title: Tolerability of first-line therapy for metastatic renal cell carcinoma.
abstract: The treatment options for metastatic renal cell carcinoma have expanded rapidly over the past 3 years, with four new agents available and others in late-stage development. This has resulted in a change of the standard of first-line care, with sunitinib or bevacizumab plus interferon the treatments of choice for patients with good or intermediate-risk renal cell carcinoma and temsirolimus treatment of choice for poor-risk disease. Sunitinib and bevacizumab plus interferon have similar efficacy, meaning that treatment choice is influenced by other factors: disease-related factors such as clear cell versus non-clear cell histology; patient factors such as co-morbidities, Memorial Sloan-Kettering Cancer Center risk and patient preference; and drug-related factors such as tolerability profile. The aim of this review is to describe the tolerability of the first-line treatment options for clear cell renal cell carcinoma, giving consideration to how tolerability profiles relate to drug mechanism of action. Thus, the incidence and aetiology of side effects related to vascular endothelial growth factor and vascular endothelial growth factor receptor inhibition using sunitinib and bevacizumab, as well as those of the non-specific side effects observed with sunitinib, are described. In addition, the potential patient impact and management of these side effects, as well as those of interferon and temsirolimus, are considered. Finally, the implications of the tolerability profiles of these agents for combination therapy and use in broader populations than those enrolled in trials are assessed.
authors.affiliation: Medical Oncology, IRCCS San Matteo University Hospital Foundation, Piazzale C. Golgi 19, I-27100 Pavia, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Porta
authors.forename: Cezary
authors.initials: C
authors.lastname: Szczylik
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D000068258:Bevacizumab; D001778:Blood Coagulation Disorders / Q000139:chemically induced; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D002318:Cardiovascular Diseases / Q000139:chemically induced; D017326:Clinical Trials, Phase III as Topic / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D007372:Interferons / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077210:Sunitinib; D014945:Wound Healing / Q000187:drug effects
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D007211:Indoles; D009363:Neoplasm Proteins; D011758:Pyrroles; D000068258:Bevacizumab; C401859:temsirolimus; D007372:Interferons; D040262:Receptors, Vascular Endothelial Growth Factor; D000077210:Sunitinib; D020123:Sirolimus