Abstract
The recent advances in identification of the molecular mechanisms related to tumorigenesis and angiogenesis, along with the understanding of molecular alterations involved in renal cell carcinoma (RCC) pathogenesis, has allowed the development of several new drugs which have revolutionized the treatment of metastatic renal cell carcinoma (mRCC).This process has resulted in clinically significant improvements in median overall survival and an increasing number of patients undergoes two or even three lines of therapy. Therefore, it is necessary a long-term perspective of the treatment: planning a sequential and personalized therapeutic strategy to improve clinical outcome, the potential to achieve long-term response, and to preserve quality of life (QOL), minimizing treatment-related toxicity and transforming mRCC into a chronically treatable condition.Because of the challenges still encountered to draw an optimal therapeutic sequence, the main focus of this article will be to propose the optimal sequencing of existing, approved, oral targeted agents for the treatment of mRCC using evidence-based data along with the knowledge available on the tumor behavior and mechanisms of resistance to anti-angiogenic treatment to provide complementary information and to help the clinicians to maximize the effectiveness of targeted agents in the treatment of mRCC.
Highlights
Renal cell carcinoma (RCC) has seen in last years a rapid and continuous increase of new cases [1]
The recent advances in identification of the molecular mechanisms related to tumorigenesis, angiogenesis, cell growth and proliferation, along with the understanding of molecular alterations involved in RCC pathogenesis [7,8,9,10,11,12], allowed to identify targets of clinical interest: the vascular endothelial growth factor (VEGF) and its receptors (VEGFr), the mammalian target of rapamycin signaling pathway, the fibroblast growth factor (FGF) and its receptor (FGFr), the hypoxiainducible factors (HIFs) and Akt activation
At 22 weeks, patients completed a questionnaire assessing their preferences: significantly more patients preferred Pazopanib (70%) over Sunitinib (22%); 8% did not prefer any agent [36]. These findings have shown Sunitinib and Pazopanib are agents with similar efficacy in first-line treatment, but the use of Pazopanib as first line therapy, in patient with good-intermediate risk metastatic renal cell carcinoma (mRCC), seems more convenient for his better safety profile
Summary
Renal cell carcinoma (RCC) has seen in last years a rapid and continuous increase of new cases [1]. The AXIS trial is a phase III RCT study comparing axitinib and sorafenib as second line treatment in patients with advanced clear cell RCC, after a prior systemic regimen including sunitinib (54%), cytokines (35%), bevacizumab (8%) or temsirolimus (3%).
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