Correlation of markers of oxidative damage and circulating IL6 levels with survival following treatment with bevacizumab in metastatic colorectal cancer patients.

e21024 Background: Angiogenesis drives cancer growth, tumour progression and metastases. Hypoxic tumours initiate recruitment of their own blood supply and enhance expression of vascular endothelial growth factor (VEGF). Bevacizumab is a recombinant humanised monoclonal anti-VEGF antibody which prevents VEGF binding to its receptors and improves overall survival in metastatic colorectal cancer patients when combined with cytotoxic chemotherapy. Currently, Bevacizumab is indicated as a first line treatment in all metastatic colorectal cancer patients, however only 38-44% of these patients will have a response to treatment. There is no good marker to predict treatment response. The role of inflammation and oxidative damage in driving angiogenesis and clinical response to bevacizumab is poorly understood. The aim of this study was to investigate the levels of oxidative damage and inflammation in the tissue and in the circulation of patients receiving Bevacizumab. Methods: Tissue from 80 patients was constructed into tissue microarrays (TMAs) and screened by immunohistochemistry for the levels of a DNA adduct marker 8oxodG and a lipid peroxidation marker 4HNE in addition to Ki67 status. Serum was screened for 8oxodG, 4HNE and the inflammatory cytokines; IL1β, IL6, IL8, TNFα and pro-angiogenic factors; Ang 2, TGFβ, VEGF using ELISA. Data was correlated with patient survival following Bevacizumab treatment. Results: 8oxodG stromal nuclear positivity significantly correlated with survival following bevacizumab (p=0.035) and this was independent of cell proliferation status. Following multivariate analysis, circulating IL6 levels also significantly correlated with survival following bevacizumab treatment (p=0.01). Using linear regression, circulating levels of 8oxodG correlated with IL6 levels (p=0.016). Circulating Ang 2 levels correlated with IL6 (p=0.006). Conclusions: We have shown for the first time that levels of a DNA adduct marker 8oxodG and circulating levels of IL6 correlate with survival in metastatic patients receiving Bevacizumab.

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Association between bevacizumab-related hypertension and response to treatment in metastatic colorectal cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e14636 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e14636-e14636

Author(s):

Isabel Jose Dionisio de Sousa ◽

João Casalta-Lopes ◽

Joana Rodrigues ◽

Ana Pais ◽

Nuno Bonito ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Response To Treatment ◽

Colorectal Cancer Patients

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A retrospective analysis of periodontitis during bevacizumab treatment in metastatic colorectal cancer patients

International Journal of Clinical Oncology ◽

10.1007/s10147-012-0478-5 ◽

2012 ◽

Vol 18 (6) ◽

pp. 1020-1024 ◽

Cited By ~ 6

Author(s):

Kohei Ogawa ◽

Takao Ueno ◽

Ken Kato ◽

Hitoshi Nishitani ◽

Kohei Akiyoshi ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Retrospective Analysis ◽

Cancer Patients ◽

Bevacizumab Treatment ◽

Colorectal Cancer Patients

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Cetuximab could be more effective without prior bevacizumab treatment in metastatic colorectal cancer patients

OncoTargets and Therapy ◽

10.2147/ott.s89241 ◽

2015 ◽

pp. 3329 ◽

Cited By ~ 8

Author(s):

Yasuyoshi Sato ◽

Satoshi Matsusaka ◽

Mitsukuni Suenaga ◽

Eiji Shinozaki ◽

Nobuyuki Mizunuma

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Bevacizumab Treatment ◽

Colorectal Cancer Patients

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Does nutritional status affect treatment tolarability, response, and survival in metastatic colorectal cancer patients? Results of prospective multicenter study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.70 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 70-70

Author(s):

Senem Karabulut ◽

İzzet Dogan ◽

Çiğdem Usul Afşar ◽

Mehmet Karabulut ◽

Sule Karaman ◽

...

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Nutritional Status ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Multicenter Study ◽

Cytotoxic Chemotherapy ◽

Response To Treatment ◽

Severe Malnutrition ◽

Colorectal Cancer Patients

70 Background: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients. Methods: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status were evaluated on the basis of NRI, BMI and WL before the first chemotherapy, after the first and second chemotherapy. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRIs were examined in 3 categories as ‘no malnutrition’ (NRI >97.5), ‘moderate malnutrition’ (97.5 ≥ NRI ≥83.5) or ‘severe malnutrition’ (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on RECIST 1.1 and CTCAE version 4.0 respectively. Results: 137 mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients, 84% of them source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was 24 %. Moderate / severe malnutrition was associated with multipl site of metastases, WHO PS of 1, over the median value of CEA/CA 19-9 levels (p=0.003, p=0.03, p<0.001, and p=0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p<0.001 and p<0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p=0.02 and p=0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95 %CI, 5.6-7.6) vs 11.9 moths (95 % CI, 11.1-12.7) respectively, p<0.001]. Conclusions: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.

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An exploratory biomarker study in metastatic tumors from colorectal cancer patients treated with bevacizumab

The International Journal of Biological Markers ◽

10.5301/jbm.5000097 ◽

2015 ◽

Vol 30 (1) ◽

pp. 73-80 ◽

Cited By ~ 3

Author(s):

Francesco Sclafani ◽

Lorenza Rimassa ◽

Piergiuseppe Colombo ◽

Annarita Destro ◽

Sergio Stinco ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Cancer Patients ◽

Objective Response ◽

Predictive Biomarkers ◽

Response To Treatment ◽

Effective Treatment Option ◽

Primary Tumors ◽

Pten Loss ◽

Colorectal Cancer Patients

Aims Inhibition of angiogenesis is an effective treatment option for metastatic colorectal cancer. Predictive biomarkers to select patients who are most likely to benefit from this therapeutic strategy are lacking. We conducted a pilot, retrospective biomarker study in a cohort of metastatic colorectal cancer patients treated with bevacizumab. The objectives of this study were to evaluate the prognostic value of biomarker expression in metastases and to compare their expression in paired tumor specimens. Materials and methods Eligible patients were treated with a bevacizumab-containing therapy; from these patients, tumor tissue from metastases was available. PTEN, PI3K p110a, c-MET, and CAIX were analyzed by immunohistochemistry. Results Forty-two patients received bevacizumab, 13 (31%) with first-line and 29 (69%) with second-line chemotherapy. Expression of CAIX, PI3K p110a, and c-MET in metastases did not predict objective response. PTEN loss was associated with response to treatment (p=0.02) and this association remained significant after adjusting for prognostic variables (p=0.006). However, no association with survival outcomes was found. In 32 patients (76%) with available paired specimens, we observed an equal expression between primary tumors and corresponding metastases in 75% of cases for CAIX in epithelial tumor cells, 56% for CAIX in stromal cells, 63% for PTEN, and 87% for c-MET. Conclusion PTEN loss in metastases appears to be associated with response to bevacizumab-based therapy. However, larger studies are necessary to confirm the potential role of the PI3K/AKT/mTOR pathway in modulating the therapeutic effect of bevacizumab. Tumor heterogeneity should be taken into consideration when analyzing tumor tissues for biomarker studies.

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