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Open Access Highly Accessed Research article

Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma

Konstantinos T Papazisis12*, Lukas F Kontovinis12, Christos N Papandreou3, George Kouvatseas4, Christos Lafaras5, Evangelos Antonakis6, Maria Christopoulou6, Charalambos Andreadis1, Despoina Mouratidou1 and Alexandros H Kortsaris7

Author Affiliations

1 3rd Department of Medical Oncology, Theagenion Cancer Hospital, Al. Simeonidi str. 2, 54007, Thessaloniki, Greece

2 Applied Molecular Oncology Laboratory, Theagenion Cancer Hospital, Al. Simeonidi str. 2, 54007, Thessaloniki, Greece

3 Department of Medical Oncology, University Hospital of Larissa, Biopolis 41110, Larissa, Greece

4 Health Data Specialists Ltd, 11526, Athens, Greece

5 Cardiology Unit, Theagenion Cancer Hospital, Al. Simeonidi str. 2, 54007, Thessaloniki, Greece

6 Laboratory of Biochemistry, Theagenion Cancer Hospital, Al. Simeonidi str. 2, 54007, Thessaloniki, Greece

7 Laboratory of Biochemistry, Department of Medicine, Democritus University of Thrace, Alexandroupolis, Greece

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BMC Cancer 2010, 10:489  doi:10.1186/1471-2407-10-489

Published: 14 September 2010

Abstract

Background

Sunitinib is an oral, multitargeted tyrosine kinase inhibitor that has been approved for the treatment of metastatic renal cell carcinoma. Although the majority of sunitinib-treated patients receive a clinical benefit, almost a third of the patients will not respond. Currently there is no available marker that can predict for response in these patients.

Methods

We estimated the plasma levels of NT-pro-BNP (the N-terminal precursor of brain natriuretic peptide) in 36 patients that were treated with sunitinib for metastatic clear-cell renal carcinoma.

Results

From the 36 patients, 9 had progressive disease and 27 obtained a clinical benefit (objective response or disease stabilization). Increases in plasma NT-pro-BNP were strongly correlated to clinical outcome. Patients with disease progression increased plasma BNP at statistically significant higher levels than patients that obtained a clinical benefit, and this was evident from the first 15 days of treatment (a three-fold increase in patients with progressive disease compared to stable NT-pro-BNP levels in patients with clinical benefit, p < 0.0001). Median progression-free survival was 12.0 months in patients with less than 1.5 fold increases (n = 22) and 3.9 months in patients with more than 1.5 fold increases in plasma NT-pro-BNP (n = 13) (log-rank test, p = 0.001).

Conclusions

This is the first time that a potential "surrogate marker" has been reported with such a clear correlation to clinical benefit at an early time of treatment. Due to the relative small number of accessed patients, this observation needs to be further addressed on larger cohorts. More analyses, including multivariate analyses are needed before such an observation can be used in clinical practice.