OverviewThe Role of Biological Agents in the Resection of Colorectal Liver Metastases
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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