Toxicity associated with the long-term use of targeted therapies in patients with advanced renal cell carcinoma.
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.
Shepard
Dale R
DR
Department of Solid Tumor Oncology, Cleveland Clinic, Taussig Cancer Institute, 9500 Euclid Ave/R35, Cleveland, OH 44195, USA. shepard@ccf.org
Garcia
Jorge A
JA
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy*; D011494:Protein Kinases / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D000970:Antineoplastic Agents; D042461:Vascular Endothelial Growth Factor A; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases