Adjuvant and Neoadjuvant Small Molecule Targeted Therapy

BACKGROUND: Non-localized renal cell carcinoma (rcc) carries a poor prognosis with a significant risk of mortality for patients. Traditionally, interleukin-2 and interferon alfa have been administered in this setting, with high toxicity and limited improvement in cancer-specific survival. However, newer agents such as sunitinib, sorafenib, bevacizumab, and temsirolimus have demonstrated great potential and provide a new frontier in the management of high-risk rcc. METHODS: We queried PubMed and the Medline OVID databases for English articles from 1950 to December 2008 using the keywords "renal cell carcinoma," "high risk" and "renal cell carcinoma," and "neoadjuvant." Articles from these searches and the reference lists of relevant articles were obtained. Articles published between 1996 and 2008 were included in the present review. RESULTS: Risk stratification is imperative for optimal patient selection in adjuvant, neoadjuvant, and research settings. Utilization of interferon alfa and interleukin-2 has not demonstrated improved disease-free survival in the adjuvant setting. A number of adjuvant vaccines have also failed to demonstrate improved survival. The adjuvant role of targeted small-molecule inhibitors such as sorafenib, sunitinib, and temsirolimus is currently under investigation in phase iii trials. Sporadic case reports have demonstrated promising results with neoadjuvant use of these agents, and a pilot study of neoadjuvant temsirolimus is currently underway at our centre. CONCLUSIONS: The role, efficacy, and toxicity of adjuvant and neoadjuvant targeted small-molecule inhibitors in high-risk rcc remains to be delineated. Ideally, clinicians will be able to identify high-risk patients and offer treatment to those who would benefit most from adjuvant and neoadjuvant therapy, while minimizing toxicity in low-risk patients.