Exploring the role of novel agents in the treatment of renal cell carcinoma

Oncology Center, Sirio Libanês Hospital, São Paulo, Brazil.
Cancer Treatment Reviews (Impact Factor: 7.59). 10/2008; 34(8):750-60. DOI: 10.1016/j.ctrv.2008.07.002
Source: PubMed


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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    • "Current treatment approaches utilising novel targeted agents At present, treatment for mRCC with molecularly targeted agents can be broadly divided into the following categories: previously untreated patients, those refractory to immunotherapy or chemotherapy, and those who have failed treatment with VEGF-targeted therapy [9]. An important consideration that influences treatment decisions is the Memorial Sloan-Kettering Cancer Centre (MSKCC) prognostic risk stratification system, which is widely used to define patient profiles and provide an indication of overall survival (OS) [10] [11] [12]. "
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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.
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    ABSTRACT: The outcome prediction for renal cell cancer (RCC) remains controversial, and although many parameters have been tested for prognostic significance, only a few have achieved widespread acceptance in clinical practice. The TNM staging system defines local extension of the primary tumour (T), involvement of regional lymph nodes (N), and presence of distant metastases (M). This review focuses on reassessing the current TNM staging system for RCC. A literature search in English was performed using the National Library of Medicine database and the following keywords: renal cell cancer, kidney neoplasm, and staging. We scrutinized 1952 references, and 62 were selected for review based on their pertinence, study size, and overall contribution to the field. The prognostic significance of tumour size for localized RCC has been investigated in a large number of studies. As a consequence, many modifications of the TNM staging system were primarily made to the size cut points between stage I and II tumours. The latest three revisions of the TNM system are systematically reviewed. For the heterogeneous group of locally advanced RCCs, involving different anatomic structures surrounding the kidney, the situation is still the subject of controversial scientific dispute. In detail, perirenal fat invasion, direct infiltration of the ipsilateral adrenal gland, invasion of the urinary collecting system, infiltration of renal sinus fat, and vena cava and renal vein thrombosis are disputed. Finally, staging of lymph node metastases and distant metastatic disease is discussed. Special emphasis should be put on renal sinus invasion for stage evaluation. Retrospective studies relying on material collected at a time when no emphasis was placed on adequate sampling of the renal sinus should be treated with caution. In view of new treatment opportunities, the current TNM staging system of RCC and any other staging system must be dynamic.
    European Urology 08/2009; 56(4):636-43. DOI:10.1016/j.eururo.2009.06.036 · 13.94 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.
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