Combination therapy of interleukin-2 and sorafenib improves survival benefits and prevents spontaneous pulmonary metastasis in murine renal cell carcinoma models

Jpn J Clin Oncol. 2010 Jun;40(6):503-7. doi: 10.1093/jjco/hyp200. Epub 2010 Jan 27.

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.

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzenesulfonates / administration & dosage*
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / secondary*
  • Carcinoma, Renal Cell / surgery
  • Cell Line, Tumor
  • Female
  • Interleukin-2 / administration & dosage*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology*
  • Kidney Neoplasms / surgery
  • Lung Neoplasms / mortality
  • Lung Neoplasms / prevention & control*
  • Lung Neoplasms / secondary*
  • Mice
  • Mice, Inbred BALB C
  • Nephrectomy
  • Niacinamide / analogs & derivatives
  • Phenylurea Compounds
  • Pyridines / administration & dosage*
  • Recombinant Proteins / administration & dosage
  • Sorafenib
  • Survival Rate

Substances

  • Benzenesulfonates
  • Interleukin-2
  • Phenylurea Compounds
  • Pyridines
  • Recombinant Proteins
  • Niacinamide
  • Sorafenib