| Autor: |
Suominen MI; Pharmatest Services Ltd., 20520 Turku, Finland., Knuuttila M; Aurexel Life Sciences Ltd., 21240 Askainen, Finland., Schatz CA; Research & Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Schlicker A; Research & Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Vääräniemi J; Pharmatest Services Ltd., 20520 Turku, Finland., Sjöholm B; Aurexel Life Sciences Ltd., 21240 Askainen, Finland., Alhoniemi E; Inoi Oy, 20100 Turku, Finland., Haendler B; Research & Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Mumberg D; Research & Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany., Käkönen SM; Aurexel Life Sciences Ltd., 21240 Askainen, Finland.; Institute of Biomedicine, University of Turku, 20520 Turku, Finland., Scholz A; Research & Development, Pharmaceuticals, Bayer AG, 13353 Berlin, Germany. |
| Abstrakt: |
Radium-223 dichloride and enzalutamide are indicated for metastatic castration-resistant prostate cancer and their combination is currently being investigated in a large phase 3 clinical trial. Here, we evaluated the antitumor efficacy of radium-223, enzalutamide, and their combination in the intratibial LNCaP model mimicking prostate cancer metastasized to bone. In vitro experiments revealed that the combination of radium-223 and enzalutamide inhibited LNCaP cell proliferation and showed synergistic efficacy. The combination of radium-223 and enzalutamide also demonstrated enhanced in vivo antitumor efficacy, as determined by measuring serum PSA levels in the intratibial LNCaP model. A decreasing trend in the total area of tumor-induced abnormal bone was associated with the combination treatment. The serum levels of the bone formation marker PINP and the bone resorption marker CTX-I were lowest in the combination treatment group and markedly decreased compared with vehicle group. Concurrent administration of enzalutamide did not impair radium-223 uptake in tumor-bearing bone or the ability of radium-223 to inhibit tumor-induced abnormal bone formation. In conclusion, combination treatment with radium-223 and enzalutamide demonstrated enhanced antitumor efficacy without compromising the integrity of healthy bone. The results support the ongoing phase 3 trial of this combination. |
