title: Targeted therapies for renal cell carcinoma: review of adverse event management strategies.
abstract: With the advent of targeted agents for the treatment of renal cell carcinoma (RCC), overall survival has improved, and patients are being treated continuously for increasingly long periods of time. This has raised challenges in the management of adverse events (AEs) associated with the six targeted agents approved in RCC-sorafenib, sunitinib, pazopanib, bevacizumab (in combination with interferon alpha), temsirolimus, and everolimus. Suggestions for monitoring and managing AEs have been published, but there are few consensus recommendations. In addition, there is a risk that patients will be subjected to multiple unnecessary investigations. In this review, we aimed to identify the level of supporting evidence for suggested AE management strategies to provide practical guidance on essential monitoring and management that should be undertaken when using targeted agents. Five databases were systematically searched for relevant English language articles (including American Society of Clinical Oncology abstracts) published between January 2007 and March 2011; European Society of Medical Oncology congress abstracts were hand searched. Strategies for AE management were summarized and categorized according to the level of recommendation. A total of 107 articles were identified that describe a large number of different investigations for monitoring AEs and interventions for AE management. We identify and summarize clear recommendations for the management of dermatologic, gastrointestinal, thyroid, cardiovascular, and other AEs, based predominantly on expert opinion. However, because the evidence for the suggested management strategies is largely anecdotal, there is a need for further systematic investigation of management strategies for AEs related to targeted therapies for RCC.
authors.affiliation: Cambridge University Health Partners, Cambridge, UK. tim.eisen@medschl.cam.ac.uk
authors.forename: Tim
authors.initials: T
authors.lastname: Eisen
authors.forename: Cora N
authors.initials: CN
authors.lastname: Sternberg
authors.forename: Caroline
authors.initials: C
authors.lastname: Robert
authors.forename: Peter
authors.initials: P
authors.lastname: Mulders
authors.forename: Lynda
authors.initials: L
authors.lastname: Pyle
authors.forename: Stephan
authors.initials: S
authors.lastname: Zbinden
authors.forename: Hassan
authors.initials: H
authors.lastname: Izzedine
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
mesh_terms: D000855:Anorexia / Q000139:chemically induced / Q000628:therapy; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D001557:Benzenesulfonates / Q000009:adverse effects; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism*; D002319:Cardiovascular System / Q000187:drug effects; D003875:Drug Eruptions / Q000628:therapy; D005060:Europe; D000068338:Everolimus; D019317:Evidence-Based Medicine; D041981:Gastrointestinal Tract / Q000187:drug effects; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced / Q000628:therapy; D007191:Indazoles; D007211:Indoles / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D058990:Molecular Targeted Therapy / Q000379:methods; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011014:Pneumonia / Q000139:chemically induced / Q000628:therapy; D047428:Protein Kinase Inhibitors / Q000009:adverse effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011725:Pyridines / Q000009:adverse effects; D011743:Pyrimidines / Q000009:adverse effects; D011758:Pyrroles / Q000009:adverse effects; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives; D000077157:Sorafenib; D013449:Sulfonamides / Q000009:adverse effects; D000077210:Sunitinib; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D015431:Weight Loss / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; D000068258:Bevacizumab; C401859:temsirolimus; C516667:pazopanib; D000068338:Everolimus; D000077157:Sorafenib; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases; D000077210:Sunitinib; D020123:Sirolimus