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Journal of Clinical Oncology, Vol 26, No 16 (June 1), 2008: pp. 2788-2789 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.17.1736
Hepatic Arterial Infusion Chemotherapy for Metatstases From Colorectal Cancer: Is It Really the End of an Era?Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY To the Editor: We read with interest the recently published meta-analysis of hepatic arterial infusional (HAI) chemotherapy for unresectable hepatic metastases from colorectal cancer.1 The authors analyzed 10 randomized trials published between 1987 and 2006 and ultimately concluded that HAI chemotherapy is associated with greater tumor response rates but not increased survival. The title of the article questions whether this is the end of an era, and the conclusions of the article state that "available evidence does not support the clinical or investigational use of fluoropyrimidine-based HAI alone, at least as a first-line therapy."1 We are not aware of any current debate regarding whether HAI chemotherapy should be used alone for unresectable metastases, a strategy long since abandoned at our institution. The standard way in which HAI chemotherapy is now administered is in combination with systemic chemotherapy, and this approach has shown remarkable efficacy in initial studies.2-4 Unfortunately, the tone of the title ("The End of an Era?") and the truncated conclusion in the abstract disregard recent data on combination therapy and are misleading to the reader. It must also be acknowledged that meta-analyses of this type have inherent limitations, making firm conclusions difficult. For example, only two of the trials disallowed cross over, whereas in four trials, it was clearly advocated, making survival a dubious end point for this analysis. Additionally, two of these 10 trials used fluorouracil rather than floxuridine (FUDR) for HAI therapy, which is well known to have a lower extraction rate and to be an ineffective regimen. Perhaps most importantly, all of the trials used HAI chemotherapy alone without systemic chemotherapy. Only in the last few sentences of the article do the authors refer to the current data on combined HAI and systemic chemotherapy, briefly acknowledging that this approach may have value. Perhaps if the authors had provided some details regarding recently published data on this approach, the reader would have a more appropriate context in which to interpret the meta-analysis. Data from our institution have shown that, in heavily pretreated patients with unresectable liver metastases, HAI FUDR and dexamethasone combined with various systemic chemotherapy combinations have excellent safety profiles and some of the highest response rates reported in the literature.2-4 For example, in a recently published phase I trial of HAI FUDR combined with two different systemic oxaliplatin combinations, response rates of 87% and 90% were demonstrated in a group of patients in whom 90% had been previously treated. Furthermore, median survival times in the two treatment groups were 22 and 36 months from the time of HAI therapy and 35 and 47 months from the time of initial diagnosis of metastatic disease.3 These are encouraging results found in a group of patients with limited effective systemic chemotherapy options. Although the era of HAI-based fluoropyrimidine therapy alone may have ended, the use of combination HAI and systemic chemotherapy is just beginning. The authors conclude that there is no support for HAI therapy alone, but this point is not emphasized, and the tone of the article is easily misconstrued to mean HAI therapy of any type. Current combinations of HAI and systemic chemotherapy have yielded some of the most promising data in this field and to suggest that the use and investigation of HAI chemotherapy are over is inappropriate. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Mocellin S, Pilati P, Lise M, et al: Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal cancer: The end of an era? J Clin Oncol 25:5649-5654, 2007 2. Kemeny N, Gonen M, Sullivan D, et al: Phase I study of hepatic arterial infusion of floxuridine and dexamethasone with systemic irinotecan for unresectable hepatic metastases from colorectal cancer. J Clin Oncol 19:2687-2695, 2001 3. Kemeny N, Jarnagin W, Paty P, et al: Phase I trial of systemic oxaliplatin combination chemotherapy with hepatic arterial infusion in patients with unresectable liver metastases from colorectal cancer. J Clin Oncol 23:4888-4896, 2005 4. Gallagher DJ, Capanu M, Raggio G, et al: Hepatic arterial infusion plus systemic irinotecan in patients with unresectable hepatic metastases from colorectal cancer previously treated with systemic oxaliplatin: A retrospective analysis. Ann Oncol 18:1995-1999, 2007
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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