Chemotherapy delivered via the hepatic artery following surgical resection of liver metastases arising from colorectal cancer does not improve survival.

Nelson RL, Freels S

Published Online:

October 7, 2009

Patients who die of colorectal cancer usually die from, or at least with, liver metastases. On the other hand, isolated liver metastases can, on occasion, be resected with a chance of cure, if metastatic disease is not present elsewhere. After liver resection is performed for colorectal cancer metastases, the most common site of treatment failure is in the remaining liver. For that reason it has been proposed that chemotherapy be given in the hepatic artery after surgery to treat microscopic disease in the remaining liver.
This systematic review assesses the randomised trials that have addressed the effective ness of this additional chemotherapy. Seven studies have been published in this field, and the combined analysis shows that survival is not improved by hepatic artery chemotherapy.

Abstract (click to read)

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.

Objectives:

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.

Search strategy:

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, 2008.

Selection criteria:

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

Data collection and analysis:

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.

Main 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.

Authors' 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.

This record should be cited as:

Nelson RL, Freels S. Hepatic artery adjuvant chemotherapy for patients having resection or ablation of colorectal cancer metastatic to the liver. Cochrane Database of Systematic Reviews 2006, Issue 4. Art. No.: CD003770. DOI: 10.1002/14651858.CD003770.pub3

Assessed as up to date:

July 31, 2006

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Primary Review Group:

Colorectal Cancer Group

Health topics:

Cancer > Colorectal > Medical & adjuvant therapy

Gastroenterology > Cancer: colorectal > Medical & adjuvant therapy

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Chemotherapy delivered via the hepatic artery following surgical resection of liver metastases arising from colorectal cancer does not improve survival.

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