Toxicity associated with the long-term use of targeted therapies in patients with advanced renal cell carcinoma

Abstract

VEGF and mTOR inhibitors have encouraging clinical activity for patients with advanced renal cell carcinoma (RCC), but may lead to significant short- and long-term toxicities. Although 40–70% of adverse events (AEs) are grade 1 and 2, 10–20% of patients develop grade 3 or 4 AEs requiring dose reductions, drug holidays or treatment discontinuation. The long-term impact of the most common grade 3 and 4 AEs observed in Phase III trials evaluating VEGF and mTOR inhibitors, including hypertension, decreased left ventricular ejection fraction, hand–foot-syndrome and myelosuppression, are a concern in RCC patients who are living longer and receiving chronic sequential or combination therapy. There is a clear need to develop a more rational way to individualize therapy for RCC. Long-term follow-up from existing Phase II/III trials should provide us with increased understanding of the potential implications of AEs in RCC patients. Prevention, early recognition and aggressive management of side effects are fundamental to avoid significant long-term complications and unnecessary dose reductions, which can ultimately reduce the efficacy of these novel agents.

Keywords::

• bevacizumab
• renal cell carcinoma
• sorafenib
• sunitinib
• targeted therapy
• temsirolimus
• toxicity

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.