title: Management of metastatic renal cell carcinoma in the era of targeted therapies.
abstract: BACKGROUND
  Metastatic renal cell cancer is associated with poor prognosis and survival and is resistant to conventional chemotherapy. Therapeutic targeting of molecular pathways for tumour angiogenesis and other specific activation mechanisms offers improved tumour response and prolonged survival.
  
  
  OBJECTIVE
  To conduct a retrospective audit of metastatic renal cell carcinoma patients treated with targeted therapies.
  
  
  METHODS
  Data were extracted from clinical records of patients undergoing targeted treatment between 2005 and 2009 at two hospital sites. Data collected included pathology, systemic therapy class, toxicity and survival. Univariate and multivariate survival analyses were performed.
  
  
  RESULTS
  Sixty-one patients were treated with 102 lines of therapy with a median overall survival (OS) of 23 months, median time to failure of first-line treatment (TTF1) of 10 months and median time to failure of second-line treatment (TTF2) of 5.2 months. Time from first diagnosis to treatment >12 months was significantly associated with improved OS, longer TTF1, TTF2 and response to first-line anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (anti-VEGF TKI) therapy. Variables associated with tumour biology, natural history and the systemic inflammatory response were associated with improved OS and TTF1. Development of hypertension was predictive of anti-VEGF TKI outcome. Toxicities were as expected for each drug class.
  
  
  CONCLUSIONS
  Survival and toxicity outcomes from two Australian sites are comparable to published data. The adverse event profile differs to conventional chemotherapy. Clinicians caring for patients with metastatic renal cancer will need to become familiar with these toxicities and their management as these agents enter widespread use.
authors.affiliation: Department of Medical Oncology, Prince of Wales Hospital, University of New South Wales, Sydney, Australia. k.webber@unsw.edu.au
authors.forename: K
authors.initials: K
authors.lastname: Webber
authors.forename: A
authors.initials: A
authors.lastname: Cooper
authors.forename: H
authors.initials: H
authors.lastname: Kleiven
authors.forename: D
authors.initials: D
authors.lastname: Yip
authors.forename: D
authors.initials: D
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality; D002986:Clinical Trials as Topic / Q000379:methods; D019468:Disease Management; D016503:Drug Delivery Systems / Q000379:methods*; D005221:Fatigue / Q000139:chemically induced / Q000453:epidemiology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000453:epidemiology; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends
chemical_list: D000970:Antineoplastic Agents