Evaluation of hypertension and proteinuria as markers of efficacy in antiangiogenic therapy for metastatic colorectal cancer
| Autor: | Andrew R Clamp, Gordon C Jayson, Leila Khoja, Ric Swindell, Jurjees Hasan, Gireesh C Kumaran, Nishanth Murukesh, Gregory Wilson, Ying-Kiat Zee, Mark P Saunders, Juan W. Valle |
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| Rok vydání: | 2013 |
| Předmět: |
Oncology
Adult Male Vascular Endothelial Growth Factor A medicine.medical_specialty Bevacizumab Colorectal cancer Angiogenesis Inhibitors Antineoplastic Agents Antibodies Monoclonal Humanized chemistry.chemical_compound Internal medicine medicine Humans Neoplasm Metastasis Survival rate Protein Kinase Inhibitors Survival analysis Aged Retrospective Studies Aged 80 and over Proteinuria Neovascularization Pathologic business.industry Surrogate endpoint Gastroenterology Retrospective cohort study Middle Aged medicine.disease Survival Analysis Surgery Vascular endothelial growth factor Survival Rate Treatment Outcome chemistry Hypertension Female medicine.symptom business Colorectal Neoplasms medicine.drug |
| Zdroj: | Journal of clinical gastroenterology. 48(5) |
| ISSN: | 1539-2031 |
| Popis: | BACKGROUND:: The vascular endothelial growth factor pathway is strongly implicated in cancer-related angiogenesis. Antiangiogenic agents such as bevacizumab commonly cause hypertension (HTN) and proteinuria (PTN), which may be biomarkers of response and clinical outcome. STUDY:: We conducted a retrospective analysis of patients with histologically proven metastatic colorectal cancer (mCRC) treated with either bevacizumab or a tyrosine kinase inhibitor in combination with chemotherapy at The Christie Hospital from January 2006 to September 2009. RESULTS:: Of 90 patients evaluated, 50 were eligible. Seventeen (34%), 4 (8%), and 3 (6%) patients developed Common Toxicity Criteria (v 3.0) grades 1, 2, and 3 HTN, respectively. Response rates were 42% for patients with grades 0 to 1 HTN compared with 86% for patients with ?grade 2 HTN (P=0.043). Median overall survival was 21.6 months for patients with grades 0 to 1 HTN and 25.2 months for patients with ?grade 2 HTN (P=0.270). Twelve patients (24%) developed grade 1 PTN and 4 patients (8%) developed ?grade 2 PTN. Median overall survival was 23.9 months for patients with grades 0 to 1 PTN and 4.2 months for those with ?grade 2 PTN (P=0.028). CONCLUSIONS:: To our knowledge, this is the first study to demonstrate the utility of PTN as a surrogate marker of outcome in antiangiogenic therapy for metastatic colorectal cancer. Although HTN is predictive of a significantly higher response rate, the development of PTN during treatment with bevacizumab or tyrosine kinase inhibitor portends poorer survival and should be evaluated prospectively. |
| Databáze: | OpenAIRE |
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