Adjuvant and Neoadjuvant Small Molecule Targeted Therapy

Anil Kapoor



Non-localized renal cell carcinoma (RCC) carries a poor prognosis that imposes a serious risk of mortality upon patients. Traditionally, interleukin-2 and interferon-(alpha) were utilized in this setting with limited improvement in cancer-specific survival and high toxicity; however, newer agents such as Sunitinib, Sorafenib, Bevacizumab and Temsirolimous have demonstrated great potential and provide a new frontier in the management of high-risk RCC.

Methods and Methods

Pubmed and OVID Medline databases were queried for English articles from 1950 to December 2008 using the keywords “renal cell carcinoma” AND “high risk” and “renal cell carcinoma” AND “neoadjuvant”. Articles from these searches and the references of relevant articles were utilized. Articles published between 1996 and 2008 were included in this review. 


Risk stratification is imperative for optimal patient selection in adjuvant, neoadjuvant and research settings. Utilization of interferon-alpha 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.      


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 neoadjuvent therapy while minimizing toxicity in low-risk patients.  


Key words: renal cell carcinoma, adjuvant therapy, neoadjuvant therapy, neo-adjuvant, review

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ISSN: 1198-0052 (Print) ISSN: 1718-7729 (Online)