title: Optimizing treatment of metastatic renal cell carcinoma by changing mechanism of action.
abstract: Novel targeted agents, such as VEGF receptor-tyrosine kinase inhibitors (VEGFR-TKIs) and mTOR inhibitors, have improved therapy for metastatic renal cell carcinoma. Sequential administration of agents with similar mechanisms of action has shown some efficacy in small retrospective studies; however, prospective Phase II studies have reached differing conclusions, and there is a current lack of prospective randomized data to validate this approach. Sequential administration of agents with different mechanisms of action has shown clinical efficacy in prospective trials, including a randomized Phase III study (RECORD-1) of the mTOR inhibitor everolimus, the only targeted agent recommended for use after VEGFR-TKI failure in metastatic renal cell carcinoma. Ongoing research will further define the relative merits of other sequences in terms of clinical outcome.
authors.affiliation: Renal Cancer Unit, Department of Medicine, Royal Marsden Hospital, London SW3 6JJ, UK. james.larkin@rmh.nhs.uk
authors.forename: James
authors.initials: J
authors.lastname: Larkin
authors.forename: Charles
authors.initials: C
authors.lastname: Swanton
authors.forename: Lisa
authors.initials: L
authors.lastname: Pickering
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000473:pathology; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009362:Neoplasm Metastasis; D012189:Retrospective Studies