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Colorectal Cancer
Colorectal Liver Metastases – Enhancing Outcomes
Through Combination Treatments
a report by
Irving Taylor
Professor of Surgery, Vice Dean and Director of Medical Studies, University College London
Colorectal liver metastases (CRLMs) are common and can either As shown in Table 1, various chemotherapy regimes have been
present at the time of initial colorectal cancer diagnosis (synchronous) advocated and several have been subjected to prospective clinical
or develop subsequently (metachronous). There has been increasing trials. The overall conclusions are, in summary: folinic acid, fluorouracil
interest in the treatment of CRLMs in recent years due to the and irinotecan (FOLFIRI) and 5-fluorouracil (5-FU), leucovorin and
development of new therapies and improving prognosis. oxaliplatin (FOLFOX) are equally effective (response rates of 56 and
54%, respectively
8
); and 5-FU, leucovorin, oxaliplatin and irinotecan
A key factor in the treatment of CRLMs is the need for detailed (FOLFOXIRI) is superior to FOLFIRI
9
(response rates of 60 and 34%,
discussion of individual patients in a multidisciplinary environment respectively, and R0 resection rates of 36 and 12%, respectively).
involving specialists with a wide range of interests. Accordingly, a plan
of treatment and follow-up can be devised at an early stage. The Other studies have demonstrated response rates of between 8 and
importance of this approach cannot be overemphasised. 41% following administration of oxaliplatin- or irinotecan-based
regimes. Again, selection may be crucial in this regard. It would appear
Surgery that three-drug combinations have a higher response rate and a higher
Surgery is the most important treatment modality for patients with resection rate, without any significant impact on either toxicity or
CRLMs. Appropriate surgery in selected patients will result in long- surgical safety.
term survival of up to 40%.
1,2
This percentage has increased over the
last two decades. There have been developments in surgical technique, These studies are extremely important and demand our attention.
including portal vein embolisation and safer liver division and Patients with apparently unresectable disease who are otherwise fit
resection, as well as improvements in post-operative management. As should be considered for neoadjuvant therapy in a multidisciplinary
a result, resections are now more extensive and, due to improving setting. The role of biological agents in this situation has also been
expertise, are associated with reduced post-operative morbidity and extensively investigated. The two agents studied are bevacizumab
mortality. A general principle is to resect all macroscopic disease, (vascular endothelial growth factor [VEGF] monoclonal antibody) and
aiming for a potentially curative resection. In order to achieve this, it cetuximab (epidermal growth factor receptor [EGFR] monoclonal
may be necessary to combine surgical excision with ablation, e.g. antibody). Bevacizumab has been shown to improve the objective
radiofrequency ablation, intra-operatively or percutaneously in the response rate and prolong survival: in one study, the response rate was
post-operative period. Often this avoids an unacceptably dangerous 45–70% when combined with 5-FU, leucovorin and irinotecan.
10
major resection; for example, an extended right hemi-hepatectomy Cetuximab has been reported to result in resection rates of 19–30% in
can be combined with radiofrequency ablation of smaller lesions on unselected patients.
11
Patients refractory to conventional
the left side of the liver. However, it should be noted that initially only chemotherapy can be converted to cetuximab-based regimes, and
15–20% of patients are suitable for surgical resection.
3
As a result, an hence increase the total proportion of initially unresectable patients to
attempt to increase the resectability rate with additional treatments approximately 20%. It is suggested that resectability rate should be an
has been advocated. end-point in randomised trials.
Neoadjuvant Chemotherapy There is a concern that these agents will result in an increase in post-
There is increasing interest in the role of pre-operative or neoadjuvant operative morbidity and possible mortality. Studies have demonstrated
chemotherapy to downsize liver metastases in an attempt to achieve that post-operative morbidity is correlated with the number of cycles
resection of previously unresectable CRLMs. Accordingly, such of chemotherapy and not necessarily the type of chemotherapy.
treatment increases the proportion of patients able to achieve long-
term survival. Recent studies have described resection rates of up to
Irving Taylor is a Professor of Surgery, Vice Dean and Director
20% in patients with initially unresectable liver metastases, with five-
of Medical Studies at University College London. He has a
year survival rates in these patients approaching 50% (see Table 1).
4–7
particular clinical interest in surgical oncology and is
President of the European Society of Surgical Oncology
(ESSO). Professor Taylor is an elected member of the Royal
However, it should be emphasised that in order to achieve optimum
College of Surgeons of England and chairs its Professional
results, careful selection is essential. Recent studies have demonstrated
Standards Committee. He is also a case examiner for the
fitness to practice directorate of the General Medical Council.
a strong correlation between response rate to chemotherapy and
subsequent resection rate, which in selected patients may be 20–50%
E:
irving.taylor@ucl.ac.uk
compared with 1–20% in non-selected patients.
© TOUCH BRIEFINGS 2008 81
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