Hepatic artery adjuvant chemotherapy for patients having resection or ablation of colorectal cancer metastatic to the liver.
BACKGROUND
Colorectal cancer metastatic to the liver, when technically feasible, is resected with a moderate chance of cure. The most common site of failure after resection is within the remaining liver. With this pattern of clinical failure in mind and in order to enhance survival, chemotherapy has been delivered directly to the liver post resection via the hepatic artery.


OBJECTIVE
To assess the effect of post hepatic resection hepatic artery chemotherapy on overall survival. Secondary objectives include adverse events related to the chemotherapy, the risk of intra-hepatic tumour recurrence and tumour free survival.


METHODS
Randomised trials were sought in MEDLINE; the Cochrane Central Register of Controlled Trials; the Cochrane Hepato-Biliary Group Controlled Trials Register; and through contact of trial authors and reference lists using key words: Colorectal, cancer, hepatic metastases, hepatic artery, chemotherapy. Searches were performed in December 2003.


METHODS
Trials in which patients having resection of colorectal cancer metastatic to the liver were randomised either to hepatic artery chemotherapy or any alternative treatment.


METHODS
Survival data were obtained principally from abstraction from survival curves in published studies using the method of Parmar. A study specific log hazard ratio and then combined effect log hazard ratio were calculated, as well as a combined Kaplan-Meier survival probability curve.


RESULTS
Seven randomised trials addressed this issue, encompassing 592 patients. No significant advantage was found in the meta-analysis for hepatic artery chemotherapy measuring overall survival and calculating survival based upon "intention to treat" (lnHR = 0.0848; favouring the control group, 95% confidence interval = -0.1189 to 0.2885, or a Hazard Ratio of 1.089, an 8.9% survival advantage for the control group, 95% CI of the HR = 0.887 - 1.334). Adverse events related to the hepatic artery therapy were common, including five therapy related deaths. Intra-hepatic recurrence was more frequent in the control group (97 patients versus 43 in the HAI group), though denominators are not reported, and additional outcomes could not be subjected to a combined analysis.


CONCLUSIONS
Though recurrence in the remaining liver happened less in the hepatic artery chemotherapy group, overall survival was not improved, and even favoured the control group, though not significantly. This added intervention cannot be recommended at this time.
Nelson
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Surgery, University of Illinois at Chicago, room 2204, m/c 957, 1740 West Taylor, Chicago, Illiniois, USA, 60612.
Freels
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D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary* / Q000601:surgery; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic
D000970:Antineoplastic Agents