Journal of IMAB - Annual Proceeding (Scientific Papers)
Publisher: Peytchinski, Gospodin Iliev
ISSN: 1312 773X (Online)
Issue: 2016, vol. 22, issue 1
Subject Area: Medicine
Pages: 1039-1044
DOI: 10.5272/jimab.2016221.1039
Published online: 10 March 2016

J of IMAB 2016 Jan-Mar;22(1):1039-1044
Assia Konsoulova1* Corresponding Autor, Ivan Donev1*, Nikolay Conev1, Sonya Draganova1, Nadezhda Petrova2, Eleonora Dimitrova1, Hristo Popov2, Kameliya Bratoeva3, Petar Ghenev2.
1) Medical Oncology Clinic, University Hospital “St. Marina”- Varna
2) General and specialized pathology Clinic, University Hospital “St. Marina”- Varna
3) Division of pathophysiology, Department of Physiology and pathophysiology, Medical University, Varna, Bulgaria.
* Those authors participated with equal contribution to this publication.

Purpose: Colorectal cancer is the second leading cause of cancer mortality in the USA. According to Bulgarian National Statistics Institute, 2370 colon and 1664 rectal cancer cases were diagnosed in 2012 with total number of patients 29995. Adding bevacizumab to chemotherapy in patients with metastatic disease improves progression-free survival (PFS) but no predictive markers have been proven in the clinical practice. In our study we examined two tissue biomarkers that may correlate with response to bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer.
Patients and Methods:  54 patients with metastatic colorectal cancer were assigned to first line 5-Fu-based chemotherapy with/without bevacizumab. The primary end point was PFS, with additional determination of response and toxicity. Paraffin-embedded samples from primary tumors were collected from all 54 patients. Expression levels of two tumor biomarkers VEGFR-2 and Neuropilin 1 (NP-1) were evaluated with immunohistochemistry.
Results: The median PFS for the group treated with CT/Bev was 8.8 months, compared with 5.4 months for the group with chemotherapy alone (95% CI, log-rank test P =0.003). The corresponding overall response rates were 19.3% and 10.2% respectively (P < 0.05 for CT/Bev vs CT). Patients with low NP-1 had statistically significant prolongation of PFS as compared to those with high NP-1 (95% CI, log rank test p= 0.017). Patients with low NP-1 appeared to experience a larger bevacizumab treatment effect in terms of PFS (p=0,049,HR 0.333, 95% CI, 0.111 to 0.995) than patients with high NP-1.
Conclusion: The addition of bevacizumab to 5-Fu based chemotherapy improves PFS for patients with metastatic colorectal cancer. Expression of tumor NP-1 is a potential biomarker candidate for prediction of clinical outcome in patients with metastatic colorectal cancer, treated with first line chemotherapy plus bevacizumab.

Key words: colorectal, bevacizumab, VEGFR-2, biomarkers, neuropillin-1,

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Please cite this article in PubMed Style or AMA (American Medical Association) Style:
Konsoulova A, Donev I, Conev N, Draganova S, Petrova N, Dimitrova E, Popov H, Bratoeva K, Ghenev P. First line 5-Fu-based chemotherapy with/without Bevacizumab for Metastatic Colorectal Cancer: tissue biomarker candidates. J of IMAB. 2016 Jan-Mar;22(1):1039-1044.

Correspondence to: Dr. Assia Konsoulova-Kirova, University Hospital “Sveta Marina”; 1, Hristo Smirnenski Blvd., 9001 Varna, Bulgaria; E-mail:

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Received: 11 December 2015
Published online: 10 March 2016

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