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Treatment resistant mCRPC

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https://www.readbyqxmd.com/read/29340285/quantitative-bone-scan-lesion-area-as-an-early-surrogate-outcome-measure-indicative-of-overall-survival-in-metastatic-prostate-cancer
#1
Matthew S Brown, Grace Hyun J Kim, Gregory H Chu, Bharath Ramakrishna, Martin Allen-Auerbach, Cheryce P Fischer, Benjamin Levine, Pawan K Gupta, Christiaan W Schiepers, Jonathan G Goldin
A clinical validation of the bone scan lesion area (BSLA) as a quantitative imaging biomarker was performed in metastatic castration-resistant prostate cancer (mCRPC). BSLA was computed from whole-body bone scintigraphy at baseline and week 12 posttreatment in a cohort of 198 mCRPC subjects (127 treated and 71 placebo) from a clinical trial involving a different drug from the initial biomarker development. BSLA computation involved automated image normalization, lesion segmentation, and summation of the total area of segmented lesions on bone scan AP and PA views as a measure of tumor burden...
January 2018: Journal of Medical Imaging
https://www.readbyqxmd.com/read/29340049/pharmacological-treatment-with-inhibitors-of-nuclear-export-enhances-the-antitumor-activity-of-docetaxel-in-human-prostate-cancer
#2
Giovanni Luca Gravina, Andrea Mancini, Alessandro Colapietro, Francesco Marampon, Roberta Sferra, Simona Pompili, Leda Assunta Biordi, Roberto Iorio, Vincenzo Flati, Christian Argueta, Yosef Landesman, Michael Kauffman, Sharon Shacham, Claudio Festuccia
Background and aims: Docetaxel (DTX) modestly increases patient survival of metastatic castration-resistant prostate cancer (mCRPC) due to insurgence of pharmacological resistance. Deregulation of Chromosome Region Maintenance (CRM-1)/ exportin-1 (XPO-1)-mediated nuclear export may play a crucial role in this phenomenon. Material and methods: Here, we evaluated the effects of two Selective Inhibitor of Nuclear Export (SINE) compounds, selinexor (KPT-330) and KPT-251, in association with DTX by using 22rv1, PC3 and DU145 cell lines with their...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29331381/clinical-outcomes-of-first-line-abiraterone-acetate-or-enzalutamide-for-metastatic-castration-resistant-prostate-cancer-after-androgen-deprivation-therapy%C3%A2-docetaxel-or-adt-alone-for-metastatic-hormone-sensitive-prostate-cancer
#3
Edoardo Francini, Steven Yip, Shubidito Ahmed, Haocheng Li, Luke Ardolino, Carolyn P Evan, Marina Kaymakcalan, Grace K Shaw, Philip W Kantoff, Mary-Ellen Taplin, Nimira S Alimohamed, Anthony M Joshua, Daniel Y C Heng, Christopher J Sweeney
BACKGROUND: The CHAARTED (ChemoHormonal Therapy Versus Androgen Ablation Randomized Trial for Extensive Disease in Prostate Cancer) and STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trials showed that the addition of docetaxel (D) to androgen deprivation therapy (ADT) prolonged longevity of men with metastatic hormone-sensitive prostate cancer (mHSPC). However, the impact of upfront D on subsequent therapies is still unexplored. As abiraterone acetate (AA) and enzalutamide (E) are the most commonly used first-line treatment for metastatic castration-resistant prostate cancer (mCRPC), we aimed to assess whether they maintained their efficacy after ADT+D versus ADT alone...
December 27, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29326358/targeted-alpha-therapy-of-mcrpc-with-225actinium-psma-617-swimmer-plot-analysis-suggests-efficacy-regarding-duration-of-tumor-control
#4
Clemens Kratochwil, Frank Bruchertseifer, Hendrik Rathke, Markus Hohenfellner, Frederik L Giesel, Uwe Haberkorn, Alfred Morgenstern
The aim of this evaluation is to identify first indicators regarding the efficacy of 225Ac-PSMA-617 therapy in a retrospectively analyzed group of patients. Methods: Forty patients with metastatic castration-resistant prostate cancer were selected for treatment with 3 cycles of 100 kBq/kgBW 225Ac-PSMA-617 in 2 months intervals. Prostate-specific antigen (PSA) and blood cell count were measured every 4 weeks. Prostate-specific membrane antigen (PSMA)-PET/CT or PSMA-SPECT/CT were used for baseline staging and imaging follow-up at month six...
January 11, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/29319382/ctc-derived-ar-v7-detection-as-a-prognostic-and-predictive-biomarker-in-advanced-prostate-cancer
#5
Diogo A Bastos, Emmanuel S Antonarakis
Prostate cancer is a highly heterogeneous disease, with remarkably different prognosis across all stages. Increased circulating tumor cell (CTC) count (≥ 5) using the CellSearch assay has been identified as one of the markers that can be used to predict survival, with added value beyond currently available prognostic factors. Recently, androgen receptor splice variant 7 (AR-V7) detection has been associated with worse outcomes for patients with castration-resistant prostate cancer (CRPC) treated with novel androgen receptor-signaling (ARS) inhibitors such as abiraterone and enzalutamide but not taxane chemotherapies...
January 10, 2018: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/29318740/risk-of-febrile-neutropenia-and-early-treatment-cessation-in-men-receiving-standard-and-dose-reduced-3-weekly-docetaxel-for-metastatic-castration-resistant-prostate-cancer
#6
Anis A Hamid, Kaspar Willson, Andrew D Vincent, Babak Tamjid, Margaret Lee, Alice Bergin, Chun Gan, Ainsley Campbell, Josephine Stewart, Carmel Pezaro, Ben Tran, Andrew J Weickhardt
BACKGROUND: Docetaxel is an effective therapy for metastatic castration-resistant prostate cancer (mCRPC); however, many patients experience febrile neutropenia (FN) and cease treatment early due to toxicity. It is not known whether lower dose (LD) q3-weekly docetaxel impacts toxicity or efficacy. METHODS: Multicenter retrospective study included 166 patients with mCRPC who received q3-weekly docetaxel between 2010 and 2015. Demographic, disease, chemotherapy (standard dose, SD>60 mg/m2 vs LD≤60 mg/m2 ) and toxicity data were collected...
January 10, 2018: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29298991/current-approaches-to-incorporation-of-radium-223-in-clinical-practice
#7
REVIEW
Chris Parker, Axel Heidenreich, Sten Nilsson, Neal Shore
BACKGROUND: Treatment options for metastatic castration-resistant prostate cancer (mCRPC) have expanded in recent years and include cytotoxic agents (e.g., docetaxel and cabazitaxel), immunotherapy (e.g., sipuleucel-T), oral hormonal therapies targeting the androgen receptor axis (e.g., enzalutamide and abiraterone), and targeted alpha therapy (e.g., radium-223 dichloride (radium-223)). Although treatment guidelines have been updated to reflect the availability of new agents, it is not easy to apply them in daily clinical practice because recommendations vary depending on patient comorbidities and disease characteristics...
January 3, 2018: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/29290963/prognostic-factors-in-men-with-metastatic-castration-resistant-prostate-cancer-treated-with-cabazitaxel
#8
Bodine P S Belderbos, Ronald de Wit, Esther Oomen-de Hoop, Annemieke Nieuweboer, Paul Hamberg, Robbert J van Alphen, André Bergman, Nelly van der Meer, Sander Bins, Ron H J Mathijssen, Robert J van Soest
Background: Treatment selection for men with metastatic castration-resistant prostate cancer (mCRPC) has become increasingly challenging with the introduction of novel therapies at earlier disease stages. The purpose of this study was to identify prognostic factors for overall survival (OS) and PSA response in patients with mCRPC treated with cabazitaxel. Results: 224 mCRPC patients were included in the current analysis. In multivariable analysis, WHO performance status, baseline hemoglobin, alkaline phosphatase and albumin were all significantly associated with OS...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29286483/serum-and-plasma-copy-number-detection-using-real-time-pcr
#9
Samanta Salvi, Vincenza Conteduca, Filippo Martignano, Giorgia Gurioli, Daniele Calistri, Valentina Casadio
Serum and plasma cell free DNA (cfDNA) has been shown as an informative, non-invasive source of biomarkers for cancer diagnosis, prognosis, monitoring, and prediction of treatment resistance. Starting from the hypothesis that androgen receptor (AR) gene copy number (CN) gain is a frequent event in metastatic castration resistance prostate cancer (mCRPC), we propose to analyze this event in cfDNA as a potential predictive biomarker. We evaluated AR CN in cfDNA using 2 different real-time PCR assays and 2 reference genes (RNaseP and AGO1)...
December 15, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29285775/systemic-immune-inflammation-index-predicts-the-combined-clinical-outcome-after-sequential-therapy-with-abiraterone-and-docetaxel-for-metastatic-castration-resistant-prostate-cancer-patients
#10
Liancheng Fan, Rui Wang, Chenfei Chi, Wen Cai, Yong Zhang, Hongyang Qian, Xiaoguang Shao, Yanqing Wang, Fan Xu, Jiahua Pan, Yinjie Zhu, Xun Shangguan, Lixin Zhou, Baijun Dong, Wei Xue
OBJECTIVE: To compare the antitumor effect of abiraterone (AA) followed by docetaxel-prednisone (DP) or vice versa in metastatic castration-resistant prostate cancer (mCRPC) patients, and explored factors that might predict combined PSA-PFS, combined rPFS and OS. PATIENTS AND METHODS: We retrospectively analyzed mCRPC patients treated with sequential therapy using DP followed by AA or vice versa. Patients who had received enzalutamide or cabazitaxel were excluded...
December 29, 2017: Prostate
https://www.readbyqxmd.com/read/29285670/a-3-variable-prognostic-score-3-ps-for-overall-survival-prediction-in-metastatic-castration-resistant-prostate-cancer-treated-with-223radium-dichloride
#11
Viviana Frantellizzi, Alessio Farcomeni, Giulia Anna Follacchio, Massimiliano Pacilio, Rosanna Pellegrini, Roberto Pani, Giuseppe De Vincentis
OBJECTIVE: In mCRPC patients treated with 223Ra, a major issue is the validation of reliable prognostic and predictive biomarkers to maximize clinical benefit and minimize toxicities and costs. Bearing in mind how changes in tALP did not meet statistical requirements as surrogate marker for survival, aim of this single-center retrospective study was to characterize the prognostic and predictive role of baseline clinical variables associated with overall survival in patients receiving 223Ra treatment...
December 28, 2017: Annals of Nuclear Medicine
https://www.readbyqxmd.com/read/29275833/efficacy-against-human-prostate-cancer-by-prostate-specific-membrane-antigen-specific-transforming-growth-factor-%C3%AE-insensitive-genetically-targeted-cd8-t-cells-derived-from-patients-with-metastatic-castrate-resistant-disease
#12
Qiang Zhang, Brian T Helfand, Benedito A Carneiro, Weijun Qin, Ximing J Yang, Chung Lee, Weipeng Zhang, Francis J Giles, Massimo Cristofanilli, Timothy M Kuzel
Current immunotherapy has limited efficacy on metastatic castrate-resistant prostate cancer (mCRPC). We therefore sought to improve the antitumor ability of mCRPC patient-derived CD8+ T-cells by the endowment of specificity to prostate-specific membrane antigen (PSMA) and insensitivity to immunosuppressant molecule transforming growth factor-β (TGF-ß) under the control of herpes simplex virus-1 thymidine kinase. CD8+ T-cells were collected by leukapheresis and cultured in a Food and Drug Administration-approved Cell Processing Work Station...
December 21, 2017: European Urology
https://www.readbyqxmd.com/read/29275145/taxane-based-combination-therapies-for-metastatic-prostate-cancer
#13
REVIEW
Paul G Corn, Neeraj Agarwal, John Charles Araujo, Guru Sonpavde
CONTEXT: Multiple single-agent therapies improving survival are approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC), including two chemotherapies, two androgen-signaling axis-targeting agents, an immunotherapeutic vaccine, and a radiopharmaceutical. Combination therapy can target multiple oncogenic pathways simultaneously, while potentially curbing the development of treatment resistance. OBJECTIVE: To provide a succinct overview of taxane-based combination therapies currently being evaluated for the treatment of metastatic prostate cancer...
December 20, 2017: European Urology Focus
https://www.readbyqxmd.com/read/29274813/comparison-of-alternative-androgen-receptor-axis-targeted-agent-arata-and-docetaxel-as-second-line-therapy-for-patients-with-metastatic-castration-resistant-prostate-cancer-with-progression-after-initial-arata-in-real-world-clinical-practice-in-japan
#14
Hideaki Miyake, Takayuki Sugiyama, Ryota Aki, Yuto Matsushita, Keita Tamura, Daisuke Motoyama, Toshiki Ito, Atsushi Otsuka
BACKGROUND: The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor-axis-targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA-to-Enz, n = 49; Enz-to-AA, n = 59) and 114 received docetaxel (DTX; AA-to-DTX, n = 54; Enz-to-DTX, n = 60)...
December 6, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29248429/predicting-therapy-response-and-resistance-in-metastatic-prostate-cancer-with-circulating-tumor-dna
#15
REVIEW
Elie Ritch, Alexander W Wyatt
The treatment of metastatic castration-resistant prostate cancer (mCRPC) is empirical, with progress to a more precision medicine approach hampered by lack of predictive biomarkers. This is due in large part to the historical difficulty of molecularly profiling a bone-predominant metastatic disease. Focus has turned to minimally invasive sources of tumor material to better understand the molecular drivers of therapy resistance. Circulating cell-free tumor DNA (ctDNA) is highly abundant in the bloodstream of mCRPC patients and appears to provide an accurate snapshot of real-time tumor genomics...
December 13, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/29247284/third-line-treatment-and-177lu-psma-radioligand-therapy-of-metastatic-castration-resistant-prostate-cancer-a-systematic-review
#16
REVIEW
Finn Edler von Eyben, Giandomenico Roviello, Timo Kiljunen, Christian Uprimny, Irene Virgolini, Kalevi Kairemo, Timo Joensuu
AIMS: There is a controversy as to the relative efficacy of 177Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). METHODS: The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines...
December 16, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29237083/relationship-between-patient-reported-outcomes-and-clinical-outcomes-in-metastatic-castration-resistant-prostate-cancer-post-hoc-analysis-of-cou-aa-301-and-cou-aa-302
#17
D Cella, S Traina, T Li, K Johnson, K F Ho, A Molina, N D Shore
Background: Patient-reported outcomes (PROs) are used to assess benefit-risk in drug development. The relationship between PROs and clinical outcomes is not well understood. We aimed to elucidate the relationships between changes in PRO measures and clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC). Patients and methods: We investigated relationships between changes in self-reported fatigue, pain, functional well-being (FWB), physical well-being (PWB) and prostate cancer-specific symptoms with overall survival (OS) and radiographic progression-free survival (rPFS) after 6 and 12 months of treatment in COU-AA-301 (N = 1195) or COU-AA-302 (N = 1088)...
December 11, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29222530/seizure-rates-in-enzalutamide-treated-men-with-metastatic-castration-resistant-prostate-cancer-and-risk-of-seizure-the-upward-study
#18
Susan Slovin, William Clark, Joan Carles, Andrew Krivoshik, Jung Wook Park, Fong Wang, Daniel George
Importance: The androgen receptor inhibitor enzalutamide prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). In controlled clinical studies, 0.5% (10 of 2051) of patients experienced seizure, but patients with a history of or risk factors for seizure were excluded. Men with mCRPC and seizure risk factors have an estimated seizure rate of 2.8 per 100 patient-years without enzalutamide exposure. Objective: To assess seizure incidence in patients with seizure risk factors who were receiving enzalutamide for mCRPC...
December 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29191639/population-based-analysis-of-treatment-toxicity-among-men-with-castration-resistant-prostate-cancer-a-phase-iv-study
#19
Christopher J D Wallis, Raj Satkunasivam, Refik Saskin, Symron Bansal, Girish S Kulkarni, Urban Emmenegger, Robert K Nam
OBJECTIVE: To assess the toxicity and effectiveness of contemporary metastatic castrate-resistant prostate cancer (mCRPC) treatments at a population-level, among all patients in Ontario particularly treated with newer agents including abiraterone, enzalutamide, docetaxel and cabazitaxel. METHODS: We performed a population-based, retrospective cohort study of 2439 men aged ≥65 years treated for mCRPC with abiraterone, enzalutamide, docetaxel, or cabazitaxel from 2003-2015 in Ontario, Canada...
November 27, 2017: Urology
https://www.readbyqxmd.com/read/29187435/evaluating-metformin-as-a-potential-chemosensitizing-agent-when-combined-with-docetaxel-chemotherapy-in-castration-resistant-prostate-cancer-cells
#20
Michelle J Mayer, Laurence H Klotz, Vasundara Venkateswaran
BACKGROUND/AIM: Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining docetaxel with a chemosensitizing agent. We hypothesized that metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC cells. MATERIALS AND METHODS: MTS assays were used to determine the effect of metformin-docetaxel treatment on PC3 and DU145 cell viability...
December 2017: Anticancer Research
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