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In Reply

Simone Mocellin

Surgery Branch, Department of Oncological and Surgical Sciences, University of Padova, Padova, Italy

We are worried about the idea that the title of our meta-analysis¹ is attracting readers like Power and Leonard and others (see commentary by Pestalozzi et al²) more than the content of our work. Should this be the case, we would like to briefly remember that in our quantitative review, we summarize the available evidence (10 phase III randomized controlled trials enrolling 1,277 patients) on the use of fluoropyrimidine-alone hepatic arterial infusion (HAI) for the treatment of patients with unresectable liver metastases from colorectal cancer.

We clearly demonstrated two points: (1) as regards its activity, fluoropyrimidine HAI yields tumor response rates equal to or lower than modern systemic chemotherapy regimens, and (2) as regards its efficacy, fluoropyrimidine HAI does not improve survival compared with systemic chemotherapy regimens that are currently outdated. Accordingly, we concluded that fluoropyrimidine HAI cannot be recommended for the treatment of patients with unresectable liver metastases from colorectal cancer. In other words, the currently available medical evidence does not warrant further use of such locoregional treatment (again, for the sake of precision, fluoropyrimidine-alone HAI).

We wonder why people like Power and Leonard so strongly disagree with this conclusion and write commentaries (almost completely off target, as we will explain later) to defend HAI. Like any other therapy, HAI must not be defended a priori, but rather on the basis of the available clinical findings. We would like to ask people like Power and Leonard how many more patients they believe should be treated with fluoropyrimidine HAI before we can accept the failure of this regimen and go ahead with testing newer regimens.

But let's come to the off-target comments of Power and Leonard. Although our meta-analysis concerns fluoropyrimidine-alone HAI, these authors support their disagreement with our conclusions by describing the anticancer activity (not efficacy, because no trial demonstrating any impact on survival exists) of modern-drug (eg, oxaliplatin) HAI combined with modern systemic chemotherapy regimens (evidence based exclusively on nonrandomized clinical trials). First of all, this means that they also believe that one era—that of fluoropyrimidine-alone HAI—is actually finished, as we concluded. Secondly, because this regimen is not useful for patients, we made the title of our paper end with a legitimate question: Is it the end of an era? Then, in the Discussion section, we did comment on the fact that the only modern way of further exploring the therapeutic potential of HAI is to use modern drugs and to combine HAI with modern systemic chemotherapy. (To support this potential therapeutic development we cited the same articles quoted by Power and Leonard.) That is, if an era has certainly ended, a new one might be on the horizon.

Overall, our feeling is that Power and Leonard (like others) have read the title of our meta-analysis and have been clouded by the provocative question in it, but they have not read the entire manuscript, which is a kind of sad thing. We truly hope that our meta-analysis can deliver readers (those willing to read the full text!) the right message: No evidence based on randomized controlled trials supports the routine use of HAI for the treatment of these unlucky patients, and any other HAI utilization is purely investigational.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

NOTES

published online ahead of print at www.jco.org on April 28, 2008

REFERENCES

1. Mocellin S, Pilati P, Lise M, et al: Meta-analysis of hepatic arterial infusion for unresectable liver metastases from colorectal coacer: The end of an era? J Clin Oncol 25:5649-5654, 2007[Abstract/Free Full Text]

2. Pestalozzi BC, Gruttadauria S, Clavien P-A: Hepatic arterial infusion: The beginning of the combination era. J Clin Oncol 26:2230-2231, 2008[Free Full Text]

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