Exploring the role of novel agents in the treatment of renal cell carcinoma.
ABSTRACT Renal cell carcinoma represents nearly 3% of all cancers, predominantly affecting individuals >or=50 years of age, and until recently, few treatments options were available for metastatic disease. The 5-year median survival for these patients with metastatic renal cell carcinoma has been estimated at <10%. This review explores the data of the most relevant trials focusing on new approaches with novel agents, including sunitinib, sorafenib, bevacizumab, temsirolimus, as well as their combinations with traditional agents. We describe mechanisms of action, activity, and toxicity profile of those agents, as well as administration schedules that have been studied in clinical trials.
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ABSTRACT: ContextFew treatment options were available for metastatic renal cell carcinoma (mRCC) until the development of novel targeted agents directed against angiogenesis and tumour growth.European Urology Supplements 11/2009; 8(10):809-814. · 3.37 Impact Factor
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ABSTRACT: Sunitinib is an inhibitor of tyrosine-kinase receptors, and no biomarker predictive of sunitinib response is available. The purpose of this preclinical study was to show whether sunitinib molecular targets could be used as biomarkers to assess tumor response to sunitinib in human cancer cell line xenografts of three different tumor types. Using mice xenografted with liver, breast and renal carcinoma cell lines, we sequentially analyzed the effect of 7-day sunitinib treatment on tumor and vascular compartments. In all xenografts, microvessel damage occurred from Day 1. Tumor damage also occurred in liver, breast, but not in renal xenografts. Using specific human and mouse probes for genes encoding sunitinib targets, we showed a significant relation between apoptotic tumor cell numbers and human PDGFRΒ and RET mRNA expression in liver cancer and to human VEGFR2 expression in breast cancer xenografts. In contrast, in renal cancer xenografts, vascular effect evaluated by measuring endothelial cell apoptosis was related to mouse Vegfr1, Vegfr2 and Vegfa-164 expression. This study identifies sunitinib vascular and tumor effects according to different tumor types and shows that sunitinib molecular targets used as biomarkers enable assessment of therapeutic response.Cancer Chemotherapy and Pharmacology 09/2013; · 2.80 Impact Factor
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ABSTRACT: Optimal long-lasting treatment with sunitinib and sorafenib is limited by dose modifications (DMs) due to adverse events (AEs). These AEs may be underrecognized and their influence on health-related quality of life (HRQL) underestimated. Improved insight into the relationship between AEs and therapy decisions is needed. To improve decision making around managing symptoms and reduce DMs, this study was set up to explore the influence of patient-reported symptoms on therapy decisions. In this multicenter cohort study, patient characteristics, reasons for and different forms of used dose modifications, and AEs were prospectively obtained from cancer patients on sunitinib/sorafenib treatment. Used instruments to get insight into AEs were the patient-scored Utrecht Symptom Diary (USD) and the professional-scored Common Terminology Criteria for AEs version 3.0. Median total treatment duration in 42 patients was 16 weeks. Median time till dose modification was 10 weeks. DMs occurred mostly due to multiple mild AEs. By using the USD, a higher prevalence of most AEs was found compared to the literature. Sixty percent of the patients experienced a decreased HRQL due to multiple AEs. Because severe AEs due to sunitinib/sorafenib treatment seldom occur, it is more important to focus on treating and preventing multiple mild AEs with higher impact on HRQL, when trying to avoid dose modifications. Using patient self-reported measurement methods helps to early recognize symptoms and to differentiate among symptom intensities. This systematic approach might help to achieve the optimal dosing, which might improve PFS and OS.Supportive Care in Cancer 04/2014; · 2.09 Impact Factor