title: Second-line therapy for refractory renal-cell carcinoma.
abstract: In the last 5 years inhibitors of the VEGF/VEGFR and mTOR pathways have dramatically changed the therapeutic approach to metastatic renal cancer. Randomized controlled trials have shown that six targeted agents--sorafenib, sunitinib, temsirolimus, bevacizumab, everolimus and pazopanib--are able to improve patient outcome. Even if the choice of drug for first-line therapy is quite well defined, to date it is not easy to characterize and evaluate the efficacy of new therapies in second-line treatment. It is not clear whether, after first-line therapy with a VEGF/VEGFR inhibitor, use of mTOR or a second TKI inhibitor should be recommended. In this review we report on current evidence supporting the use of targeted agents in second-line therapy. Therefore we try to combine current clinical results with a practical clinical approach, with the goal of evaluating the best clinical decision for different clinical situations.
authors.affiliation: Istituto Oncologico Veneto, IRCCS, Padova, Italy. fable.zustovich@ioveneto.it
authors.forename: Fable
authors.initials: F
authors.lastname: Zustovich
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Lombardi
authors.forename: Ornella
authors.initials: O
authors.lastname: Nicoletto
authors.forename: Davide
authors.initials: D
authors.lastname: Pastorelli
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D000068258:Bevacizumab; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D058990:Molecular Targeted Therapy / Q000379:methods; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016207:Cytokines; D047428:Protein Kinase Inhibitors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases