Systemic treatment options for advanced renal cell carcinoma (RCC) have expanded considerably with the development of targeted therapies. Clear cell RCC commonly features mutation or inactivation of the von Hippel-Lindau gene and resultant overexpression of vascular endothelial growth factor (VEGF). The first drug to validate VEGF as a target in the treatment of clear cell RCC was the monoclonal antibody bevacizumab. Since then, anti-VEGF receptor therapy with multitargeted kinase inhibitors also has shown substantial efficacy. Sunitinib is now a standard first-line therapy for advanced disease and sorafenib is among the second-line treatment options. Other kinase inhibitors are in development. Mammalian target of rapamycin (mTOR) is a second validated therapeutic target as the mTOR inhibitor temsirolimus has been shown to prolong survival in first-line treatment of poor prognosis RCC of all histologies. Everolimus is an oral mTOR inhibitor and has been shown to prolong progression-free survival when used in second-line treatment. Non-clear cell and sarcomatoid RCC are both underrepresented in completed trials but are the subject of active research. Ongoing and planned studies will also evaluate the use of combinations of targeted agents, a strategy that is not advisable outside of clinical trials. Finally, postnephrectomy adjuvant treatment with targeted agents is not yet standard but is under investigation in phase III trials.
Philip J. Saylor and M. Dror Michaelson
Philip J. Saylor and Matthew R. Smith
Androgen deprivation therapy (ADT) plays a central role in the management of men with locally advanced, recurrent, and metastatic prostate cancer. Because most men diagnosed with prostate cancer will die of something other than their cancer, treatment-related adverse effects are highly relevant to their long-term health. Benefits of ADT in each clinical setting must be weighed against ADT-related adverse effects. ADT is detrimental to several metabolic end points and to bone health. ADT has been prospectively shown to cause decreased lean muscle mass, increased fat mass, weight gain, increased cholesterol and triglycerides, insulin resistance, and loss of bone mineral density. In population-based analyses it has been associated with an increased incidence of diabetes, clinical fractures, and cardiovascular disease. Data-driven recommendations for managing these adverse effects are needed. Currently the authors advocate the use of adapted practice guidelines developed to prevent diabetes, fractures, and coronary heart disease in the general population.