Castrate-resistant Prostate Cancer—Recent Advances in Therapy and Future Perspectives

2013 ◽  
Vol 09 (01) ◽  
pp. 16
Author(s):  
Alan J Koletsky ◽  
Keyword(s):  
Prostate Cancer ◽  
Skeletal Metastases ◽  
Bone Microenvironment ◽  
Resistant Disease ◽  
Recent Advances ◽  
Castrate Resistant Prostate Cancer ◽  
Skeletal Related Events ◽  
Castrate Resistant ◽  
The Many

For many years, few therapeutic options were available for the treatment of advanced prostate cancer. Recent advances in our understanding of the molecular biology of prostate cancer, particularly in the transition to castrate resistant disease, have led to the development of more potent and selective endocrine therapies. In addition, elucidation of the many factors in the bone microenvironment that promote the development and subsequent progression of skeletal metastases has led to the discovery of new bone-targeting agents that can delay the onset of skeletal related events and improve quality of life and survival. This review will highlight recently approved novel agents as well as others currently under investigation for the treatment of castrate-resistant prostate cancer (CRPC).

scholarly journals Targeting Bone Metastases in Metastatic Castration-Resistant Prostate Cancer

2016 ◽  
Vol 10s1 ◽  
pp. CMO.Ss30751 ◽  
Author(s):  
Joelle El-Amm ◽  
Jeanny B. Aragon-Ching
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Castration Resistant Prostate Cancer ◽  
Bone Microenvironment ◽  
Skeletal Involvement ◽  
Radium 223 ◽  
The Us ◽  
Castrate Resistant Prostate Cancer ◽  
Skeletal Related Events ◽  
Castrate Resistant

Skeletal involvement in metastatic castrate-resistant prostate cancer (mCRPC) is common and results in significant morbidity and mortality. The interaction of prostate cancer with the bone microenvironment contributes to progression of cancer in the bone leading to skeletal-related events (SREs). Studies aimed at targeting the bone have been carried out over the recent years. Bisphosphonates are synthetic pyrophosphate analogs first investigated for their role in SRE prevention with zoledronic acid as the main bisphosphonate that is approved by the US Food and Drug Administration for retardation of skeletal events in men with metastatic prostate cancer. Denosumab is another bone-targeted agent against uncontrolled osteolysis and serves as a RANK ligand inhibitor, superior to zoledronic acid in delaying SREs. Radiopharmaceuticals have played a role in targeting the bone microenvironment mainly in pain palliation in mCRPC utilizing strontium or samarium in the remote past, but only radium-223 is the first radiopharmaceutical that has yielded improvement in overall survival. The combination and sequencing strategies of these agents is the subject of multiple ongoing trials to guide the best use of these emerging agents.

scholarly journals 225Actinium-labeled prostate-specific membrane antigen targeting peptide induces complete response in a metastatic prostate cancer patient

2021 ◽  
Vol 10 (5) ◽  
pp. 205846012110225
Author(s):  
Omer Aras ◽  
Stefan Harmsen ◽  
Richard Ting ◽  
Haluk B Sayman
Keyword(s):  
Prostate Cancer ◽  
Standard Of Care ◽  
Complete Response ◽  
Prostate Specific Membrane Antigen ◽  
Limited Data ◽  
Castrate Resistant Prostate Cancer ◽  
Targeting Peptide ◽  
Castrate Resistant ◽  
Specific Membrane

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to 225Ac-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive 177Lu-PSMA-617. In addition, the patient’s baseline germline mutation likely predisposed him to more aggressive disease.

Association of health-related quality of life (HRQOL) variations with biological biomarkers for patients with metastatic castrate-resistant prostate cancer (MCRPC) treated by abiraterone/prednisone combination or prednisone.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 54-54
Author(s):  
Morgan Goujon ◽  
Amelie Anota ◽  
Alexandre Frontczak ◽  
Emilie Charton ◽  
Tristan Maurina ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Phase Iii ◽  
Health Related Quality ◽  
Meaningful Improvement ◽  
Related Quality ◽  
Health Related ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

54 Background: A potential link between Health-Related Quality of life (HRQoL) and oncologic outcomes such as overall survival or progression-free survival has been underlined for endocrine therapies in patients with metastatic castrate resistant prostate cancer (mCRPC). Other surrogates such as circulating tumor cells (CTCs) or PSA can be used to evaluate disease control. This study explored the associations between HRQoL and biological biomarkers for patients with mCRPC treated by abiraterone / prednisone or prednisone within registration phase III trial COU-AA-301. Methods: Baseline differences of HRQoL evaluated with FACT-P total score (FACT-P TS) according to biological parameters (including CTCs and PSA) and links between HRQoL's change and variations of these parameters were assessed. The primary objective was to estimate the association between improvement or deterioration in FACT-P TS and the variations of CTCs and PSA. All analyses were conducted using clinically meaningful improvement and deterioration in FACT-P TS and subscales. Results: Among 1130 patients enrolled, 1111 (98.3%) had a baseline FACT-P TS available. At baseline, a favorable CTCs count was associated with higher FACT-P TS compared to unfavorable CTCs (difference in means 8 points, [95% CI, 4 to 12] p < 0.001). At 3 months, there were differences in mean change from baseline FACT-P TS favoring patients with biomarkers response, with clinically meaningful difference for CTCs (12.7 points, [95% CI, 6 to 19.5%] p < 0.001) and PSA (11.64 points, [95% CI, 9.3 to 14] p < 0.0001). Biological progression was associated with higher risk of FACT-P TS worsening for PSA (Odds Ratio (OR) 2.8 [95% CI, 1.9 to 4.2]) with more frequent FACT-P TS improvement in case of response for CTCs (OR 3.14 [95% CI, 1.3 to 7.7]) and PSA (OR 2.9 [95% CI 2.1 to 4]). Significantly longer time until definitive deterioration was observed for patients with CTCs or PSA response (p < 0.001) and shorter time in case of progression (p < 0.001). Conclusions: QUA-lify is the first study to show an association between HRQoL and biomarkers outcomes in patients with mCRPC treated with endocrine therapy in a post-taxane setting. This concept is reinforced by the consistency of the association for all analyses carried out.

Novel methodology for cost evaluation of anticancer drugs in castrate-resistant prostate cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 200-200 ◽  
Author(s):  
Helmy M. Guirgis
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Anticancer Drugs ◽  
Reference Value ◽  
Cost Evaluation ◽  
Life Threatening ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Fatal Adverse Events

200 Background: There is a need for a screening methodology to evaluate cost effectiveness of anticancer drugs. High costs raise concerns on approval, affordability and utilization. Objectives: Develop simplified methodology to screen and score cost versus value survival of docetaxel, cabazitaxel, abiraterone and sipuleucel-T in castrate- resistant prostate cancer (CRPC) Methods: Estimated costs in US $ of the entire course of an evaluated drug were added to downstream ancillary costs. The total was divided by the reported median survival gain over control in days. A reference value scale between 0- 100% was constructed with 0% assigned to cost/overall survival (OS) > $750, life threatening/ fatal adverse events (AEs) and worsened quality of life (QoL). A plan was designed to correct for AEs and QoL. Results were expressed as cost/OS and value and corrected scores. Results: Abiraterone at $5,000 per month x 6 months demonstrated cost/OS of $256 with 66% value and 61% corrected scores. Abiraterone x 9-12 months raised cost/OS and decreased scores. Generic docetaxel x 8 cycles demonstrated $63 cost/OS and 92% value score. Ancillary treatment increased cost/OS to $136 and decreased score to 82%. Cost/OS of cabazitaxel x 6 cycles ranged from $477- $596 with 21-36% scores. Corrections for AEs and QoL reduced scores to 6-21%. Sipuleucel-T demonstrated relatively higher cost/OS and lower scores. Conclusions: Preliminary findings would support utilization of docetaxel and abiraterone more than cabazitaxel and sipuleucel-T. The proposed methodology of cost versus value-survival could facilitate cost evaluation and budgetary planning of anticancer drugs.

scholarly journals Disparity in public funding of therapies for metastatic castrate-resistant prostate cancer across Canadian provinces

2018 ◽  
Vol 12 (10) ◽  
Author(s):  
Dixon T.S. Woon ◽  
Thenappan Chandrasekar ◽  
Lorne Aaron ◽  
Naveen S. Basappa ◽  
Kim N. Chi ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Prince Edward Island ◽  
Public Funding ◽  
Abiraterone Acetate ◽  
Radium 223 ◽  
Castrate Resistant Prostate Cancer ◽  
Canadian Provinces ◽  
Castrate Resistant

Introduction: Treatment using abiraterone acetate plus prednisone, enzalutamide, cabazitaxel, and radium-223 (Ra-223) improves overall survival (OS) and quality of life for patients with metastatic castrate-resistant prostate cancer (mCRPC). Despite their proven benefits, access to these therapies is not equal across Canada.Methods: We describe provincial differences in access to approved mCRPC therapies. Data sources include the pan-Canadian Oncology Drug Review database, provincial cancer care resources, and correspondence with pharmaceutical companies.Results: Both androgen receptor-axis-targeted therapies (ARATs), abiraterone acetate plus prednisone and enzalutamide, are funded by provinces in the pre-and post-chemotherapy setting, however, sequential ARAT use is not funded. “Sandwich” therapy, where one ARAT is used pre-chemotherapy and a second is used upon progression on chemotherapy, is funded in six provinces: Ontario (ON), Alberta, New Brunswick, Prince Edward Island (PEI), Nova Scotia (NS), and Newfoundland and Labrador. Ra-223 is funded in five provinces: ON, Quebec (QC), British Columbia (BC), Saskatchewan, and Manitoba to varying degrees; ON allows Ra-223 either pre- or post-chemo (not both); QC allows Ra-223 post-chemo unless chemo is not tolerated; BC allows Ra-223 if other life-prolonging mCRPC therapies have been received or ineligible. Cabazitaxel is funded in all provinces post-docetaxel, except QC and PEI. Cabazitaxel is not funded as fist-line treatment for mCPRC or in combination with other agents. In ON, BC, QC, and PEI, cabazitaxel is not funded after progression on an ARAT in the post-chemotherapy setting.Conclusions: While all provinces have access to docetaxel and ARATs, sandwiching sequential ARATs with docetaxel is funded only in select provinces. Ra-223 and cabazitaxel access is not ubiquitous across Canada. Such inequalities in access to life-prolonging therapies could lead to disparities in survival and quality of life among patients with mCRPC. Further research should quantify interprovincial variation in outcomes and cost that may result from variable access.

scholarly journals EXTREQOL Identifies Ongoing Challenges in Maximising Quality of Survival in Men with Metastatic Castrate-resistant Prostate Cancer

2018 ◽  
Vol 30 (6) ◽  
pp. 331-333 ◽  
Author(s):  
V. Jenkins ◽  
H. Payne ◽  
M. Mason ◽  
S. May ◽  
L. Matthews ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant
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