title: Combination therapy of interleukin-2 and sorafenib improves survival benefits and prevents spontaneous pulmonary metastasis in murine renal cell carcinoma models.
abstract: OBJECTIVE
  The objective of this study was to evaluate the benefits of combination therapy consisting of recombinant human interleukin-2 and sorafenib for survival efficacy and the suppression of metastasis in murine renal cell carcinoma models.
  
  
  METHODS
  Lung-metastasized renal cell carcinoma mice were treated with various combinations of recombinant human interleukin-2 and sorafenib. Tumor growth was observed using a bioluminescence imaging system. Next, the nephrectomized renal cell carcinoma mice were administered various combinations of recombinant human interleukin-2 and sorafenib, followed by a lung resection in order to examine lung metastasis by bioluminescence imaging.
  
  
  RESULTS
  The increased life-span ratio in mice receiving combination therapy was 1.45, whereas that in mice treated with sorafenib or recombinant human interleukin-2 alone therapy was 1.28 and 1.07, respectively. The concomitant administration of recombinant human interleukin-2 and sorafenib had a metastasis-inhibitory effect, whereas the other treatments failed.
  
  
  CONCLUSIONS
  These findings indicate that combination therapy of recombinant human interleukin-2 and sorafenib may offer better outcomes than either monotherapy with recombinant human interleukin-2 or sorafenib with respect to survival benefits and the prevention of pulmonary metastasis in renal cell carcinoma patients.
authors.affiliation: Discovery Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Amagai
authors.forename: Mitsunobu
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Kanji
authors.initials: K
authors.lastname: Hojo
authors.forename: Motofumi
authors.initials: M
authors.lastname: Iguchi
authors.forename: Tooru
authors.initials: T
authors.lastname: Wada
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ide
authors.forename: Akira
authors.initials: A
authors.lastname: Kato
authors.forename: Michitaka
authors.initials: M
authors.lastname: Shichijo
authors.forename: Kenji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000008:administration & dosage*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D045744:Cell Line, Tumor; D005260:Female; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D008175:Lung Neoplasms / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D009392:Nephrectomy; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D000077157:Sorafenib; D015996:Survival Rate
chemical_list: D001557:Benzenesulfonates; D007376:Interleukin-2; D010671:Phenylurea Compounds; D011725:Pyridines; D011994:Recombinant Proteins; D009536:Niacinamide; D000077157:Sorafenib