Originally published as JCO Early Release 10.1200/JCO.2005.03.8166 on February 27 2006

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Hepatic Arterial Infusion Versus Systemic Therapy for Hepatic Metastases From Colorectal Cancer: A Randomized Trial of Efficacy, Quality of Life, and Molecular Markers (CALGB 9481)

Nancy E. Kemeny, Donna Niedzwiecki, Donna R. Hollis, Heinz-Josef Lenz, Robert S. Warren, Michelle J. Naughton, Jane C. Weeks, Elin R. Sigurdson, James E. Herndon, II, Chunfeng Zhang, Robert J. Mayer

From the Memorial Sloan-Kettering Cancer Center, New York, NY; Cancer and Leukemia Group B Statistical Center, Durham, NC; University of Southern California, Los Angeles, Los Angeles; University of California at San Francisco, San Francisco, CA; Wake Forest University School of Medicine, Winston-Salem, NC; Dana-Farber Cancer Institute, Boston, MA; and Fox Chase Cancer Center, Philadelphia, PA

Address reprint requests to Nancy E. Kemeny, MD, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021; e-mail: kemenyn{at}mskcc.org

PURPOSE: Hepatic metastases derive most of their blood supply from the hepatic artery; therefore, for patients with hepatic metastases from colorectal cancer, hepatic arterial infusion (HAI) of chemotherapy may improve outcome.

METHODS: In a multi-institutional trial, 135 patients were randomly assigned to receive HAI versus systemic bolus fluorouracil and leucovorin. The primary end point was survival; secondary end points were response, recurrence, toxicity, quality of life, cost, and the influence of molecular markers.

RESULTS: Overall survival was significantly longer for HAI versus systemic treatment (median, 24.4 v 20 months; P = .0034), as were response rates (47% and 24%; P = .012) and time to hepatic progression (THP; 9.8 v 7.3 months; P = .034). Time to extrahepatic progression (7.7 v 14.8 months; P = .029) was significantly shorter in the HAI group. Quality-of-life measurements showed improved physical functioning in the HAI group at the 3- and 6-month follow-up assessments. Toxicity included grade 3 neutropenia (2% and 45%; P < .01), stomatitis (0% and 24%; P < .01), and bilirubin elevation (18.6% and 0; P < .01) in the HAI and systemic treatment groups, respectively. A greater proportion of men versus women receiving HAI experienced biliary toxicity (37% and 15%, respectively; P = .05). For HAI patients with thymidylate synthase levels in tumor less than or 4, the median survival was 24 and 14 months, respectively (P = .17).

CONCLUSION: HAI therapy increased overall survival, response rate, THP, and was associated with better physical functioning compared with systemic therapy. Additional studies need to address the overall benefit and cost of new chemotherapy agents versus HAI alone or the combination of HAI with new agents.

Supported in part by Grant No. CA31946 from the National Cancer Institute to the Cancer and Leukemia Group B (CALGB; Richard L. Schilsky, MD, Chairman) and Grant No. CA23318 to the Eastern Cooperative Oncology Group. The following institutions were supported by Grant Nos. listed in parentheses: Memorial Sloan-Kettering Cancer Center (CA77651); CALBG Statistical Center (CA33601); University of Southern California and University of California at San Francisco (CA60138); Wake Forest University School of Medicine (CA03927); Dana-Farber Cancer Institute (CA32291); and Fox Chase Cancer Center (CA27525).

The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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