Locally Advanced or Metastatic Non-clear Cell Type Renal Cell Carcinoma Clinical Trial
Recent advances in understanding the biology and genetics of renal cell carcinoma (RCC) have
led to major therapeutic implications. Von Hippel-Lindau (VHL) gene inactivation, present in
the majority of sporadic forms of RCC, leads to a defective VHL protein, followed by an
active transcription of hypoxia-inducible genes, including vascular endothelial growth
factor (VEGF), platelet-derived growth factor (PDGF), c-kit, and others. However, the
concept of VHL inactivation in RCC and the subsequent malignant phenotype is almost
exclusively seen in patients with clear cell histology.
The data about efficacy of VEGF receptor inhibitors for non-clear cell RCC (NCRCC) is rare
until now. Recently, however, sunitinib and sorafenib showed its worth for NCRCC in extended
access programs.1-3 Although it is not certain, the underlying mechanism of their action
might lie in that papillary, chromophobe, and sarcomatoid type overexpress c-kit, which is
also a target of both drugs and could therefore provide a therapeutic target for non-clear
cell subtypes.4-7 Pazopanib is also a potent and selective, orally available, small molecule
inhibitor of VEGFR-1,-2, and -3, PDGF-α, PDGF-β, and c-kit tyrosine kinases. It has been
validated and licensed for advanced clear cell RCC (CCRCC).8 However, there is very few data
about its efficacy for NCRCC.
In this study, we try to evaluate the efficacy of pazopanib in metastatic NCRCC.
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