Circulating tumor cell (CTC) count and epithelial growth factor receptor expression on CTCs as biomarkers for cetuximab efficacy in advanced colorectal cancer.

BACKGROUND/AIM The purpose of this study was to establish whether CTC count and epidermal growth factor receptor (EGFR) expression in CTCs predicted outcome in patients with advance colorectal cancer (ACC) receiving cetuximab as third-line treatment. PATIENTS AND METHODS Between October 2008 and March 2011, 63 patients with KRAS wild-type ACC were treated with cetuximab-containing chemotherapy at the Cancer Institute Hospital. We measured the CTC count and EGFR expression on CTCs using the CellSearch System (Veridex LLC, NJ, USA). RESULTS Nineteen patients (30%) with a high number of CTCs had a significantly lower overall survival compared with 44 patients with a low number of CTCs. No significant difference was observed in progression-free survival between the two groups. Out of the 33 patients positive for CTCs (one or more CTC), seven patients (21%) were positive for EGFR expression. No statistically significant difference was observed in clinical outcome between EGFR-positive and EGFR-negative patients. CONCLUSION A high CTC count predicted reduced overall survival in patients with ACC treated with cetuximab-combination chemotherapy as third-line treatment. These results suggest that the assessment of CTCs might provide with important prognostic information for such patients.

[1]  S. Matsusaka,et al.  Circulating tumor cells as a surrogate marker for determining response to chemotherapy in Japanese patients with metastatic colorectal cancer. , 2012, Journal of Clinical Oncology.

[2]  I. Nagtegaal,et al.  Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents. , 2010, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  K. Chìn,et al.  Circulating tumor cells as a surrogate marker for determining response to chemotherapy in patients with advanced gastric cancer , 2010, Cancer science.

[4]  N. Tsubota,et al.  Circulating Tumor Cell as a Diagnostic Marker in Primary Lung Cancer , 2009, Clinical Cancer Research.

[5]  P. Gibbs,et al.  Prospective cost-effectiveness analysis of cetuximab in metastatic colorectal cancer: evaluation of National Cancer Institute of Canada Clinical Trials Group CO.17 trial. , 2009, Journal of the National Cancer Institute.

[6]  E. Higashihara,et al.  Prognostic significance of circulating tumor cells in patients with hormone refractory prostate cancer. , 2009, The Journal of urology.

[7]  T. Greten,et al.  Tumour-Associated Transcripts and EGFR Deletion Variants in Colorectal Cancer in Primary Tumour, Metastases and Circulating Tumour Cells , 2008, Cellular oncology : the official journal of the International Society for Cellular Oncology.

[8]  Michael Morse,et al.  Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  H. Scher,et al.  Circulating Tumor Cell Analysis in Patients with Progressive Castration-Resistant Prostate Cancer , 2007, Clinical Cancer Research.

[10]  G. T. Budd,et al.  Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall Survival , 2006, Clinical Cancer Research.

[11]  A. Italiano,et al.  Epidermal growth factor receptor (EGFR) status in primary colorectal tumors correlates with EGFR expression in related metastatic sites: biological and clinical implications. , 2005, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  L. Schwartz,et al.  Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[13]  R. Berardi,et al.  Epidermal growth factor receptor (EGFR) status in primary colorectal tumors does not correlate with EGFR expression in related metastatic sites: implications for treatment with EGFR-targeted monoclonal antibodies. , 2004, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  Alison Stopeck,et al.  Circulating tumor cells, disease progression, and survival in metastatic breast cancer. , 2004, The New England journal of medicine.

[15]  M. Christian,et al.  [New guidelines to evaluate the response to treatment in solid tumors]. , 2000, Bulletin du cancer.

[16]  Z. Hua Cetuximab Monotherapy and Cetuximab plus Irinotecan in Irinotecan-Refractory Metastatic Colorectal Cancer , 2006 .