONS
The outcome of patient with non-operable colorectal metastases confined to the liver is poor, and mainly driven by their initial performance status. Experimental chemotherapy schedules yield a small improvement in their overall survival, indicating the importance of the choice of first-line chemotherapy.
Thirion
P
P
Department of Oncology, Henri Mondor Hospital, Créteil, France.
Wolmark
N
N
Haddad
E
E
Buyse
M
M
Piedbois
P
P
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D005069:Evaluation Studies as Topic; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D015552:Injections, Intralesional; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D010166:Palliative Care / Q000379:methods*; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D019452:Terminally Ill; D016896:Treatment Outcome
D005467:Floxuridine; D005472:Fluorouracil; D008727:Methotrexate