Meta-analysis group in cancer: reappraisal of hepatic arterial infusion in the treatment of non resectable liver metastases from colorectal cancer

Abstract

BACKGROUND: Metastases confined to the liver cause substantial morbidity and mortality for patients with colorectal cancer. The results of several randomized clinical trials conducted to study the effectiveness of hepatic arterial infusion (HAI) of fluoropyrimidines for the treatment of such patients have suggested that this treatment, as compared with systemic administration of fluoropyrimidines, increases the likelihood of tumor response. However, the impact of HAI on survival is unclear.

PURPOSE: A meta-analysis was carried out to provide an objective and quantitative appraisal of the benefits of HAI in terms of tumor response rate and overall patient survival.

METHODS: The meta-analysis was based on individual data provided by the principal investigators of six individual trials and on summary data for one trial. Of the seven trials, five compared HAI with floxuridine (5-fluoro-2'-deoxyuridine; FUDR) and intravenous chemotherapy (IVC) with FUDR (three trials) or fluorouracil (5-FU) (two trials), and two compared HAI with FUDR and an ad libitum control group in which some patients could be left untreated. Response data were analyzed by use of a Mantel-Haenszel test on all randomized patients. Survival data were analyzed by the use of a stratified logrank test. Multivariate analyses were performed with the use of the logistic regression model for tumor response and the Cox regression model for survival. All P values resulted from two-sided statistical tests. The analyses were performed by an independent secretariat and were reviewed by the collaborators.

RESULTS: The tumor response rate was 41% for patients allocated to HAI with FUDR (complete response [CR], 3%; partial response [PR], 38%) compared with 14% for patients allocated to IVC with FUDR or 5-FU (CR, 2%; PR, 12%). This difference was highly significant, with a response odds ratio of 0.25 (95% confidence interval = 0.16–0.40; P<10–10). Survival analyses showed a statistically significant advantage for HAI with FUDR compared with control when all trials were taken into account (P = .0009) but not when the survival analysis was restricted to trials comparing HAI with FUDR and IVC with FUDR or 5-FU (P = .14).

CONCLUSION: These results confirm that HAI can achieve much higher tumor response rates than systemic chemotherapy in patients with liver metastases from colorectal cancer.

IMPLICATIONS: The therapeutic benefit of use of HAI with FUDR in these patients should be judged together, with an overall evaluation of this therapy in terms of convenience, toxicity, and costs. These end points should be considered in addition to tumor response and survival in further trials involving HAI.