Elsevier

Clinical Oncology

Volume 24, Issue 6, August 2012, Pages 432-442
Clinical Oncology

Overview
The Role of Biological Agents in the Resection of Colorectal Liver Metastases

https://doi.org/10.1016/j.clon.2012.01.002Get rights and content

Abstract

Surgically resecting liver metastases from colorectal cancer (CLMs) offers the only potentially curative option. Chemotherapy-induced downsizing of CLMs increases the proportion of patients with resectable metastases. Several recent studies have reported that adding a biological agent such as cetuximab, panitumumab or bevacizumab to chemotherapy could further increase response and resectability rates. This overview discusses the reported resection rates for biological agents combined with chemotherapy and the difficulties of cross-trial comparisons, the pre-, peri- and postoperative roles of biological agents, particularly with regards to comparisons of surgical complications, and ongoing clinical trials in which the resectability of CLMs is a predefined end point. Currently, targeted therapies combined with chemotherapy probably increase the resection rate of CLMs, although this has been shown in only one phase III randomised study and it is difficult to draw definitive conclusions about the relative efficacy and safety of the different available biological agents in terms of converting unresectable CLMs to resectable lesions. Available data for each of them are discussed. More data from phase III trials are expected to confirm the utility of the different biological agents in converting patients with unresectable CLMs to a resectable status.

Section snippets

Statement of Search Strategies Used and Sources of Information

A search was carried out in Medline, Embase, Biosis Previews, Web of Science, Web of Knowledge, the Cochrane Library and ClinicalTrials.gov with the assistance of a medical information specialist at Gardiner-Caldwell Communications, Macclesfield, UK, on 20 May 2010. The search algorithm of MeSH-used terms was the following: (“General Surgery” [Mesh] OR “Surgical Procedures, Operative” [Mesh] OR “surgery” [Subheading] OR “liver resection” [All Fields] OR “hepatic resection” [All Fields]) AND

Resection Rates

Several studies have evaluated the impact of bevacizumab, cetuximab and panitumumab in combination with chemotherapy on resection rates in patients with CLMs. However, patient selection, resectability criteria before and after treatment, and resection not being a prespecified end point in most studies makes cross-study comparisons difficult to interpret.

Bevacizumab

The phase III, placebo-controlled NO16966 trial reported a resection rate of 8.4% in the intent-to-treat population when bevacizumab was added

Pathological Response

Assessing the response on computed tomography may not be sufficient to measure the efficacy of a systemic treatment with chemotherapy and a monoclonal antibody. Recent reports have indicated that the pathohistological response to a systemic treatment could become a very relevant indicator of a patient’s prognosis [50], [51]. The pathological tumour response after preoperative therapy can be evaluated by assessing the presence of residual viable tumour cells [52]. This method of evaluation is

Postoperative Complication Rates

In general, liver surgery is feasible after the administration of antibody-containing combination regimens. Complications, such as delayed wound healing, gastrointestinal perforation or bleeding have been reported when bevacizumab is administered and could potentially interfere with surgery [25], [26], [34], [57], [58], [59]. However, more recent reports have shown that liver surgery can be safely carried out without a significant increase in postoperative complications when bevacizumab is

Future Directions

Several phase II and III clinical trials involving the use of bevacizumab, cetuximab or panitumumab with predefined end points that include CLM resection rate as well as postoperative safety are ongoing in patients with mCRC. In particular, given the need for significant responses when treating mCRC, potentially more active triplet regimens, such as FOLFOXIRI, are being investigated in clinical trials in combination with biological agents. If initial reports are confirmed, it is possible that

Conclusions

Combination chemotherapy has been shown to be capable of downsizing CLMs and increasing CLM resection rates, potentially improving patient survival. At least in some patients, liver resection is associated with cure.

In comparison with chemotherapy doublets alone, combinations with antibodies, as well as chemotherapy triplets, seem to further improve the results: numerous phase II/III trials have reported higher RECIST response rates compared with chemotherapy only. Higher response rates are

Acknowledgements

Support for third-party writing assistance for this manuscript was provided by F. Hoffmann-La Roche Ltd.

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