late-stage mCRPC

Fadi Khreish, Niklas Ebert, Martin Ries, Stephan Maus, Florian Rosar, Hendrik Bohnenberger, Tobias Stemler, Matthias Saar, Mark Bartholomä, Samer Ezziddin
PURPOSE: Up to 30% of patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) never respond or develop resistance to 177 Lu-labeled PSMA-targeted radioligand monotherapy. Single-agent PSMA-targeted radioligand therapy (PRLT) with the alpha-emitter 225 Ac showed promise against mCRPC but may cause severe and/or persistent xerostomia, which may substantially impair patients' quality-of-life. We hypothesized that when 177 Lu-PSMA ligand alone is ineffective, tandem therapy with low-activity 225 Ac-PSMA ligand plus full activity of the beta emitter may enhance efficacy while minimizing xerostomia severity...
November 22, 2019: European Journal of Nuclear Medicine and Molecular Imaging
Keisuke Shigeta, Takeo Kosaka, Hiroshi Hongo, Yoshinori Yanai, Kazuhiro Matsumoto, Shinya Morita, Ryuichi Mizuno, Toshiaki Shinojima, Eiji Kikuchi, Mototsugu Oya
BACKGROUND: Our specific aim was to investigate the prognostic value of effective duration of first androgen deprivation therapy (ADT) and to evaluate the clinical impact on early docetaxel administration with oncological outcomes in castration-resistant prostate cancer (CRPC) patients treated with docetaxel. METHODS: We identified 148 mCRPC patients who were treated with 75 mg/m2 docetaxel. We defined 16 months as the threshold for the effective duration of ADT, and defined 12 months as the cut-off time for starting docetaxel from the onset of CRPC...
January 2, 2019: International Journal of Clinical Oncology
Matthias M Heck, Robert Tauber, Sebastian Schwaiger, Margitta Retz, Calogero D'Alessandria, Tobias Maurer, Andrei Gafita, Hans-Jürgen Wester, Jürgen E Gschwend, Wolfgang A Weber, Markus Schwaiger, Karina Knorr, Matthias Eiber
Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly being used in metastatic castration-resistant prostate cancer (mCRPC). The objective of this study is to report our clinical experience with RLT using 177-lutetium-labeled PSMA-I&T. A total of 100 patients were treated under a compassionate use protocol with a total number of 319 cycles (median two cycles, range 1-6). Eligibility criteria included previous treatment with abiraterone or enzalutamide, previous taxane-based chemotherapy or chemoineligibility, and positive PSMA-ligand uptake at positron-emission tomography scan...
November 22, 2018: European Urology
Varune Rohan Ramnarine, Mohammed Alshalalfa, Fan Mo, Noushin Nabavi, Nicholas Erho, Mandeep Takhar, Robert Shukin, Sonal Brahmbhatt, Alexander Gawronski, Maxim Kobelev, Mannan Nouri, Dong Lin, Harrison Tsai, Tamara L Lotan, R Jefferey Karnes, Mark A Rubin, Amina Zoubeidi, Martin E Gleave, Cenk Sahinalp, Alexander W Wyatt, Stanislav V Volik, Himisha Beltran, Elai Davicioni, Yuzhuo Wang, Colin C Collins
Background: Treatment-induced neuroendocrine prostate cancer (tNEPC) is an aggressive variant of late-stage metastatic castrate-resistant prostate cancer that commonly arises through neuroendocrine transdifferentiation (NEtD). Treatment options are limited, ineffective, and, for most patients, result in death in less than a year. We previously developed a first-in-field patient-derived xenograft (PDX) model of NEtD. Longitudinal deep transcriptome profiling of this model enabled monitoring of dynamic transcriptional changes during NEtD and in the context of androgen deprivation...
June 1, 2018: GigaScience
Ming Chen, Pier Paolo Pandolfi
Men who develop metastatic castration-resistant prostate cancer (mCRPC) will invariably succumb to their disease. Thus there remains a pressing need for preclinical testing of new drugs and drug combinations for late-stage prostate cancer (PCa). Insights from the mCRPC genomic landscape have revealed that, in addition to sustained androgen receptor (AR) signaling, there are other actionable molecular alterations and distinct molecular subclasses of PCa; however, the rate at which this knowledge translates into patient care via current preclinical testing is painfully slow and inefficient...
April 2, 2018: Cold Spring Harbor Perspectives in Medicine
Marie Øbro Fosbøl, Peter Meidahl Petersen, Andreas Kjaer, Jann Mortensen
The aim of this study was to investigate the prognostic value of the quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index [BSI]) in patients who have advanced metastatic castration-resistant prostate cancer (mCRPC) and are receiving 223 RaCl2 We hypothesized that the BSI can serve as a prognostic biomarker of overall survival (OS) and hematologic toxicity and as a tool for response assessment in patients with mCRPC treated with 223 RaCl2 Methods: This study was a retrospective investigation of a Danish cohort of mCRPC patients who received 223 RaCl2 therapy between March 2014 and October 2015 and for whom baseline bone scintigraphy was available...
April 2018: Journal of Nuclear Medicine
Jordan O'Malley, Rahul Kumar, Andrey N Kuzmin, Artem Pliss, Neelu Yadav, Srimmitha Balachandar, Jianmin Wang, Kristopher Attwood, Paras N Prasad, Dhyan Chandra
Metastatic castration-resistant prostate cancer (mCRPC) remains incurable and is one of the leading causes of cancer-related death among American men. Therefore, detection of prostate cancer (PCa) at early stages may reduce PCa-related mortality in men. We show that lipid quantification by vibrational Raman Microspectroscopy and Biomolecular Component Analysis may serve as a potential biomarker in PCa. Transcript levels of lipogenic genes including sterol regulatory element-binding protein-1 (SREBP-1) and its downstream effector fatty acid synthase (FASN), and rate-limiting enzyme acetyl CoA carboxylase (ACACA) were upregulated corresponding to both Gleason score and pathologic T stage in the PRAD TCGA cohort...
July 1, 2017: Cancer Letters
Christopher R Heery, Ravi A Madan, Mark N Stein, Walter M Stadler, Robert S Di Paola, Myrna Rauckhorst, Seth M Steinberg, Jennifer L Marté, Clara C Chen, Italia Grenga, Renee N Donahue, Caroline Jochems, William L Dahut, Jeffrey Schlom, James L Gulley
PSA-TRICOM is a therapeutic vaccine in late stage clinical testing in metastatic castration-resistant prostate cancer (mCRPC). Samarium-153-ethylene diamine tetramethylene phosphonate (Sm-153-EDTMP; Quadramet®), a radiopharmaceutical, binds osteoblastic bone lesions and emits beta particles causing local tumor cell destruction. Preclinically, Sm-153-EDTMP alters tumor cell phenotype facilitating immune-mediated killing. This phase 2 multi-center trial randomized patients to Sm-153-EDTMP alone or with PSA-TRICOM vaccine...
October 18, 2016: Oncotarget
H Choe, A Sboner, H Beltran, D Nanus, S T Tagawa
INTRODUCTION: Neuroendocrine prostate cancer (NEPC) is an aggressive late-stage variant of PC that is often androgen-receptor negative. Most clinicians believe the VTE rate with NEPC is higher than with standard metastatic castration-resistant PC (mCRPC), but NEPC tends to present with bulkier visceral disease and include platinum chemotherapy unlike standard PC. In many solid tumors, a more aggressive phenotype correlates with increased VTE risk and elevated expression of coagulation factors...
April 2016: Thrombosis Research
M Miederer, C Thomas, J Beck, C Hampel, C Krieger, P E Baqué, A Helisch, M Schreckenberger
UNLABELLED: In patients with metastasized, castration resistant prostate cancer (mCRPC) treatment with radium-223 (Xofigo) is an attractive therapeutic option. In particular, patients with high tumour load seem to profit from this treatment in regard of survival and quality of live. Aim of this study was to stratify mCRPC patients according to a quantitative imaging marker derived from routine bone scans (EXINI bone) and analyze haematopoietic toxicity of Xofigo in these patients. PATIENTS, METHODS: Toxicity and oncologic outcome were investigated in a cohort of 14 patients with high tumour load...
2015: Nuklearmedizin. Nuclear Medicine
Edwin E Reyes, David J VanderWeele, Masis Isikbay, Ryan Duggan, Alexa Campanile, Walter M Stadler, Donald J Vander Griend, Russell Z Szmulewitz
BACKGROUND: Many current therapies for metastatic castration-resistant prostate cancer (mCRPC) are aimed at AR signaling; however, resistance to these therapies is inevitable. To personalize CRPC therapy in an individual with clinical progression despite maximal AR signaling blockade, it is important to characterize the status of AR activity within their cancer. Biopsies of bone metastases are invasive and frequently fail to yield sufficient tissue for further study. Evaluation of circulating tumor cells (CTCs) offers an alternative, minimally invasive mechanism to characterize and study late-stage disease...
November 26, 2014: Journal of Translational Medicine
Phillip Parente, Francis Parnis, Howard Gurney
Prior to 2010, docetaxel was the standard option for chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). Today, the picture is vastly different: several additional therapies have each demonstrated a survival benefit such that we now have chemotherapy (cabazitaxel), androgen suppressive agents (abiraterone acetate and enzalutamide), a cellular vaccine (sipuleucel-T) and radium-233 (for symptomatic bone metastases). With several other agents in the pipeline for late-stage disease, the future looks promising for mCRPC...
September 2014: Asia-Pacific Journal of Clinical Oncology
Xiaosai Yao, Atish D Choudhury, Yvonne J Yamanaka, Viktor A Adalsteinsson, Todd M Gierahn, Christina A Williamson, Carla R Lamb, Mary-Ellen Taplin, Mari Nakabayashi, Matthew S Chabot, Tiantian Li, Gwo-Shu M Lee, Jesse S Boehm, Philip W Kantoff, William C Hahn, K Dane Wittrup, J Christopher Love
Ample evidence supports genetic and functional heterogeneity in primary tumors, but it remains unclear whether circulating tumor cells (CTCs) also exhibit the same hierarchical organization. We examined the functional diversity of viable, single CTCs using an array of subnanoliter wells (nanowells). The compartmentalization of single cells by nanowells allowed clonal comparison and mapping of heterogeneity of single cells or preformed clusters of cells. By measuring the short-term viability, invasiveness and secretory profiles of individual CTCs, it was evident that only a rare subset of CTCs possessed malignant traits indicative of metastatic potential in late-stage, progressing metastatic castration-resistant prostate cancer (mCRPC) patients...
April 2014: Integrative Biology: Quantitative Biosciences From Nano to Macro
Srikala S Sridhar, Stephen J Freedland, Martin E Gleave, Celestia Higano, Peter Mulders, Chris Parker, Oliver Sartor, Fred Saad
CONTEXT: Until recently, the only approved agent for metastatic castration-resistant prostate cancer (mCRPC) was docetaxel chemotherapy. But over the last 5 years, significant advances in the field have led to the approval of five new agents, each with different mechanisms of action and demonstrating improved overall survival in separate randomized phase 3 trials. Many of these novel agents are now also being evaluated in earlier stages of the disease, which may ultimately lead to even better outcomes...
February 2014: European Urology
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