title: Efficacy of sequential treatment with sunitinib-everolimus in an orthotopic mouse model of renal cell carcinoma.
abstract: OBJECTIVE
  Sequential treatment with targeted agents is standard of care for patients with metastatic renal cell carcinoma (mRCC). However, clinical data directly comparing treatment outcomes with a mammalian target of rapamycin inhibitor or a vascular endothelial growth factor-targeted agent in the second-line setting are lacking. We evaluated sequential treatment in a syngeneic, orthotopic mouse model of mRCC.
  
  
  METHODS
  BALB/c mice were orthotopically implanted with murine RCC (RENCA) cells expressing luciferase and randomized to vehicle, sunitinib, sunitinib followed by sorafenib, or sunitinib followed by everolimus. Tumor growth and metastases were assessed by in vivo (whole body) and ex vivo (primary tumor, lung, liver) luciferase activity and necropsies, performed on day 20 or 46 for vehicle and treatment groups, respectively.
  
  
  RESULTS
  Sunitinib followed by everolimus was associated with reduced luciferase activity and primary tumor weight and volume compared with sunitinib, and sunitinib followed by sorafenib.
  
  
  CONCLUSIONS
  Sequential therapy with sunitinib followed by everolimus demonstrated significant antitumor and anti-metastatic effects.
authors: Department of Medicine, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. james.larkin@rmh.nhs.uk
authors: James
authors: J
authors: Larkin
authors: Norbert
authors: N
authors: Esser
authors: Emiliano
authors: E
authors: Calvo
authors: Zenta
authors: Z
authors: Tsuchihashi
authors: Ulrike
authors: U
authors: Fiedler
authors: Ralph
authors: R
authors: Graeser
authors: Dennis
authors: D
authors: Kim
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000494:pharmacology*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D000068338:Everolimus; D005260:Female; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects; D011897:Random Allocation; D020123:Sirolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077210:Sunitinib
chemical_list: D007211:Indoles; D011758:Pyrroles; D000068338:Everolimus; D008156:Luciferases; D000077210:Sunitinib; D020123:Sirolimus