scholarly journals Clinical Development of Cabazitaxel for the Treatment of Castration-Resistant Prostate Cancer

2011 ◽  
Vol 5 ◽  
pp. CMO.S6566 ◽  
Author(s):  
Che-Kai Tsao ◽  
Sonia Seng ◽  
William K. Oh ◽  
Matthew D. Galsky
Keyword(s):  
Prostate Cancer ◽  
Efflux Pump ◽  
Treatment Options ◽  
Clinical Development ◽  
Castration Resistant Prostate Cancer ◽  
Resistant Disease ◽  
Castration Resistant ◽  
P Glycoprotein ◽  
Drug Efflux Pump ◽  
Improvement In Survival

Castration resistant prostate cancer has historically been considered chemotherapy insensitive. However, the approval of estramustine phosphate, mitoxantrone, and docetaxel, over the past few decades, has challenged this notion. Despite these advances, until recently, only docetaxel had been shown to improve survival in patients with castration-resistant disease, and there has been no standard treatment options available for men with disease progression on docetaxel. In the last year, cabazitaxel, a novel taxane with decreased affinity for ATP-dependent drug efflux pump P-glycoprotein, became the first cytotoxic agent to demonstrate an improvement in survival in men with docetaxel-refractory disease, and has received regulatory approval for treatment in this setting. In this review, we examine the clinical development of cabazitaxel for the treatment of castration-resistant prostate cancer, as well as rationale and direction of future therapeutic investigation.

Treatment Given Near the End of Life in Castration-Resistant Prostate Cancer

2012 ◽  
Vol 29 (7) ◽  
pp. 536-540 ◽  
Author(s):  
Hanna A. Zaghloul ◽  
Jose R. Murillo
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
End Of Life ◽  
Treatment Options ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Related Quality ◽  
Impact On Survival ◽  
New Treatments

Chemotherapy treatment options are limited for patients with castration-resistant prostate cancer (CRPC). The purpose of this study is to report treatment use and adverse effects (AEs) within the last three months of life in patients with CRPC. Of the 88 patients identified, 32% received treatment within 3 months of death, and documented AEs occurred in 25% of patients. Of those, neutropenia (18.3%), nausea/vomiting (18.3%), and febrile neutropenia (13.6%) were the most frequent. Results of this study show high treatment utility towards the end-of-life in patients with CRPC, with one fourth of patients experiencing AEs. Attention to health-related quality of life becomes increasingly important as new treatments appear to have small impact on survival, and AEs of those treatments may significantly impact patient quality of life.

Modern Management of Castration-resistant Prostate Cancer

2013 ◽  
Vol 09 (01) ◽  
pp. 34 ◽  
Author(s):  
Axel Heidenreich ◽  
David Pfister ◽  
Axel Merseburger ◽  
Georg Bartsch ◽  
◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Medical Treatment ◽  
Treatment Options ◽  
Treatment Strategies ◽  
New Drugs ◽  
Control Group ◽  
Daily Routine ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223

The approval or clinical evaluation of several new agents – cabazitaxel, enzalutamide, sipuleucel-T, radium-223 and abiraterone acetate – has significantly changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxelbased chemotherapy. All of these agents have resulted in a significant survival benefit compared with their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and the biological aggressiveness of the disease. Furthermore, treatment-associated side effects differ between the various drugs. As new drugs are approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. It is the aim of this article to (1) summarise the data of established treatment options in mCRPC, (2) highlight new developments of medical treatment, (3) provide clinically useful algorithms for the daily routine and to (4) point out future developments of medical treatment.

CASTRATION-RESISTANT PROSTATE CANCER: NEW PERSPECTIVES IN PHARMACOLOGICAL TREATMENT

2019 ◽  
Vol 25 (1) ◽  
pp. 49-58
Author(s):  
Dmitry A. Andreev ◽  
A. A Zavyalov ◽  
A. V Govorov ◽  
K. A. Kokushkin ◽  
M. Y Davidovskaya
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Treatment Options ◽  
Specific Treatment ◽  
Cochrane Library ◽  
Cancer Drug ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Treatment Algorithms ◽  
Castration Resistant

Prostate cancer remains one of the most actual problems in oncourology due to its high prevalence and resistance to therapy. Within 5 years of active treatment and follow-up, the castration-resistant prostate cancer (CRPC) develops in 10-20% of patients. This type of disease course resists treatments and leads to death. Medical resources distinguish two different forms of CRPC: non-metastatic and metastatic. Such separation is critically important because each of two forms requires different treatment algorithms. This paper summarizes the main outlines of foreign clinical guidelines and reviews the new treatment options for non-metastatic and metastatic CRPC as wells as the design and results of key clinical trials on drug efficiency. To prepare the review, the comprehensive literature search was conducted using PubMed/Medline, the Cochrane Library, EMBASE, CyberLeninka, e-library databases. The search line included phrases containing the following words: prostate cancer, castration-resistant prostate cancer, drug therapy, treatment algorithms, clinical studies, etc. In accordance to foreign guidelines, it is essential to determine the high risk patients with non-metastatic CRPC and promptly apply new therapeutic options including apalutamide and enzalutamide, which have proven being effective in clinical trials as therapies that attenuate the transition of the non-metastatic CRPC to the metastatic stage. Foreign medical guidelines propose to apply a wider set of treatment algorithms for patients with metastatic CRPC, for instance: considerations on possibilities to use the cabazitaxel instead of docetaxel in the 1st line therapy in patients with pre-existing mild peripheral neuropathy, etc. as well as new therapies - pembrolizumab and sipuleucel-T. The issues regarding the selection of patients with CRPC for specific treatment algorithms and defining the optimal sequence of therapeutic regimens as well as combining various regimens with minimizing toxic effects and maximizing patient benefits remain unsolved.

Castration-resistant Prostate Cancer – Chemotherapies and Molecular Targets

2013 ◽  
Vol 09 (01) ◽  
pp. 27
Author(s):  
Amit Bahl ◽  
Keyword(s):  
Prostate Cancer ◽  
Survival Rates ◽  
Signal Transduction Pathway ◽  
Molecular Targets ◽  
Abiraterone Acetate ◽  
Clinical Development ◽  
Transduction Pathway ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Castration-resistant prostate cancer has a poor prognosis: current chemotherapeutic approaches ultimately result in resistance and are associated with survival rates of less than 2 years. However, the last decade has seen an expansion in the number of therapeutic options for CRPC and the regulatory approval of several agents, including the chemotherapy drug cabazitaxel and the targeted agents abiraterone acetate, enzalatumide and denosumab. Novel targeted agents inhibit androgen receptor-mediated signalling, and non-hormonal targets, including apoptosis, signal transduction pathway inhibitors, angiogenesis and bone and immune microenvironments. Clinical trials of these agents, however, have demonstrated varied efficacy. Among the drugs in clinical development, custirsen, cabozantinib and dasatinib are among the most promising. There is a requirement for studies directly comparing agents, and for improved patient selection to identify patients benefitting from a particular therapy.

Castration-resistant Prostate Cancer— Chemotherapies and Molecular Targets

2013 ◽  
Vol 09 (02) ◽  
pp. 90
Author(s):  
Amit Bahl ◽  
Keyword(s):  
Prostate Cancer ◽  
Survival Rates ◽  
Signal Transduction Pathway ◽  
Molecular Targets ◽  
Abiraterone Acetate ◽  
Clinical Development ◽  
Transduction Pathway ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Castration-resistant prostate cancer (CRPC) has a poor prognosis: current chemotherapeutic approaches ultimately result in resistance and are associated with survival rates of less than 2 years. However, the last decade has seen an expansion in the number of therapeutic options for CRPC and the regulatory approval of several agents, including the chemotherapy drug cabazitaxel and the targeted agents abiraterone acetate, enzalatumide, and denosumab. Novel targeted agents inhibit androgen receptor-mediated signaling, and nonhormonal targets, including apoptosis, signal transduction pathway inhibitors, angiogenesis, and bone and immune microenvironments. Clinical trials of these agents, however, have demonstrated varied efficacy. Among the drugs in clinical development, custirsen, cabozantinib, and dasatinib are among the most promising. There is a requirement for studies directly comparing agents, and for improved patient selection to identify patients benefitting from a particular therapy.

scholarly journals Assessment of Skeletal Tumor Load in Metastasized Castration-Resistant Prostate Cancer Patients: A Review of Available Methods and an Overview on Future Perspectives

2018 ◽  
Vol 5 (3) ◽  
pp. 58 ◽  
Author(s):  
Francesco Fiz ◽  
Helmut Dittman ◽  
Cristina Campi ◽  
Silvia Morbelli ◽  
Cecilia Marini ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Treatment Options ◽  
Automated Analysis ◽  
Tumor Burden ◽  
Reference List ◽  
Castration Resistant Prostate Cancer ◽  
Skeletal Tissue ◽  
Progressive Development ◽  
Castration Resistant ◽  
Number Of Treatment

Metastasized castration-resistant prostate cancer (mCRPC), is the most advanced form of prostate neoplasia, where massive spread to the skeletal tissue is frequent. Patients with this condition are benefiting from an increasing number of treatment options. However, assessing tumor response in patients with multiple localizations might be challenging. For this reason, many computational approaches have been developed in the last decades to quantify the skeletal tumor burden and treatment response. In this review, we analyzed the progressive development and diffusion of such approaches. A computerized literature search of the PubMed/Medline was conducted, including articles between January 2008 and March 2018. The search was expanded by manually reviewing the reference list of the chosen articles. Thirty-five studies were identified. The number of eligible studies greatly increased over time. Studies could be categorized in the following categories: automated analysis of 2D scans, SUV-based thresholding, hybrid CT- and SUV-based thresholding, and MRI-based thresholding. All methods are discussed in detail. Automated analysis of bone tumor burden in mCRPC is a growing field of research; when choosing the appropriate method of analysis, it is important to consider the possible advantages as well as the limitations thoroughly.

scholarly journals Enzalutamide therapy for advanced prostate cancer: efficacy, resistance and beyond

2019 ◽  
Vol 26 (1) ◽  
pp. R31-R52 ◽  
Author(s):  
Simon Linder ◽  
Henk G van der Poel ◽  
Andries M Bergman ◽  
Wilbert Zwart ◽  
Stefan Prekovic
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Advanced Prostate Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Treatment Resistance ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Castration Resistant ◽  
Novel Drugs

The androgen receptor drives the growth of metastatic castration-resistant prostate cancer. This has led to the development of multiple novel drugs targeting this hormone-regulated transcription factor, such as enzalutamide – a potent androgen receptor antagonist. Despite the plethora of possible treatment options, the absolute survival benefit of each treatment separately is limited to a few months. Therefore, current research efforts are directed to determine the optimal sequence of therapies, discover novel drugs effective in metastatic castration-resistant prostate cancer and define patient subpopulations that ultimately benefit from these treatments. Molecular studies provide evidence on which pathways mediate treatment resistance and may lead to improved treatment for metastatic castration-resistant prostate cancer. This review provides, firstly a concise overview of the clinical development, use and effectiveness of enzalutamide in the treatment of advanced prostate cancer, secondly it describes translational research addressing enzalutamide response vs resistance and lastly highlights novel potential treatment strategies in the enzalutamide-resistant setting.

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