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Metastatic prostatic cancer clinical treatment

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https://www.readbyqxmd.com/read/29049492/association-of-hsd3b1-genotype-with-response-to-androgen-deprivation-therapy-for-biochemical-recurrence-after-radiotherapy-for-localized-prostate-cancer
#1
Jason W D Hearn, Wanling Xie, Mari Nakabayashi, Nima Almassi, Chad A Reichard, Mark Pomerantz, Philip W Kantoff, Nima Sharifi
Importance: The variant HSD3B1 (1245C) allele enhances dihydrotestosterone synthesis and predicts resistance to androgen-deprivation therapy (ADT) for biochemically recurrent prostate cancer after prostatectomy and for metastatic disease. Whether this is true after radiotherapy is unknown. Objective: To determine whether the HSD3B1 (1245C) allele predicts worse clinical outcomes from ADT for biochemical recurrence after radiotherapy. Design, Setting, and Participants: The Prostate Clinical Research Information System at Dana-Farber Cancer Institute was used to identify the study cohort, which included men treated with ADT for biochemical recurrence after primary radiotherapy between 1996 and 2013...
October 12, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29049452/hsd3b1-and-response-to-a-nonsteroidal-cyp17a1-inhibitor-in-castration-resistant-prostate-cancer
#2
Nima Almassi, Chad Reichard, Jianbo Li, Carly Russell, Jaselle Perry, Charles J Ryan, Terence Friedlander, Nima Sharifi
Importance: The HSD3B1 (1245C) germline variant encodes for a gain-of-function missense in 3β-hydroxysteroid dehydrogenase isoenzyme 1 (3βHSD1) that results in increased dihydrotestosterone synthesis from extragonadal precursors and is predictive of more rapid progression to castration-resistant prostate cancer (CRPC). Objective: To determine whether the HSD3B1 (1245C) genotype is predictive of clinical response to extragonadal androgen ablation with nonsteroidal 17α-hydroxylase/17,20-lyase (CYP17A1) inhibition in men with metastatic CRPC...
October 12, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29045551/validation-of-a-metastatic-assay-using-biopsies-to-improve-risk-stratification-in-patients-with-prostate-cancer-treated-with-radical-radiation-therapy
#3
S Jain, C A Lyons, S M Walker, S McQuaid, S Hynes, D Mitchell, B Pang, G E Logan, A M McCavigan, D O'Rourke, D McArt, S McDade, I Mills, K M Prise, L A Knight, C J Steele, P W Medlow, V Berge, B Katz, D A Loblaw, D P Harkin, J James, J M O'Sullivan, R D Kennedy, D J Waugh
BackgroundRadiotherapy is an effective treatment for intermediate/high-risk locally-advanced prostate cancer, however, >30% of patients relapse within five years. Clinicopathological parameters currently fail to identify patients prone to systemic relapse and those whom treatment intensification may be beneficial. The purpose of this study was to independently validate the performance of a 70-gene Metastatic Assay in a cohort of diagnostic biopsies from patients treated with radical radiotherapy and androgen deprivation therapy (ADT)...
October 10, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29045523/the-evolution-of-chemotherapy-for-the-treatment-of-prostate-cancer
#4
D I Quinn, H M Sandler, L G Horvath, A Goldkorn, J A Eastham
Chemotherapy has been explored as a treatment option for metastatic prostate cancer since the early 1980s. Docetaxel, a taxane chemotherapeutic, was approved for the treatment of men with metastatic castration-resistant prostate cancer in 2004, and is now standard of care for late stage disease. Recent clinical studies demonstrated that patients with metastatic castration-sensitive disease, and possibly those with high-risk localized prostate cancer also benefit from docetaxel administration, expanding the role of chemotherapy in the prostate cancer treatment landscape...
July 16, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29042308/abiraterone-followed-by-enzalutamide-versus-enzalutamide-followed-by-abiraterone-in-chemotherapy-naive-patients-with-metastatic-castration-resistant-prostate-cancer
#5
Nobuaki Matsubara, Yoko Yamada, Ken-Ichi Tabata, Takefumi Satoh, Naoto Kamiya, Hiroyoshi Suzuki, Takashi Kawahara, Hiroji Uemura, Akihiro Yano, Satoru Kawakami, Masafumi Otsuka, Satoshi Fukasawa
BACKGROUND: Abiraterone (AA) and enzalutamide (ENZA) are increasingly being used in chemotherapy-naive patients with metastatic castration-resistant prostate cancer owing to efficacy and favorable toxicity. However, the order in which they should be administered has not been determined. PATIENTS AND METHODS: We retrospectively reviewed the records of chemotherapy-naive patients with metastatic castration-resistant prostate cancer who had received sequential treatment with either AA followed by ENZA (AA-ENZA) or the converse (ENZA-AA)...
September 23, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29039897/biochemical-recurrence-after-radical-prostatectomy-what-does-it-mean
#6
Rafael Tourinho-Barbosa, Victor Srougi, Igor Nunes-Silva, Mohammed Baghdadi, Gregory Rembeyo, Sophie S Eiffel, Eric Barret, Francois Rozet, Marc Galiano, Xavier Cathelineau, Rafael Sanchez-Salas
BACKGROUND: Radical prostatectomy (RP) has been used as the main primary treatment for prostate cancer (PCa) for many years with excellent oncologic results. However, approximately 20-40% of those patients has failed to RP and presented biochemical recurrence (BCR). Prostatic specific antigen (PSA) has been the pivotal tool for recurrence diagnosis, but there is no consensus about the best PSA threshold to define BCR until this moment. The natural history of BCR after surgical procedure is highly variable, but it is important to distinguish biochemical and clinical recurrence and to find the correct timing to start multimodal treatment strategy...
October 17, 2017: International Braz J Urol: Official Journal of the Brazilian Society of Urology
https://www.readbyqxmd.com/read/29037513/comparison-of-abiraterone-acetate-and-docetaxel-with-androgen-deprivation-therapy-in-high-risk-and-metastatic-hormone-na%C3%A3-ve-prostate-cancer-a-systematic-review-and-network-meta-analysis
#7
REVIEW
Christopher J D Wallis, Zachary Klaassen, Bimal Bhindi, Hanan Goldberg, Thenappan Chandrasekar, Ann M Farrell, Stephen A Boorjian, Girish S Kulkarni, Robert Jeffrey Karnes, Raj Satkunasivam
CONTEXT: Randomized clinical trials have recently examined the benefit of adding docetaxel or abiraterone to androgen deprivation therapy (ADT) in hormone-naïve advanced prostate cancer (PCa). OBJECTIVE: To perform a systematic review and network meta-analysis of randomized clinical trials, indirectly evaluating overall survival (OS) for men treated with abiraterone acetate plus prednisone/prednisolone with ADT (Abi-ADT) versus docetaxel with ADT (Doce-ADT) in hormone-naïve high-risk and metastatic PCa...
October 13, 2017: European Urology
https://www.readbyqxmd.com/read/29034790/minimal-toxicity-after-proton-beam-therapy-for-prostate-and-pelvic-nodal-irradiation-results-from-the-proton-collaborative-group-reg001-09-trial
#8
Michael D Chuong, William Hartsell, Gary Larson, Henry Tsai, George E Laramore, Carl J Rossi, J Ben Wilkinson, Adeel Kaiser, Carlos Vargas
BACKGROUND: Proton beam therapy (PBT) reduces normal organ dose compared to intensity modulated radiation therapy (IMXT) for prostate cancer patients who receive pelvic radiation therapy. It is not known whether this dosimetric advantage results in less gastrointestinal (GI) and genitourinary (GU) toxicity than would be expected from IMXT. MATERIAL AND METHODS: We evaluated treatment parameters and toxicity outcomes for non-metastatic prostate cancer patients who received pelvic radiation therapy and enrolled on the PCG REG001-09 trial...
October 14, 2017: Acta Oncologica
https://www.readbyqxmd.com/read/29032717/bet-inhibitors-in-metastatic-prostate-cancer-therapeutic-implications-and-rational-drug-combinations
#9
Mark C Markowski, Angelo M De Marzo, Emmanuel S Antonarakis
The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas Covered: We speculate that a combination approach using BET inhibition with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer...
October 16, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29030409/clinical-relevance-of-androgen-receptor-alterations-in-prostate-cancer
#10
REVIEW
Emma Jernberg, Anders Bergh, Pernilla Wikström
Prostate cancer (PC) remains a leading cause of cancer-related deaths among men worldwide, despite continuously improved treatment strategies. Patients with metastatic disease are treated by androgen deprivation therapy (ADT) that with time results in the development of castration-resistant prostate cancer (CRPC) usually established as metastases within bone tissue. The androgen receptor (AR) transcription factor is the main driver of CRPC development and of acquired resistance to drugs given for treatment of CRPC, while a minority of patients have CRPC that is non-AR driven...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29024573/targeting-mta1-hif-1%C3%AE-signaling-by-pterostilbene-in-combination-with-histone-deacetylase-inhibitor-attenuates-prostate-cancer-progression
#11
Nasir A Butt, Avinash Kumar, Swati Dhar, Agnes M Rimando, Israh Akhtar, John C Hancock, Janice M Lage, Charles R Pound, Jack R Lewin, Christian R Gomez, Anait S Levenson
The metastasis-associated protein 1(MTA1)/histone deacetylase (HDAC) unit is a cancer progression-related epigenetic regulator, which is overexpressed in hormone-refractory and metastatic prostate cancer (PCa). In our previous studies, we found a significantly increased MTA1 expression in a prostate-specific Pten-null mouse model. We also demonstrated that stilbenes, namely resveratrol and pterostilbene (Pter), affect MTA1/HDAC signaling, including deacetylation of tumor suppressors p53 and PTEN. In this study, we examined whether inhibition of MTA1/HDAC using combination of Pter and a clinically approved HDAC inhibitor, SAHA (suberoylanilide hydroxamic acid, vorinostat), which also downregulates MTA1, could block prostate tumor progression in vivo...
October 10, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/29022046/-radium-223-dichloride-in-patients-with-castration-refractory-prostate-cancer
#12
REVIEW
B M Winter, F-C von Rundstedt, M-O Grimm
Since November 2013, the alpha emitter radium-223 dichloride (Alpharadin/Xofigo®) has been approved for the treatment of men with castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. In the ASYMPCA clinical trial, radium-223 was shown to improve overall survival and to reduce the time to the first symptomatic skeletal event. The use of radium-223 was associated with a reduction of pain and an improvement of health-related quality of life compared to the placebo arm...
October 11, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/29017577/elevated-expression-of-par3-promotes-prostate-cancer-metastasis-by-forming-a-par3-apkc-kibra-complex-and-inactivating-the-hippo-pathway
#13
Pei-Jie Zhou, Wei Xue, Jinliang Peng, Yanqing Wang, Lianzi Wei, Ziqiang Yang, Helen He Zhu, Yu-Xiang Fang, Wei-Qiang Gao
BACKGROUND: Prostate cancer (PCa) is one of the most frequent tumors and leading cause of cancer deaths among males worldwide. The majority of deaths are due to recurrence and subsequent development of the metastatic cancer. Although loss or dislocalization of polarity proteins has been implicated in embryogenesis deficiency and tumorigenesis, association of polarity protein expression levels with tumor metastasis remains unclear. METHODS: Bioinformatics, qRT-PCR, western blot and immunohistochemical (IHC) analyses were used to examine expression of Par3, a key component of polarity-associated partitioning defective (PAR) complex, in primary and metastatic clinical PCa samples...
October 10, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29016954/association-of-interleukin-6-and-other-cytokines-with-self-reported-pain-in-prostate-cancer-patients-receiving-chemotherapy
#14
Sarah Al-Mazidi, Karim Farhat, TaoufiK Nedjadi, Adeel Chaudhary, Osman Zin Al-Abdin, Danny Rabah, Mohammad Al-Zoghaibi, Laiche Djouhri
Background: Pain is a common and dose-limiting side effect of many potentially curative cancer chemotherapeutic agents. This chemotherapy-induced pain (CIP) affects the quality of life of cancer patients and survivors and hampers the optimal clinical management of chemotherapy in cancer patients. The underlying mechanisms remain largely unknown, but changes in levels of cytokines/chemokines may contribute to the pathophysiology of CIP. Objective: This retrospective study was aimed at examining whether plasma levels of various cytokines change in prostate cancer patients after chemotherapy treatment and whether such changes (if any) are associated with their pain intensity...
June 22, 2017: Pain Medicine: the Official Journal of the American Academy of Pain Medicine
https://www.readbyqxmd.com/read/28986509/why-targeting-psma-is-a-game-changer-in-the-management-of-prostate-cancer-%C3%A2-a-urologist-s-point-of-view
#15
Nicholas M Donin, Robert Reiter
Prostate-specific membrane antigen (PSMA), is a transmembrane glycoprotein that is highly expressed on prostate adenocarcinomas, exhibits only limited expression in benign and extra-prostatic tissues, and thus represents an ideal target for the diagnosis and management of prostate cancer. Since its discovery over 30 years ago, significant effort has been made to develop clinical technology targeting PSMA. The last 5 years have seen an explosion of development of new agents targeting PSMA for diagnostic and therapeutic use...
October 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28983908/interventions-for-managing-medication-related-osteonecrosis-of-the-jaw
#16
REVIEW
Natalie H Beth-Tasdogan, Benjamin Mayer, Heba Hussein, Oliver Zolk
BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of cancer and osteoporosis (e.g. bisphosphonates, denosumab and antiangiogenic agents) and involves the progressive destruction of bone in the mandible or maxilla. Depending on the drug, its dosage, and the duration of exposure, the occurrence of this adverse drug reaction may be rare (e.g. following the oral administration of bisphosphonate or denosumab treatments for osteoporosis, or antiangiogenic agent-targeted cancer treatment) or common (e...
October 6, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28983763/-patients-with-metastatic-prostate-cancer-recommendations-for-primary-hormonal-or-chemohormonal-therapy
#17
REVIEW
C-H Ohlmann
The standard treatment for patients with metastatic, hormone-sensitive prostate cancer (mCSPC) has so far consisted of medical or surgical castration. However, two published clinical trials using docetaxel in combination with castration (CHAARTED and STAMPEDE) recently provided evidence for a substantial improvement in overall survival. The survival benefit was 14 and 22 months, respectively, in the two trials. In addition, the CHAARTED trial showed that patients with high-volume disease may benefit most from chemohormonal treatment...
October 5, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28977932/inhibitor-of-h3k27-demethylase-jmjd3-utx-gsk-j4-is-a-potential-therapeutic-option-for-castration-resistant-prostate-cancer
#18
Viacheslav M Morozov, Ying Li, Matthew M Clowers, Alexander M Ishov
Androgen receptor (AR) mediates initiation and progression of prostate cancer (PCa); AR-driven transcription is activated by binding of androgens to the ligand-binding domain (LBD) of AR. Androgen ablation therapy offers only a temporary relief of locally advanced and metastatic PCa, and the disease eventually recurs as a lethal castration-resistant PCa (CRPC) as there is no effective treatment for CRPC patients. Thus, it is critical to identify novel targeted and combinatorial regimens for clinical management of CRPC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28975586/impact-of-treatment-delay-in-radium-223-therapy-of-metastatic-castration-resistant-prostate-cancer-patients
#19
Marie Øbro Fosbøl, Peter Meidahl Petersen, Gedske Daugaard, Søren Holm, Andreas Kjaer, Jann Mortensen
BACKGROUND: Radium-223-dichloride (Ra-223) is an alpha-emitting, bone seeking radionuclide therapy approved for patients with metastatic castration-resistant prostate cancer (mCRPC). In the fall of 2014, a global temporary shortage of Ra-223 occurred for 2 months due to production irregularities. The aim of this study was to assess whether prolonged interval between Ra-223 cycles to non-disease related causes had a negative impact on clinical outcome of therapy. MATERIALS AND METHODS: Retrospective single-center study of mCRPC patients who initiated Ra-223 therapy in the period from March 2014 to February 2015...
October 3, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/28974120/the-oncologic-results-of-cryoablation-in-prostate-cancer-patients-with-bone-metastases
#20
Tongguo Si, Zhi Guo, Xueling Yang, Weihao Zhang, Wenge Xing
OBJECTIVE: To explore the role of whole gland cryoablation plus ADT in prostate cancer (PCa) with bone metastases compared with ADT treatment alone in metastatic PCa. METHODS: A total of 30 patients with biopsy proven PCa with bone metastases underwent cryoablation and ADT treatment. The control group consisted of 30 men who were initially treated with ADT only and who were followed until progression, development of castration resistant PCa or death. Patients were pair-matched for age, PSA level, clinical stage, preoperative biopsy Gleason score, and bone metastases...
October 4, 2017: International Journal of Hyperthermia
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