Publications (5)11.17 Total impact
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Article: Sequential treatment with sorafenib and sunitinib in metastatic renal cell carcinoma: clinical outcomes from a retrospective clinical study.
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ABSTRACT: Sorafenib and sunitinib are inhibitors of receptor protein tyrosine kinases (TKIs) and are approved for the treatment of metastatic renal cell carcinoma (mRCC). Although the mTOR inhibitor everolimus is effective for the treatment of patients who have failed TKI therapy, it is important to consider all available treatment options before switching therapy mode of action. Herein, we report outcomes in patients with mRCC switched to sorafenib following disease progression on sunitinib treatment. The medical records of 35 patients treated between November 2006 and November 2009 at two large referral centers in Greece were retrospectively analyzed for time-to-progression (TTP), overall survival (OS), and tolerability of sorafenib after sunitinib. Median TTP and OS on sorafenib were 4.9 and 11.5 months, respectively. Among 33 patients evaluable for tumor response, three had a partial response and 17 achieved disease stabilization (objective response rate 8.5%; total clinical benefit rate 57%). Sorafenib was well tolerated, with mostly grade 1/2 adverse events and no treatment-related deaths. Sorafenib was effective and well tolerated in this group of patients. The TTP with sorafenib following sunitinib was comparable to outcomes reported previously, providing further support that TKIs should be used in sequence before switching to an mTOR inhibitor.Medical Oncology 01/2011; 29(2):750-4. · 2.14 Impact Factor -
Article: Prognostic stratification of patients with advanced renal cell carcinoma treated with sunitinib: comparison with the Memorial Sloan-Kettering prognostic factors model.
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ABSTRACT: The treatment paradigm in advanced renal cell carcinoma (RCC) has changed in the recent years. Sunitinib has been established as a new standard for first-line therapy. We studied the prognostic significance of baseline characteristics and we compared the risk stratification with the established Memorial Sloan Kettering Cancer Center (MSKCC) model. This is a retrospective analysis of patients treated in six Greek Oncology Units of HECOG. Inclusion criteria were: advanced renal cell carcinoma not amenable to surgery and treatment with Sunitinib. Previous cytokine therapy but no targeted agents were allowed. Overall survival (OS) was the major end point. Significance of prognostic factors was evaluated with multivariate cox regression analysis. A model was developed to stratify patients according to risk. One hundred and nine patients were included. Median follow up has been 15.8 months and median OS 17.1 months (95% CI: 13.7-20.6). Time from diagnosis to the start of Sunitinib (<or= 12 months vs. >12 months, p = 0.001), number of metastatic sites (1 vs. >1, p = 0.003) and performance status (PS) (<or= 1 vs >1, p = 0.001) were independently associated with OS. Stratification in two risk groups ("low" risk: 0 or 1 risk factors; "high" risk: 2 or 3 risk factors) resulted in distinctly different OS (median not reached [NR] vs. 10.8 [95% confidence interval (CI): 8.3-13.3], p < 0.001). The application of the MSKCC risk criteria resulted in stratification into 3 groups (low and intermediate and poor risk) with distinctly different prognosis underlying its validity. Nevertheless, MSKCC model did not show an improved prognostic performance over the model developed by this analysis. Studies on risk stratification of patients with advanced RCC treated with targeted therapies are warranted. Our results suggest that a simpler than the MSKCC model can be developed. Such models should be further validated.BMC Cancer 02/2010; 10:45. · 3.01 Impact Factor -
Article: Brain natriuretic peptide precursor (NT-pro-BNP) levels predict for clinical benefit to sunitinib treatment in patients with metastatic renal cell carcinoma.
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ABSTRACT: 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. 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. 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). 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.BMC Cancer 01/2010; 10:489. · 3.01 Impact Factor -
Article: Sunitinib treatment for patients with clear-cell metastatic renal cell carcinoma: clinical outcomes and plasma angiogenesis markers.
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ABSTRACT: Sunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDGFR. It has been approved for the treatment of metastatic renal-cell carcinoma and gastrointestinal stromal tumors. Although it has been shown to prolong disease-free and overall survival in renal-cell carcinoma patients, only 70% of the treated population receive a clinical benefit (CB) from the treatment. Markers that could predict clinical benefit to sunitinib would be an important aid in monitoring and following their treatment. We assessed the outcome and plasma proangiogenic factors in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib in our institution. We have treated 42 patients with metastatic clear-cell renal carcinoma with sunitinib. Plasma concentrations of VEGF-A, sVEGFR2 and PDGF were determined by ELISA. At the time of analysis 39 patients were evaluable for response and 30 patients had obtained a clinical benefit (CB). Median progression-free survival was 268 days (8.93 months) and median overall survival was 487 days (16.23 months). Interestingly, disease stabilization or objective response resulted in comparable overall survival. Most treatment-related adverse events were of mild-to-moderate intensity with one treatment-related death. Plasma sVEGFR2 and PDGF levels had no predictive value. Fold-increase in plasma VEGF was significantly lower in patients that obtained a CB as compared to patients that progressed after two cycles of treatment. Plasma VEGF did not increase in patients with initial CB at the time of progression. Sunitinib showed substantial activity in mRCC. Disease stabilization or objective response resulted in comparable overall survival and both outcomes should be considered positive. Fold-increase in plasma VEGF predicts for CB and could be a candidate marker. Progression after initial CB is not associated with elevated plasma VEGF, implying a different mechanism of resistance.BMC Cancer 02/2009; 9:82. · 3.01 Impact Factor -
Article: Sunitinib treatment for patients with clear-cell metastatic renal cell carcinoma: clinical outcomes and plasma angiogenesis markers
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ABSTRACT: Abstract Background Sunitinib is a protein tyrosine kinase-inhibitor targeting VEGFR, c-kit and PDGFR. It has been approved for the treatment of metastatic renal-cell carcinoma and gastrointestinal stromal tumors. Although it has been shown to prolong disease-free and overall survival in renal-cell carcinoma patients, only 70% of the treated population receive a clinical benefit (CB) from the treatment. Markers that could predict clinical benefit to sunitinib would be an important aid in monitoring and following their treatment. We assessed the outcome and plasma proangiogenic factors in patients with metastatic renal cell carcinoma (mRCC) treated with sunitinib in our institution. Methods We have treated 42 patients with metastatic clear-cell renal carcinoma with sunitinib. Plasma concentrations of VEGF-A, sVEGFR2 and PDGF were determined by ELISA. Results At the time of analysis 39 patients were evaluable for response and 30 patients had obtained a clinical benefit (CB). Median progression-free survival was 268 days (8.93 months) and median overall survival was 487 days (16.23 months). Interestingly, disease stabilization or objective response resulted in comparable overall survival. Most treatment-related adverse events were of mild-to-moderate intensity with one treatment-related death. Plasma sVEGFR2 and PDGF levels had no predictive value. Fold-increase in plasma VEGF was significantly lower in patients that obtained a CB as compared to patients that progressed after two cycles of treatment. Plasma VEGF did not increase in patients with initial CB at the time of progression. Conclusion Sunitinib showed substantial activity in mRCC. Disease stabilization or objective response resulted in comparable overall survival and both outcomes should be considered positive. Fold-increase in plasma VEGF predicts for CB and could be a candidate marker. Progression after initial CB is not associated with elevated plasma VEGF, implying a different mechanism of resistance.BMC Cancer. 01/2009;
