What is the role and impact of molecular markers on treatment decisions in the adjuvant setting?

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				<td style="padding: 0 0 0 10px;" class="fondblanc"><h1>What is the role and impact of molecular markers on treatment decisions in the adjuvant setting?</h1>
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David J Kerr</h2>
<p>Despite curative surgery for localised disease, approximately 40% of colorectal cancer patients will eventually relapse.&nbsp; In patients with Stage III disease, adjuvant chemotherapy has been shown to lead to definite improvements in survival. The situation for those with Stage II disease is more uncertain, with up to 80% thought to be cured by surgery alone.&nbsp; Therefore, there exists a need to identify, pre-treatment, those Stage II patients who would benefit from adjuvant chemotherapy and molecular markers may give us important insight into this challenge.&nbsp; Individualised therapy currently is routinely based on clinical observation and drug pharmacokinetics to modulate drug dose and side effects.&nbsp; Increasingly however, molecular markers of the tumour and the pharmacogenomic profile of the patient will be taken into account when selecting the appropriate chemotherapy.&nbsp; <br />
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The VICTOR study recruited approximately 2500 patients who had undergone apparently curative surgery and chemotherapy/radiotherapy if clinically mandated.&nbsp; Subjects were randomised to receive either the selective COX-2 inhibitor, rofecoxib, or an identical looking placebo.&nbsp; The primary end point of the study was 3 year disease free survival and a substudy allowed detailed description of the cardiovascular side effect pattern associated with rofecoxib.&nbsp; Paraffin embedded tissue has been collected from the primary resection material from this trial, as has blood which allowed extraction of germline DNA from 1000 patients.&nbsp; This has permitted collaboration with the colorectal genetics team led by Ian Tomlinson and Richard Houlston and has led to identification of a number of SNPs associated with cancer causation.&nbsp; This work is being extended to detect germline SNPs associated with prognosis and toxicity of chemotherapy.&nbsp; The follow-up study Quasar II, is currently recruiting patients and is comparing response rates to a new anti-angiogenic agent bevacizumab (Avastin), used in combination with a standard chemotherapy, capecitabine (Xeloda), against capecitabine chemotherapy alone.&nbsp; The trial is also studying known and novel prognostic and predictive markers of response and toxicity.&nbsp; These in depth studies of tumour biomarkers and pharmacogenetics will enable researchers to better understand the observed individual differences in treatment outcome and make progress along the path to personalised treatment.&nbsp; Once validated in large scale randomised clinical trials with adequate statistical power, the selection of patients for personalized medicine may become incorporated into routine clinical practice.</p></td>
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