Intrahepatic chemotherapy for colon cancer metastases – pro

The potential value of hepatic intra-arterial chemotherapy (HIAC) can be considered from several different perspectives. A fundamental assumption for this discourse requires that, in this evaluation, HIAC is being provided with the intent of providing regional hepatic therapy for metastatic hepatic disease. Despite advances in colon cancer (CRC) screening, surgical techniques, and several novel adjuvant agents, CRC continues to be a significant medical challenge. In the United States, approximately 130,000 cases of colon cancer are diagnosed annually. Of these patients, approximately 60% will ultimately develop metastatic disease, and <30% of the initial patient population will have disease confined to the liver.

Ample evidence exists in support of HIAC as the preferred route of administration of regional hepatic chemotherapy: it achieves higher intrahepatic drug concentrations and excellent tumor response rates when compared with other routes of administration. HIAC is an effective form of regional chemotherapy for hepatic metastases. Nearly all studies demonstrate a tendency toward or a significant decrease in hepatic tumor progression when HIAC is used. It is also clear from the data reviewed that regional control of hepatic disease without or independent of systemic disease control does not confer a survival advantage.

To date, the QOL of patients undergoing HIAC has not been adequately evaluated or compared with other treatment modalities. The studies available do not permit any conclusions about the QOL of patients receiving HIAC. Future studies should include QOL among the secondary outcomes in evaluating HIAC.

To date, 10 RCTs have been published, for a total of 1,277 patients enrolled. For tumor response rates, relative risks (RR) and their 95% CIs were obtained from raw data; for OS, hazard ratios (HRs) and their 95% CIs were extrapolated from the Kaplan-Meier survival curves.

Currently available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone for the treatment of patients with unresectable CRC liver metastases, at least as a first-line therapy.

Going to a different setting, the use of HAI of FUDR and systemic 5-FU/LV following resection of hepatic metastases clearly decreases local recurrence and can improve 2-year survival, and further study of HAI in this setting is warranted. Both hepatic and extrahepatic relapses remain a problem and, therefore, initial studies combining HAI with newer systemic agents, such as irinotecan and oxaliplatin, are under way. These should provide a framework to guide us as to which combination regimens are the most effective and well-tolerated. Ultimately, this should lead to randomized trials of HAI therapy plus systemic chemotherapy versus our most active systemic chemotherapy alone in order to determine the best approach to treating hepatic CRC metastases.

Evan S. Ong, MD, Madeleine Poirier, MDCM, MSc, FRCS(C) and N. Joseph Espat, MD, MS, FACS
Hepatic Intra-Arterial Chemotherapy Annals of Surgical Oncology 13:142-149 (2006)

S. Mocellin, P. Pilati, M. Lise, and D. Nitti
Meta-Analysis of Hepatic Arterial Infusion for Unresectable Liver Metastases From Colorectal Cancer: The End of an Era?
J. Clin. Oncol., December 10, 2007; 25(35): 5649 – 5654.

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