A Phase II Study of Sorafenib in Combination with Bicalutamide in Patients with Chemotherapy-naive Castration Resistant Prostate Cancer

Overview

Journal Invest New Drugs

Publisher Springer

Specialty Oncology

Date 2011 Jul 26

PMID 21785998

Citations 18

Authors

Emma K Beardsley

Sebastien J Hotte

Scott North

Susan L Ellard

Eric Winquist

Christian Kollmannsberger

Som D Mukherjee

Kim N Chi

Affiliations

Soon will be listed here.

Abstract

Purpose: The objective of this trial was to evaluate the clinical effects of sorafenib, a multi-targeted kinase inhibitor, in combination with androgen receptor blockade in patients with castration-resistant prostate cancer.

Methods: This was a multicenter, two-stage, phase 2 trial. Eligible patients had rising PSA, minimal symptoms and were chemotherapy-naïve. Sorafenib 400 mg twice daily was administered with bicalutamide 50 mg once daily on a 28-day cycle. The primary endpoint was PSA response (≥ 50% decline) or stable disease ≥ 6 months.

Results: 39 patients were enrolled including eight without clinical evidence of metastases. Eighteen (47%) patients have had either a PSA response or stable disease ≥ 6 months. PSA declines of ≥ 50% occurred in 12 (32%) of 38 assessable patients, including seven of 27 patients (26%) with prior anti-androgen use. Median time to treatment failure was 5.5 months (95%CI = 4.8.1-8.3). Grade ≥ 3 adverse events included fatigue, skin rash, and hand-foot syndrome.

Conclusions: PSA declines and stable disease were observed with a combination of sorafenib and bicalutamide including in patients previously progressing on bicalutamide. Strategies to combine multi-targeted kinase inhibitors with hormonal therapies warrant further study in patients with CRPC.

Citing Articles

New Therapeutic Perspectives in Prostate Cancer: Patient-Derived Organoids and Patient-Derived Xenograft Models in Precision Medicine.

Rago V, Perri A, Di Agostino S Biomedicines. 2023; 11(10).

PMID: 37893116 PMC: 10604340. DOI: 10.3390/biomedicines11102743.

Unique Spectrum of Activating BRAF Alterations in Prostate Cancer.

Chehrazi-Raffle A, Tukachinsky H, Toye E, Sivakumar S, Schrock A, Bergom H Clin Cancer Res. 2023; 29(19):3948-3957.

PMID: 37477913 PMC: 10543965. DOI: 10.1158/1078-0432.CCR-23-1393.

Co-administration of tyrosine kinase inhibitors with rottlerin in metastatic prostate cancer cells.

Cieslikowski W, Haber T, Krajnak S, Anic K, Hasenburg A, Mager R EXCLI J. 2021; 20:1585-1596.

PMID: 34924906 PMC: 8678056. DOI: 10.17179/excli2021-3980.

Combined Anti-Cancer Effects of Platycodin D and Sorafenib on Androgen-Independent and PTEN-Deficient Prostate Cancer.

Lu Z, Song W, Zhang Y, Wu C, Zhu M, Wang H Front Oncol. 2021; 11:648985.

PMID: 34026624 PMC: 8138035. DOI: 10.3389/fonc.2021.648985.

Patient-derived xenografts and organoids model therapy response in prostate cancer.

Karkampouna S, La Manna F, Benjak A, Kiener M, De Menna M, Zoni E Nat Commun. 2021; 12(1):1117.

PMID: 33602919 PMC: 7892572. DOI: 10.1038/s41467-021-21300-6.

References

Sweeney P, Karashima T, Kim S, Kedar D, Mian B, Huang S . Anti-vascular endothelial growth factor receptor 2 antibody reduces tumorigenicity and metastasis in orthotopic prostate cancer xenografts via induction of endothelial cell apoptosis and reduction of endothelial cell matrix metalloproteinase type 9.... Clin Cancer Res. 2002; 8(8):2714-24. View

Bakin R, Gioeli D, Bissonette E, Weber M . Attenuation of Ras signaling restores androgen sensitivity to hormone-refractory C4-2 prostate cancer cells. Cancer Res. 2003; 63(8):1975-80. View

Scher H, Beer T, Higano C, Anand A, Taplin M, Efstathiou E . Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010; 375(9724):1437-46. PMC: 2948179. DOI: 10.1016/S0140-6736(10)60172-9. View

Taylor B, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver B . Integrative genomic profiling of human prostate cancer. Cancer Cell. 2010; 18(1):11-22. PMC: 3198787. DOI: 10.1016/j.ccr.2010.05.026. View

Palanisamy N, Ateeq B, Kalyana-Sundaram S, Pflueger D, Ramnarayanan K, Shankar S . Rearrangements of the RAF kinase pathway in prostate cancer, gastric cancer and melanoma. Nat Med. 2010; 16(7):793-8. PMC: 2903732. DOI: 10.1038/nm.2166. View

de Bono J, Logothetis C, Molina A, Fizazi K, North S, Chu L . Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011; 364(21):1995-2005. PMC: 3471149. DOI: 10.1056/NEJMoa1014618. View

George D, Halabi S, Shepard T, Vogelzang N, Hayes D, Small E . Prognostic significance of plasma vascular endothelial growth factor levels in patients with hormone-refractory prostate cancer treated on Cancer and Leukemia Group B 9480. Clin Cancer Res. 2001; 7(7):1932-6. View

Bubley G, Carducci M, Dahut W, Dawson N, Daliani D, Eisenberger M . Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol. 1999; 17(11):3461-7. DOI: 10.1200/JCO.1999.17.11.3461. View

Tannock I, de Wit R, Berry W, Horti J, Pluzanska A, Chi K . Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004; 351(15):1502-12. DOI: 10.1056/NEJMoa040720. View

10.

Huss W, Hanrahan C, Barrios R, Simons J, Greenberg N . Angiogenesis and prostate cancer: identification of a molecular progression switch. Cancer Res. 2001; 61(6):2736-43. View

11.

Therasse P, Arbuck S, Eisenhauer E, Wanders J, Kaplan R, Rubinstein L . New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92(3):205-16. DOI: 10.1093/jnci/92.3.205. View

12.

Escudier B, Eisen T, Stadler W, Szczylik C, Oudard S, Siebels M . Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med. 2007; 356(2):125-34. DOI: 10.1056/NEJMoa060655. View

13.

Suzuki H, Okihara K, Miyake H, Fujisawa M, Miyoshi S, Matsumoto T . Alternative nonsteroidal antiandrogen therapy for advanced prostate cancer that relapsed after initial maximum androgen blockade. J Urol. 2008; 180(3):921-7. DOI: 10.1016/j.juro.2008.05.045. View

14.

Feldman B, Feldman D . The development of androgen-independent prostate cancer. Nat Rev Cancer. 2002; 1(1):34-45. DOI: 10.1038/35094009. View

15.

Small E, Halabi S, Dawson N, Stadler W, Rini B, Picus J . Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004; 22(6):1025-33. DOI: 10.1200/JCO.2004.06.037. View

16.

Joyce R, Fenton M, Rode P, Constantine M, Gaynes L, Kolvenbag G . High dose bicalutamide for androgen independent prostate cancer: effect of prior hormonal therapy. J Urol. 1997; 159(1):149-53. DOI: 10.1016/s0022-5347(01)64039-4. View

17.

Saad F, Gleason D, Murray R, Tchekmedyian S, Venner P, Lacombe L . A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst. 2002; 94(19):1458-68. DOI: 10.1093/jnci/94.19.1458. View

18.

Llovet J, Ricci S, Mazzaferro V, Hilgard P, Gane E, Blanc J . Sorafenib in advanced hepatocellular carcinoma. N Engl J Med. 2008; 359(4):378-90. DOI: 10.1056/NEJMoa0708857. View

19.

Olsson A, Bjork A, Vallon-Christersson J, Isaacs J, Leanderson T . Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors. Mol Cancer. 2010; 9:107. PMC: 2885345. DOI: 10.1186/1476-4598-9-107. View

20.

Simon R . Optimal two-stage designs for phase II clinical trials. Control Clin Trials. 1989; 10(1):1-10. DOI: 10.1016/0197-2456(89)90015-9. View