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Kambiz Rahbar, Hojjat Ahmadzadehfar, Clemens Kratochwil, Uwe Haberkorn, Michael Schäfers, Markus Essler, Richard P Baum, Harshad R Kulkarani, Matthias Schmidt, Peter Bartenstein, Andreas Pfestroff, Ulf Lützen, Marlies Marx, Vikas Prasad, Winfried Brenner, Alexander Heinzel, Juri Ruf, Philipp Tobias Meyer, Martin Heuschkel, Maria Eveslage, Martin Bögemann, Wolfgang Peter Fendler, Bernd Joachim Krause
: (177)Lutetium labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of (177)Lu-PSMA-617 in a large cohort of patients. METHODS: 145 patients (median age 73 years, range 43-88) with mCRPC were treated with (177)Lu-PSMA-617 in 12 therapy centres between February 2014 and July 2015 with one to four therapy cycles and an activity range of 2 to 8 GBq per cycle...
October 20, 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Silvana Giacinti, Paolo Carlini, Michela Roberto, Maria Bassanelli, Lidia Strigari, Francesco Pavese, Anna M Aschelter, Alessandra Felici, Maurizio Valeriani, Francesco Cognetti, Paolo Marchetti
Abiraterone acetate (AA) demonstrated its efficacy in the treatment of patients with metastatic castration resistance prostate cancer (mCRPC) in predocetaxel and postdocetaxel setting. However, we learn from pivotal studies that forms of primary and acquired resistance to this drug exist. Patient selection becomes so crucial to optimize treatment results. Potential predictive biomarkers have been identified but are not yet validated. In this scenario, clinical features and disease characteristics may still be of value in selecting patients for different treatments...
October 19, 2016: Anti-cancer Drugs
Claire Levrier, Martin C Sadowski, Anja Rockstroh, Brian Gabrielli, Maria Kavallaris, Melanie Lehman, Rohan A Davis, Colleen C Nelson
The lack of a cure for metastatic castrate-resistant prostate cancer (mCRPC) highlights the urgent need for more efficient drugs to fight this disease. Here, we report the mechanism of action of the natural product 6α-acetoxyanopterine (6-AA) in prostate cancer cells. At low nanomolar doses, this potent cytotoxic alkaloid from the Australian endemic tree Anopterus macleayanus induced a strong accumulation of LNCaP and PC-3 (prostate cancer) cells as well as HeLa (cervical cancer) cells in mitosis, severe mitotic spindle defects and asymmetric cell divisions, ultimately leading to mitotic catastrophe accompanied by cell death through apoptosis...
October 19, 2016: Molecular Cancer Therapeutics
Shabbir M H Alibhai, Salman Aziz, Tharsika Manokumar, Narhari Timilshina, Henriette Breunis
OBJECTIVE: Since the benefits of chemotherapy in treating older men with metastatic castration-resistant prostate cancer (mCRPC) are modest, validated tools that predict the risk of treatment toxicity may aid clinical decision-making. Whether these tools are better than oncologist judgment remains unclear. We compared the Cancer and Aging Research Group (CARG) tool, the Vulnerable Elders Survey-13 (VES-13), and oncologist judgment in predicting toxicity in men with mCRPC undergoing chemotherapy...
October 15, 2016: Journal of Geriatric Oncology
Yoko Yamada, Nobuaki Matsubara, Ken-Ichi Tabata, Takefumi Satoh, Naoto Kamiya, Hiroyoshi Suzuki, Takashi Kawahara, Hiroji Uemura, Akihiro Yano, Satoru Kawakami
BACKGROUND: Both abiraterone acetate (AA) and enzalutamide are promising agents for patients with pre- and post-chemotherapy metastatic castration-resistant prostate cancer (mCRPC). Several retrospective analysis suggested clinical cross-resistance between these agents in patients previously treated with docetaxel. However, data on the antitumor activity of AA as a second androgen receptor-targeting new agent after the failure of enzalutamide in chemotherapy-naive mCRPC patients is unavailable...
October 18, 2016: BMC Research Notes
Zachery R Reichert, Maha Hussain
The development of metastatic castration-resistant prostate cancer (mCRPC) signals the terminal disease phase. The preceding hormone-dependent disease setting is effectively managed with androgen deprivation therapy. This foundation of treatment has a high rate of biochemical and clinical response and meaningful clinical benefit but is finite in duration as most cancers will progress to castration resistance. Historically, treatment for mCRPC entailed androgen receptor (AR) inhibitors (nilutamide, flutamide, bicalutamide), nonspecific steroidal biosynthesis inhibitors (ketoconazole, itraconazole), steroids (prednisone, diethylstilbesterol, dexamethasone), or palliative chemotherapy (mitoxantrone, estramustine), but none of these strategies impacted survival...
September 2016: Cancer Journal
Che-Kai Tsao, John Sfakianos, Bobby Liaw, Kiev Gimpel-Tetra, Margaret Kemeny, Linda Bulone, Mohammad Shahin, William Kyu Oh, Matthew David Galsky
LESSONS LEARNED: The safety and activity findings of abiraterone acetate plus prednisone treatment in black men with mCRPC were similar to results from previously conducted studies with largely white populations.Poor trial accrual continues to be a challenge in black men with mCRPC and further efforts are needed to address such underrepresentation. BACKGROUND: Self-identified black men have higher incidence and mortality from prostate cancer in the United States compared with white men but are dramatically underrepresented in clinical trials exploring novel therapies for metastatic castration-resistant prostate cancer (mCRPC)...
October 14, 2016: Oncologist
Jesse Aidan Dinh, Danial Baker, Manpreet Chahal
OBJECTIVE: To provide an overview of the efficacy, tolerability, drug interactions, dosing, and administration issues associated with enzalutamide, abiraterone, and radium-223 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). DATA SOURCES: MEDLINE and Web of Science were used to search for relevant articles using a key-word search (enzalutamide, abiraterone, radium-223, and phase 3). No restriction was placed on the date of publication...
2016: Consultant Pharmacist: the Journal of the American Society of Consultant Pharmacists
Vanita Noronha, Amit Joshi, Vamshi Krishna Muddu, Vijay Maruti Patil, Kumar Prabhash
<bold>Objective:</bold> To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. <bold>Methods:</bold> mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported...
May 2016: Case Reports in Oncology
Pradeep S Jadhavar, Sreekanth A Ramachandran, Eduardo Riquelme, Ashu Gupta, Kevin P Quinn, Devleena Shivakumar, Soumya Ray, Dnyaneshwar Zende, Anjan K Nayak, Sandeep K Miglani, Balaji D Sathe, Mohd Raja, Olivia Farias, Ivan Alfaro, Sebastián Belmar, Javier Guerrero, Sebastián Bernales, Sarvajit Chakravarty, David T Hung, Jeffrey N Lindquist, Roopa Rai
While enzalutamide and abiraterone are approved for treatment of metastatic castration-resistant prostate cancer (mCRPC), approximately 20-40% of patients have no response to these agents. It has been stipulated that the lack of response and the development of secondary resistance to these drugs may be due to the presence of AR splice variants. HDAC6 has a role in regulating the androgen receptor (AR) by modulating heat shock protein 90 (Hsp90) acetylation, which controls the nuclear localization and activation of the AR in androgen-dependent and independent scenarios...
October 4, 2016: Bioorganic & Medicinal Chemistry Letters
Sebastien J Hotte
Despite the significant survival benefit of taxane therapy in metastatic castration-resistant prostate cancer (mCRPC), all patients inevitably develop treatment resistance. An understanding of resistance mechanisms has led to new therapies for prostate cancer (cabazitaxel, abiraterone and enzalutamide), all of which have improved survival following first-line docetaxel. Another treatment, currently in development, targets the prosurvival molecule clusterin. Custirsen, an antisense molecule that inhibits clusterin production, has shown promise in combination with docetaxel in mCRPC patients at risk for poor outcomes...
October 7, 2016: Future Oncology
Peter Kuhn, Anders Carlsson, Madelyn S Luttgen, Kevin Keomanee Dizon, Patricia Troncoso, Paul Corn, Anand Kolatkar, James B Hicks, Christopher Logothetis, Amado J Zurita
PURPOSE: Recent studies demonstrate that prostate cancer clones from different metastatic sites are dynamically represented in the blood of patients over time, suggesting that the paired evaluation of tumor cells in circulation and bone marrow, the primary target for prostate cancer metastasis, may provide complementary information. EXPERIMENTAL DESIGN: We adapted our single-cell high-content liquid biopsy platform to bone marrow aspirates (BMA), to concurrently identify and characterize prostate cancer cells in patients' blood and bone and thus discern features associated to tumorigenicity and dynamics of metastatic progression...
October 4, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
T Uo, H Dvinge, C C Sprenger, R K Bradley, P S Nelson, S R Plymate
The presence of intact ligand-binding domain (LBD) ensures the strict androgen-dependent regulation of androgen receptor (AR): binding of androgen induces structural reorganization of LBD resulting in release of AR from HSP90, suppression of nuclear export which otherwise dominates over import and nuclear translocation of AR as a transcription factor. Thus, loss or defects of the LBD abolish constraint from un-liganded LBD as exemplified by constitutively active AR variants (AR-Vs), which are associated with emerging resistance mechanism to anti-AR therapy in castration-resistant prostate cancer (mCRPC)...
October 3, 2016: Oncogene
Harshad R Kulkarni, Aviral Singh, Christiane Schuchardt, Karin Niepsch, Manal Sayeg, Yevgeniy Leshch, Hans-Juergen Wester, Richard P Baum
A potential milestone in personalized nuclear medicine is theranostics of metastatic castration-resistant prostate cancer (mCRPC) based on molecular imaging using PET/CT with (68)Ga-labeled prostate-specific membrane antigen (PSMA) ligands and molecular radiotherapy using PSMA-targeted radioligand therapy (PRLT) with (177)Lu-PSMA ligands. (68)Ga-PSMA PET/CT enables accurate detection of mCRPC lesions with high diagnostic sensitivity and specificity and provides quantitative and reproducible data that can be used to select patients for PRLT and therapeutic monitoring...
October 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Neeta Pandit-Taskar, Darren R Veach, Josef J Fox, Howard I Scher, Michael J Morris, Steven M Larson
Castration-resistant prostate cancer (CRPC) is the lethal form of prostate cancer, and more than 26,000 men will die from this disease in 2016. The pathophysiology of CRPC is clearly multifactorial, but most often, androgen receptor (AR) upregulation is associated with its earliest beginnings and the AR increase is part of the multimolecular complex including downstream effector proteins linked to AR (AR-axis) responsible for rapid proliferation and malignant features of the malignant cell. In both animal models and patients, glycolysis (Warburg effect) is also an early manifestation of CRPC transformation...
October 2016: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Daniel M Moreira, Lauren E Howard, Katharine N Sourbeer, Hiruni S Amarasekara, Lydia C Chow, Dillon C Cockrell, Connor L Pratson, Brian T Hanyok, William J Aronson, Christopher J Kane, Martha K Terris, Christopher L Amling, Matthew R Cooperberg, Stephen J Freedland
OBJECTIVE: To identify the predictors of time from initial diagnosis of metastatic castration-resistance prostate cancer (mCRPC) to all-cause death within the Shared Equal Access Regional Cancer Hospital cohort. PATIENTS AND METHODS: We performed a retrospective analysis of 205 mCRPC men. Overall survival was estimated and plotted using the Kaplan-Meier method. The uni- and multivariable overall survival predictors were evaluated with the Cox proportional hazards model...
August 31, 2016: Clinical Genitourinary Cancer
Per Kongsted, Inge Marie Svane, Henriette Lindberg, Lisa Sengeløv
BACKGROUND: We investigated the impact of the number of docetaxel cycles administered in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line chemotherapy. PATIENTS AND METHODS: Charts from 421 consecutive patients who initiated standard treatment with docetaxel-based chemotherapy (75 mg/m(2) every 3 weeks) between 2007 and 2013 were reviewed. Patients who received < 6 cycles of docetaxel were excluded from the analysis...
September 8, 2016: Clinical Genitourinary Cancer
Wolfgang P Fendler, Svenja Reinhardt, Harun Ilhan, Andreas Delker, Guido Böning, Franz J Gildehaus, Christian Stief, Peter Bartenstein, Christian Gratzke, Sebastian Lehner, Axel Rominger
Prostate cancer can be targeted by ligands to the prostate-specific membrane antigen (PSMA). We aimed to evaluate dosimetry, safety and efficacy of 177Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC).Fifteen patients each received two cycles of 3.7 GBq (n = 5) or 6.0 GBq (n = 10) 177Lu-PSMA-617 at an eight to ten weeks interval. For safety monitoring, each treatment was followed by dosimetry with serial quantitative SPECT as well as inpatient and outpatient recording of adverse events...
September 24, 2016: Oncotarget
K Miller, J Gschwend, J-M Wolff
At present, abiraterone acetate and enzalutamide are the most commonly used substances in the first-line treatment of asymptomatic or mildly symptomatic metastatic castration-resistant prostate carcinoma (mCRPC). Since the relevant pivotal trials have demonstrated comparable clinical efficacy for both substances, further factors should be considered for the choice of treatment. As mCRPC patients usually receive several lines of treatment, different adaptation and resistance mechanisms leading to treatment failure could be important...
September 2016: Aktuelle Urologie
Glenn Heller, Karim Fizazi, Robert T McCormack, Arturo Molina, David MacLean, Iain J Webb, Fred Saad, Johann S de Bono, Howard I Scher
PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease for which better prognostic models for survival are needed. We examined the added value of circulating tumor cell (CTC) enumeration relative to common prognostic laboratory measures from CRPC patients. Experimental Technique: Utility of CTC enumeration as a baseline and postbaseline prognostic biomarker was examined using data from two prospective randomized registration-directed trials (COU-AA-301 and ELM-PC4) within statistical models used to estimate risk for survival...
September 27, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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