Evaluation of everolimus in renal cell cancer

The incidence of renal cell cancer (RCC) has been steadily increasing over the past decade. Advances in understanding the pathophysiology and carcinogenesis RCC have led to the development of novel therapies that target molecular pathways. Everolimus is a synthetic, orally available analogue of rapamycin that inhibits the activation of mTOR. Everolimus extended progression-free survival in RCC patients from 1.9 months (for patients receiving a placebo) to 4.9 months. Grades 3 and 4 adverse events include stomatitis, fatigue, pneumonitis, infections, asthenia, diarrhea, mucosal inflammation, dyspnea, rash, anorexia and dry skin. Grades 3 and 4 laboratory abnormalities include lymphopenia, anemia, thrombocytopenia, hyperglycemia, hypophosphatemia, hypercholesterolemia, hypertriglycemia, elevated creatinine, elevated alkaline phosphatase, elevated aspartate aminotransferase and elevated alanine aminotransferase. Studies have been conducted to evaluate any synergistic effect of combination therapies and continue to need to be further evaluated.

A systematic review of medical literature for everolimus as a single agent or combination was completed using PubMed.

Everolimus has significant clinical benefit and is well tolerated with reversible side effects as second- or third-line therapy for treating RCC. The next phase of research for everolimus is determining patient selection based on mTOR profile utilizing skills such as proteomics and genomics.