Tyrosine-kinase inhibitors and bisphosphonates in the treatment of metastases from renal cell carcinoma

Bone metastases (BMs) are common in patients with renal cell carcinoma (RCC) and approximately in 30% of patients with metastatic RCC (mRCC) will develop. Inhibition of vascular endothelial growth factor (VEGF) has been pursued as a therapeutic target in the treatment of metastatic clear cell RCC (mRCC). Tyrosine kinase inhibitors (TKIs), such as sunitinib, pazopanib, sorafenib, and axitinib, became the therapy of choice for patients with mRCC. Apart from the undisputed effi cacy of TKI in treatment of mRCC, the problem of metastatic bone disease still remains. There is evidence that the presence of BMs in m-RCC patients has a signifi cant and clinically-relevant negative impact on survival and potentially on the outcome of VEGF-targeted therapy. Also, common practice in the treatment of such patients is bonedirected therapy with BPs. Recent evidence shows a potentially synergistic effect on effi cacy but also a potential impact on increased toxicity of combining TKIs and BPs. This review highlights the importance of this subject and aims to facilitate further research and optimize the treatment of this important and common group of RCC patients.