A phase II study of sorafenib in combination with bicalutamide in patients with chemotherapy-naive castration resistant prostate cancer

Beardsley, Emma Kate; Hotte, S. J.; North, Scott; Ellard, Susan L.; Winquist, Eric; Kollmannsberger, Christian; Mukherjee, Som D.; N., Kim

doi:10.1007/s10637-011-9722-5

Cited by 42 publications

(25 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…presented encouraging results using a combination therapy of sorafenib with the nonsteroidal anti-androgen bicalutamide in 39 chemotherapy naïve CRPCa patients. PSA declines or stable disease (≥6 months) were observed in 47% of patients including 26% of patients previously progressing on bicalutamide monotherapy [40]. …”

Section: Discussionmentioning

confidence: 99%

Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells

Zengerling

Streicher

Schrader

et al. 2012

IJMS

View full text Add to dashboard Cite

Recent evidence suggests that the development of castration resistant prostate cancer (CRPCa) is commonly associated with an aberrant, ligand-independent activation of the androgen receptor (AR). A putative mechanism allowing prostate cancer (PCa) cells to grow under low levels of androgens, is the expression of constitutively active, C-terminally truncated AR lacking the AR-ligand binding domain (LBD). Due to the absence of a LBD, these receptors, termed ARΔLBD, are unable to respond to any form of anti-hormonal therapies. In this study we demonstrate that the multikinase inhibitor sorafenib inhibits AR as well as ARΔLBD-signalling in CRPCa cells. This inhibition was paralleled by proteasomal degradation of the AR- and ARΔLBD-molecules. In line with these observations, maximal antiproliferative effects of sorafenib were achieved in AR and ARΔLBD-positive PCa cells. The present findings warrant further investigations on sorafenib as an option for the treatment of advanced AR-positive PCa.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells

Zengerling

Streicher

Schrader

et al. 2012

IJMS

View full text Add to dashboard Cite

show abstract

“…Moderate activity was observed, but definitive phase III studies have not been launched and none are planned [9, 10]. Similar results were observed with cediranib (formerly AZD2171), a TKI that is more selective for VEGFR and also blocks activity of c-kit.…”

Section: Targeting Angiogenesismentioning

confidence: 78%

Growth factor and signaling pathways and their relevance to prostate cancer therapeutics

Wozney

Antonarakis

2014

Cancer Metastasis Rev

View full text Add to dashboard Cite

Treatments that target the androgen axis represent an effective strategy for patients with advanced prostate cancer, but the disease remains incurable and new therapeutic approaches are necessary. Significant advances have recently occurred in our understanding of the growth factor and signaling pathways that are active in prostate cancer. In conjunction with this, many new targeted therapies with sound pre-clinical rationale have entered clinical development and are being tested in men with castration-resistant prostate cancer. Some of the most relevant pathways currently being exploited for therapeutic gain are HGF/c-Met signaling, the PI3K/AKT/mTOR pathway, Hedgehog signaling, the endothelin axis, Src kinase signaling, the IGF pathway, and angiogenesis. Here, we summarize the biological basis for the use of selected targeted agents and the results from available clinical trials of these drugs in men with prostate cancer.

show abstract

“…A phase II trial of sorafenib plus bicalutamide in chemotherapy‐naïve CRPC patients with or without metastases reported 47% of patients as having either a PSA response or stable disease at or beyond 6 months. AEs of grade 3 or higher included fatigue, skin rash, and hand‐foot syndrome [68]. Further studies are required to determine the potential of sorafenib in mCRPC and several phase II trials are ongoing [28].…”

Section: New Developments In the Treatment Of Crpcmentioning

confidence: 99%

New developments in castrate‐resistant prostate cancer

Shore¹,

Mason²,

Reijke³

2012

BJU International

View full text Add to dashboard Cite

Castrate‐resistant prostate cancer (CRPC) occurs when disease progresses in the presence of castrate levels of androgens and remains sensitive to further hormonal manipulation. For many years the treatment of CRPC was limited to the use of docetaxel for metastatic disease. However, this has recently changed with the approval of several new agents. Sipuleucel‐T, an immunotherapeutic vaccine, is now available in the US for patients with non‐metastatic CRPC and abiraterone, an oral enzyme inhibitor of androgen biosynthesis, as well as cabazitaxel, a cytotoxic chemotherapeutic, have been approved for the treatment of metastatic CRPC. Also, denosumab, a subcutaneous antibody, is now an option for the treatment of patients with CRPC with bone metastases, in addition to zoledronic acid, an intravenous bisphosphonate. Further treatment advances for metastatic CRPC therapeutics are in late stage phase III development. These include therapies affecting the androgen receptor (MDV3100) as well as additional immune‐based therapeutics, PROSTVAC and ipilimumab. A broad range of agents is also emerging under the term targeted therapies. The endothelin‐A receptor antagonist zibotentan, the tyrosine kinase inhibitors dasatinib, sorafenib and cabozantinib, the anti‐angiogenic agent aflibercept, and the clusterin inhibitor custirsen, are all currently being tested for efficacy in metastatic CRPC. The mechanism of action of these and other promising agents are discussed alongside current therapeutic options and their potential place in the treatment landscape for CRPC is considered.

show abstract

A phase II study of sorafenib in combination with bicalutamide in patients with chemotherapy-naive castration resistant prostate cancer

Abstract: 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.

Cited by 42 publications

References 23 publications

Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells

Effects of Sorafenib on C-Terminally Truncated Androgen Receptor Variants in Human Prostate Cancer Cells

Growth factor and signaling pathways and their relevance to prostate cancer therapeutics

New developments in castrate‐resistant prostate cancer

Contact Info

Product

Resources

About