Intrahepatic arterial versus intravenous fluorouracil and folinic acid for colorectal cancer liver metastases: a multicentre randomised trial.
BACKGROUND
The liver is the most frequent site for metastases of colorectal cancer, which is the second largest contributor to cancer deaths in Europe. We did a randomised trial to compare an intrahepatic arterial (IHA) fluorouracil and folinic acid regimen with the standard intravenous de Gramont fluorouracil and folinic acid regimen for patients with adenocarcinoma of the colon or rectum, with metastases confined to the liver.


METHODS
We randomly allocated 290 patients from 16 centres to receive either intravenous chemotherapy (folinic acid 200 mg/m2, fluorouracil bolus 400 mg2 and 22-h infusion 600 mg/m2, day 1 and 2, repeated every 14 days), or IHA chemotherapy designed to be equitoxic (folinic acid 200 mg/m2, fluorouracil 400 mg/m2 over 15 mins and 22-h infusion 1600 mg/m2, day 1 and 2, repeated every 14 days). The primary endpoint was overall survival, and analysis was by intention to treat.


RESULTS
50 (37%) patients allocated to IHA did not start their treatment, and another 39 (29%) had to stop before receiving six cycles of treatment because of catheter failure. The IHA group received a median of two cycles (0-6), compared with 8.5 (6-12) for the intravenous group. 45 (51%) IHA patients who did not start or did not receive six cycles switched to intravenous treatment. In both groups, grade 3 or 4 toxicity was uncommon. Median overall survival was 14.7 months for the IHA group and 14.8 months for the intravenous group (hazard ratio 1.04 [95% CI 0.80-1.33], log-rank test p=0.79). Similarly, there was no significant difference in progression-free survival.


CONCLUSIONS
Our results showed no evidence of an advantage in progression-free survival or overall survival for the IHA group; thus continued use of this regimen cannot be recommended outside of a clinical trial.
Kerr
David J
DJ
Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, OX2 6HE, Oxford, UK. david.kerr@clinical-pharmacology.oxford.ac.uk
McArdle
Colin S
CS
Ledermann
Jonathan
J
Taylor
Irving
I
Sherlock
David J
DJ
Schlag
Peter M
PM
Buckels
John
J
Mayer
David
D
Cain
Dionne
D
Stephens
Richard J
RJ
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D005858:Germany / Q000453:epidemiology; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000009:adverse effects / Q000191:economics / Q000379:methods; D007262:Infusions, Intravenous; D007494:Ireland / Q000453:epidemiology; D017567:Karnofsky Performance Status; D002955:Leucovorin / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016019:Survival Analysis; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology
D000964:Antimetabolites, Antineoplastic; D002955:Leucovorin; D005472:Fluorouracil