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/m(2), fluorouracil bolus 400 mg(2) and 22-h infusion 600 mg/m(2), day 1 and 2, repeated every 14 days), or IHA chemotherapy designed to be equitoxic (folinic acid 200 mg/m(2), fluorouracil 400 mg/m(2) over 15 mins and 22-h infusion 1600 mg/m(2), day 1 and 2, repeated every 14 days). The primary endpoint was overall survival, and analysis was by intention to treat. Findings 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. Interpretation 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.