Combination therapy of interleukin-2 and sorafenib improves survival benefits and prevents spontaneous pulmonary metastasis in murine renal cell carcinoma models.
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.
Amagai
Yosuke
Y
Discovery Research Laboratories, Shionogi & Co., Ltd, Osaka, Japan.
Matsumoto
Mitsunobu
M
Hojo
Kanji
K
Iguchi
Motofumi
M
Wada
Tooru
T
Tanaka
Hidekazu
H
Ide
Nobuyuki
N
Kato
Akira
A
Shichijo
Michitaka
M
Abe
Kenji
K
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
D001557:Benzenesulfonates; D007376:Interleukin-2; D010671:Phenylurea Compounds; D011725:Pyridines; D011994:Recombinant Proteins; D009536:Niacinamide; D000077157:Sorafenib