REVIEW ARTICLEBisphosphonates and vascular endothelial growth factor-targeted drugs in the treatment of patients with renal cell carcinoma metastatic to boneVrdoljak, Eduard; Rini, Brian; Schmidinger, Manuela; Omrčen, Tomislav; Torday, Laszlo; Szczylik, Cezary; Sella, AvishayAuthor Information aMedical School Split, University Hospital Split, Center of Oncology, Split, Croatia bDepartment of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, Ohio, USA cDepartment of Medicine I, Clinical Division of Oncology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria dDepartment of Oncotherapy, University of Szeged, Szeged, Hungary eDepartment of Oncology, Military Medical Institute, Warsaw, Poland fDepartment of Oncology, Assaf Harofeh Medical Center, Tel Aviv, Israel Correspondence to Eduard Vrdoljak, MD, PhD, Center of Oncology, Medical School Split, University Hospital Split, Spinciceva 1, 21000 Split, Croatia Tel: +385 21 556 129; fax: +385 21 556 461; e-mail: email@example.com Received December 20, 2012 Accepted February 14, 2013 Anti-Cancer Drugs: June 2013 - Volume 24 - Issue 5 - p 431-440 doi: 10.1097/CAD.0b013e328360335f Buy Metrics Abstract Skeletal involvement is common in patients with renal cell carcinoma (RCC): ∼30% of patients with metastatic RCC (mRCC) will develop bone metastases. Inhibition of vascular endothelial growth factor (VEGF) has been pursued as a therapeutic target in the treatment of metastatic clear-cell RCC (m-ccRCC). Tyrosine kinase inhibitors (TKIs), such as sunitinib, pazopanib, sorafenib, and the monoclonal antibody bevacizumab, became the therapy of choice for patients with m-ccRCC. Besides the undisputed efficacy of TKI in the treatment of m-ccRCC, the problem of metastatic bone disease still remains. There is evidence that the presence of bone metastases in m-ccRCC patients has a significant and clinically relevant negative impact on survival and potentially on the outcome of VEGF-targeted therapy. Also, a relatively common practice in the treatment of such patients is bone-directed therapy with bisphosphonates (BPs). Recent evidence shows a potentially synergistic effect on efficacy but also the potential for increased toxicity of combining TKIs and BPs. This review article 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. Copyright © 2013 Wolters Kluwer Health, Inc. All rights reserved.