Optimal Sequencing of New Drugs in Metastatic Castration-Resistant Prostate Cancer: Dream or Reality?

2016 ◽  
Vol 17 (11) ◽  
pp. 1301-1308 ◽  
Author(s):  
Orazio Caffo ◽  
Andrea Lunardi ◽  
Chiara Trentin ◽  
Francesca Maines ◽  
Antonello Veccia ◽  
...  
2013 ◽  
Vol 09 (01) ◽  
pp. 34 ◽  
Author(s):  
Axel Heidenreich ◽  
David Pfister ◽  
Axel Merseburger ◽  
Georg Bartsch ◽  
◽  
...  

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.


2012 ◽  
Vol 08 (02) ◽  
pp. 89
Author(s):  
Guru Sonpavde ◽  
E David Crawford ◽  
◽  

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.


2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e16079-e16079
Author(s):  
Benjamin Louis Maughan ◽  
Daniel L. Suzman ◽  
Rosa Nadal ◽  
Sunakshi Bassi ◽  
Michael Thomas Schweizer ◽  
...  

The Prostate ◽  
2015 ◽  
Vol 75 (15) ◽  
pp. 1814-1820 ◽  
Author(s):  
Benjamin L. Maughan ◽  
Xian C. Xhou ◽  
Daniel L. Suzman ◽  
Rosa Nadal ◽  
Sunakshi Bassi ◽  
...  

2012 ◽  
Vol 08 (01) ◽  
pp. 36 ◽  
Author(s):  
Orazio Caffo ◽  
Giovanni Pappagallo ◽  
Lucianna Maria Russo ◽  
Antonello Veccia ◽  
Enzo Galligioni ◽  
...  

Docetaxel rechallenges are considered to be an option for patients with castration-resistant prostate cancer who responded to first-line docetaxel therapy. The strategy was developed to satisfy the clinical need of fit patients progressing after first-line discontinuation who required an active treatment when no new active drugs were available. A number of reports concerning everyday clinical practice have demonstrated that a rechallenge strategy is safe, feasible and well-tolerated, and improves disease control. The current availability of new second-line drugs that increase patient survival means that the need for rechallenges has been questioned. In this paper, the published data concerning rechallenges are reviewed, concentrating on their use in the light of the availability of new drugs.


2017 ◽  
Vol 9 (8) ◽  
pp. 565-573 ◽  
Author(s):  
Naoki Terada ◽  
Shusuke Akamatsu ◽  
Takashi Kobayashi ◽  
Takahiro Inoue ◽  
Osamu Ogawa ◽  
...  

Advances in our understanding of the mechanisms driving castration-resistant prostate cancer have promoted the development of several new drugs including androgen receptor-directed therapy and chemotherapy. Concomitant docetaxel treatment at the beginning of hormonal therapy for metastatic prostate cancer has resulted in longer overall survival than with hormonal therapy alone. Elucidating an appropriate treatment sequence using these therapies is important for maximizing clinical benefit in castration-sensitive and castration-resistant prostate cancer patients. The development of advanced high-throughput ‘omics’ technology has enabled the use of novel markers to guide prognosis and treatment of this disease. In this review, we outline the genomic landscape of prostate cancer and the molecular mechanisms of castration-resistant progression, and how these affect the development of new drugs, and their clinical implications for selecting treatment sequence. We also discuss many of the potential tissue-based or liquid biomarkers that may soon enter clinical use, with the hope that several of these prognostic or predictive markers will guide precision medicine for prostate cancer patients in the near future.


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