scholarly journals Bone Targeting Agents in Patients with Metastatic Prostate Cancer: State of the Art

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 546
Author(s):  
Veronica Mollica ◽  
Alessandro Rizzo ◽  
Matteo Rosellini ◽  
Andrea Marchetti ◽  
Angela Dalia Ricci ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cord Compression ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Pathologic Fractures ◽  
Phase Iii Trials ◽  
Skeletal Related Events

Bone health represents a major issue in castration-resistant prostate cancer (CRPC) patients with bone metastases; in fact, the frequently prolonged use of hormonal agents causes important modifications in physiological bone turnover and most of these men will develop skeletal-related events (SREs), including spinal cord compression, pathologic fractures and need for surgery or radiation to bone, which are estimated to occur in almost half of this patient population. In the last decade, several novel therapeutic options have entered into clinical practice of bone metastatic CRPC, with recent approval of enzalutamide and abiraterone acetate, cabazitaxel chemotherapy and radium-223, on the basis of survival benefit suggested by landmark Phase III trials assessing these agents in this setting. Conversely, although bone-targeted agents (BTAs)—such as the bisphosphonate zoledronic acid and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab—are approved for the prevention of SREs, these compounds have not shown benefit in terms of overall survival. However, emerging evidence has suggested that the combination of BTAs and abiraterone acetate, enzalutamide and the radiopharmaceutical radium-223 could result in improved clinical outcomes and prolonged survival in bone metastatic CRPC. In this review, we will provide an overview on bone tropism of prostate cancer and on the role of BTAs in metastatic hormone-sensitive and castration-resistant prostate cancer.

Novel therapies and emerging strategies for the treatment of patients with castration-resistant prostate cancer

2017 ◽  
Author(s):  
Deborah Mukherji ◽  
Aurelius Omlin ◽  
Carmel Pezaro ◽  
Johann De Bono
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Phase Iii ◽  
Trial Participation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
New Treatments ◽  
Phase Iii Studies ◽  
Clinical And Translational Research

Castration-resistant prostate cancer (CRPC) represents a final stage of this malignancy for many men and is defined as the progression of prostate cancer despite castrate levels of testosterone. CRPC may present as a rising PSA, the development of new metastases, or worsening of known metastases. Recent advances have resulted in five new treatments for CRPC: the immunotherapy sipuleucel-T; the cytotoxic cabazitaxel; the androgen biosynthesis inhibitor abiraterone acetate; the radioisotope radium-223; and the antiandrogen enzalutamide. These have all improved overall survival in randomized phase III studies for patients with metastatic CRPC. Furthermore, multiple agents and combinations are currently in late-stage clinical testing. Men with advanced prostate cancer represent an important population for clinical and translational research and clinical trial participation should be considered as part of standard care.

State-of-the-Art Management for the Patient with Castration-Resistant Prostate Cancer in 2012

2012 ◽  
pp. 289-291 ◽  
Author(s):  
Oliver Sartor
Keyword(s):  
Prostate Cancer ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Molecular Stratification ◽  
Castration Resistant ◽  
Radium 223 ◽  
Phase Iii Trials

Overview: Much progress has been made in metastatic castration-resistant prostate cancer (CRPC), and multiple new U.S. Food and Drug Administration (FDA)-approved survival-prolonging drugs are now available. In 2004, docetaxel/prednisone was the first therapy shown to prolong survival. In 2010 and 2011, sipuleucel-T, cabazitaxel/prednisone, and abiraterone/prednisone were FDA approved. Two new agents, radium-223 and MDV-3100, have recently reported large phase III trials prolonging overall survival and will be submitted for regulatory approval in 2012. One can now begin to ask, is there an optimal sequence for therapies in metastatic CRPC? Despite the recent progress, there is much we do not know and virtually no information on this important question. We know that abiraterone/prednisone and cabazitaxel/prednisone are appropriate choices for a patient after receiving docetaxel, but we do not know what, if anything, represents the optimal sequence for abiraterone and cabazitaxel. In fact we do not understand how one therapy may affect the response to a subsequent therapy. We are also aware that the pre- and postdocetaxel spaces represent regulatory rather than biologic divisions. In addition, despite the proven role of docetaxel/prednisone, many patients with CRPC are not considered to be suitable for chemotherapy, and worldwide many never receive any form of chemotherapy. What is the optimal management for these patients? Taken together it is reasonable to assess patient preferences, prior therapies and response/tolerance to prior therapies, burden of disease, comorbidities, current symptoms, drug toxicities, out-of-pocket costs, etc., in clinical decision making. Given the many factors we do not know, it is hard to be dogmatic in approaching the therapeutic options for the patient with CRPC. We will likely soon move beyond the current sequencing paradigm and begin to assess new combinations in a systematic and rational fashion. Perhaps one day, in the not too distant future, we will develop molecular “stratification systems” to better guide therapeutic choices in CRPC.

Recent Developments in Treatments for Metastatic Castration-resistant Prostate Cancer—A Mechanistic Perspective

2012 ◽  
Vol 08 (02) ◽  
pp. 89
Author(s):  
Guru Sonpavde ◽  
E David Crawford ◽  
◽  
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Chemotherapeutic Agents ◽  
New Drugs ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Microtubule Inhibitor ◽  
Phase Iii Clinical Trials ◽  
Castration Resistant ◽  
Radium 223

Over the past decade, the treatment landscape in metastatic castration-resistant prostate cancer (CRPC) has markedly changed, with the introduction of three new chemotherapeutic agents. The mechanism of CRPC is not fully understood, but it may result from multiple pathways, including a loss or androgen receptor (AR) specificity and increased downstream signalling activity that provide multiple targets for therapeutic agents. For some years, docetaxel was the mainstay of treatment in CRPC, but recently, cabazitaxel (a microtubule inhibitor), sipuleucel-T (a cancer vaccine), and abiraterone acetate (a CYP17 inhibitor) were approved for CRPC treatment. In Phase III clinical trials, these agents have shown significant improvements in survival—over mitoxantrone (for cabazitaxel) and over placebo (for sipuleucel-T and abiraterone acetate)—and were well tolerated. There are also two treatments in late-stage development, MDV3100 (an oral AR antagonist) and radium-223 (an isotope that creates breaks in double-stranded DNA). These have also shown improvements in survival in Phase III trials; their regulatory approval is expected soon. The modes of actions of the existing and new drugs in CRPC are varied, but some are complementary and investigations of different combinations of these medications are much needed; they may enhance efficacy, further extend survival, and improve outcomes in this formerly untreatable disease.

Nonhormone Therapy for Metastatic Castration-Resistant Prostate Cancer: Chemotherapy, Bone-Targeted Treatments, and Others

2013 ◽  
pp. e161-e165
Author(s):  
Karim Fizazi
Keyword(s):  
Prostate Cancer ◽  
Kinase Inhibitors ◽  
Time Frame ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
New Agents ◽  
Castration Resistant ◽  
Radium 223 ◽  
Targeted Treatments ◽  
Phase Iii Trials

There is no doubt that more therapeutic progress has been achieved during the last 3 years for patients with metastatic castration-resistant prostate cancer (mCRPC) than during the previous 30 years. During this limited time frame, not only have six compounds (sipuleucel-T, cabazitaxel, denosumab, abiraterone, radium-223, and enzalutamide, listed in chronologic order) yielded positive results in phase III trials, we have also learned that their mechanisms of action are different, making it quite likely that part of their anticancer activity may be incremental. Most of these agents have already been approved. Further progress may well soon complete this recently enlarged armamentarium, with important trials testing new agents derived from existing families of compounds (new endocrine therapies, new immunotherapies, etc.) and exploring the activity of new families of agents (tyrosine kinase inhibitors such as cabozantinib, inhibitors of chaperone proteins like OGX-O11 and OGX-427). The availability of these agents creates a new major challenge for those who conduct clinical research in mCRPC. Will we be able to personalize therapy based on the biology of the individual's tumor, as we are already doing in other neoplasms?

Clinical outcome with concurrent or layered treatment with radium-223 and abiraterone: A retrospective study of real-world experience with patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 253-253 ◽  
Author(s):  
Daniel J. George ◽  
Cora N. Sternberg ◽  
A. Oliver Sartor ◽  
Fred Saad ◽  
Bertrand F. TOMBAL ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Retrospective Study ◽  
Clinical Outcomes ◽  
Real World ◽  
Descriptive Analysis ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Radium 223 ◽  
Pathologic Fractures ◽  
Skeletal Related Events

253 Background: Limited data exist on Ra-223 use in combination with Abi in a real-world setting. This retrospective study evaluated clinical outcomes in pts with mCRPC who received concurrent or layered Ra-223 + Abi treatment. Methods: This study used the Flatiron prostate cancer registry of electronic health records of pts with mCRPC treated with Ra-223 in US cancer clinics between 1/01/2013 and 6/30/2017. Two sub-cohorts were defined: pts treated with Ra-223 + Abi in a concurrent (both started within 30 days) or layered fashion (one of the two started over 30 days later). Descriptive analysis was done for baseline (BL) characteristics (prior to start of Ra-223), prior therapies, and clinical outcomes including skeletal-related events (SREs) and overall survival (OS). Results: 625 pts were treated with Ra-223; 136 (21.8%) received Ra-223 + Abi. Most received layered therapy (n = 97, 71%); concurrent start was less common (n = 39, 29%) [Table]. Conclusions: Prior to the start of Ra-223 therapy, half of the pts had prior SREs; almost one-fifth had prior pathologic fractures. Pts treated with Ra-223 + Abi had also received prior chemo and/or enzalutamide. SRE occurrence seems higher for concurrent treatment, but results should be cautiously interpreted due to low concurrent cohort size. OS in both cohorts exceeded the OS in the Phase III ALSYMPCA study (14.9 mo).[Table: see text]

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