Non-clear cell (NCC) renal cell carcinoma (RCC) is less common and accounts for 25 % of all patients with metastatic RCC. Metastatic NCCRCC and clear cell (CC) RCC both respond infrequently to cytotoxic and cytokine therapy; however, compared with CCRCC patients, NCCRCC patients have a poorer prognosis. Tyrosine kinase inhibitors (TKIs) such as sorafenib and sunitinib have significant activity in metastatic NCCRCC, but the efficacy of each agent seems to vary between different NCCRCC forms. Preliminary clinical data for temsirolimus, one of the mammalian targets of rapamycin (mTOR) inhibitors, appear to be promising, but future phase III trials should include patients with RCCs with NCC histology as well as CCRCC, with appropriate stratification to take the balance between each treatment arm. Many ongoing phase II trials should provide interesting preliminary insights into the antitumor efficacy of particular agents in these tumors. These approaches will lead us to improvements in the management of NCCRCC so as we have already achieved with the more common CCRCC.
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