Literature DB >> 26307753

High pKDR immunohistochemical expression is an unfavourable prognostic biomarker in patients with advanced colorectal cancer treated with chemotherapy plus bevacizumab.

J Garde-Noguera1, M Gil-Raga2, E Evgenyeva3, J A García4, A Llombart-Cussac5, C Camps-Herrero6,7.   

Abstract

PURPOSE: To analyse the prognostic role of the immunohistochemical expression of pKDR in patients with advanced colorectal cancer treated with oxaliplatin and fluoropyrimidines combination chemotherapy with or without bevacizumab.
METHODS: Retrospective multicentre study, carried out at four hospitals in the Valencian Community (Spain). Patients evolution was compared based on the immunohistochemical expression of pKDR, classified using 4 categories: 0 (undetectable), 1 (mild), 2 (moderate) and 3 (high intensity). Patients were divided into two groups for the analysis: group 1 with low expression (0-1) vs. group 2 with high expression (2-3).
RESULTS: Histological samples for the pKDR analysis were available for 84 of the 112 patients selected. Seven (8.3 %) had undetectable or mild expression of pKDR (Group 1) and 77 (91.7 %) showed moderate or high expression of pKDR (Group 2). Response rate in Group 1 was 100 % compared to 54.2 % in Group 2 (p = 0.019). Progression-free survival (PFS) (15 vs. 12 months, p = 0.4) and overall survival (OS) (28 vs. 22 months, p = 0.09) were numerically but not significantly higher in patients from Group 1 vs. Group 2. Patients from Group 2 who received bevacizumab presented a significantly higher PFS (13 vs. 11, p = 0.015) and a numerically higher OS (23 vs. 17 months, p = 0.27) than those treated exclusively with chemotherapy.
CONCLUSIONS: Our results suggest that the absence or low expression of pKDR is associated with a better prognostic profile in patients with advanced colorectal cancer treated with chemotherapy and bevacizumab. Patients with a high pKDR expression benefit from the combination of chemotherapy with bevacizumab.

Entities:  

Keywords:  Bevacizumab; Biomarkers; Colorectal cancer; pKDR

Mesh:

Substances:

Year:  2015        PMID: 26307753     DOI: 10.1007/s12094-015-1378-8

Source DB:  PubMed          Journal:  Clin Transl Oncol        ISSN: 1699-048X            Impact factor:   3.405


  25 in total

Review 1.  Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy.

Authors:  R K Jain
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2.  Lactate dehydrogenase 5 expression in operable colorectal cancer: strong association with survival and activated vascular endothelial growth factor pathway--a report of the Tumour Angiogenesis Research Group.

Authors:  Michael I Koukourakis; Alexandra Giatromanolaki; Efthimios Sivridis; Kevin C Gatter; Adrian L Harris
Journal:  J Clin Oncol       Date:  2006-08-08       Impact factor: 44.544

Review 3.  Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis.

Authors:  M J Karkkainen; T V Petrova
Journal:  Oncogene       Date:  2000-11-20       Impact factor: 9.867

Review 4.  Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy.

Authors:  Rakesh K Jain
Journal:  Science       Date:  2005-01-07       Impact factor: 47.728

5.  Pharmacology and pharmacodynamics of bevacizumab as monotherapy or in combination with cytotoxic therapy in preclinical studies.

Authors:  Hans-Peter Gerber; Napoleone Ferrara
Journal:  Cancer Res       Date:  2005-02-01       Impact factor: 12.701

6.  Fetal liver kinase 1 is a receptor for vascular endothelial growth factor and is selectively expressed in vascular endothelium.

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Journal:  Proc Natl Acad Sci U S A       Date:  1993-08-15       Impact factor: 11.205

7.  Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study.

Authors:  Leonard B Saltz; Stephen Clarke; Eduardo Díaz-Rubio; Werner Scheithauer; Arie Figer; Ralph Wong; Sheryl Koski; Mikhail Lichinitser; Tsai-Shen Yang; Fernando Rivera; Felix Couture; Florin Sirzén; Jim Cassidy
Journal:  J Clin Oncol       Date:  2008-04-20       Impact factor: 44.544

8.  Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer.

Authors:  Herbert Hurwitz; Louis Fehrenbacher; William Novotny; Thomas Cartwright; John Hainsworth; William Heim; Jordan Berlin; Ari Baron; Susan Griffing; Eric Holmgren; Napoleone Ferrara; Gwen Fyfe; Beth Rogers; Robert Ross; Fairooz Kabbinavar
Journal:  N Engl J Med       Date:  2004-06-03       Impact factor: 91.245

9.  Expression of vascular endothelial growth factor and its receptor, KDR, correlates with vascularity, metastasis, and proliferation of human colon cancer.

Authors:  Y Takahashi; Y Kitadai; C D Bucana; K R Cleary; L M Ellis
Journal:  Cancer Res       Date:  1995-09-15       Impact factor: 12.701

10.  The significance of combining VEGFA, FLT1, and KDR expressions in colon cancer patient prognosis and predicting response to bevacizumab.

Authors:  Shu-Dong Zhang; Cian M McCrudden; Chen Meng; Yao Lin; Hang Fai Kwok
Journal:  Onco Targets Ther       Date:  2015-04-15       Impact factor: 4.147

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