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Darren M C Poon, Kuen Chan, Siu H Lee, Tim W Chan, Henry Sze, Eric K C Lee, Daisy Lam, Michelle F T Chan
Background: This study aimed to compare the efficacy of abiraterone acetate (AA) versus docetaxel (T) as first-line treatment in chemo-naïve metastatic castration-resistant prostate cancer (mCRPC) patients with or without the ineligible factors of the COU-AA-302 study (presence of visceral metastases, symptomatic disease, and/or Eastern Cooperative Oncology Group performance status ≥ 2). Materials and methods: The clinical records of chemo-naïve mCRPC patients who received AA in six public oncology centers or T in two of these centers between 2003 and 2014 were reviewed...
March 2018: Prostate International
Takashi Nagai, Taku Naiki, Keitaro Iida, Toshiki Etani, Ryosuke Ando, Shuzo Hamamoto, Yosuke Sugiyama, Hidetoshi Akita, Hiroki Kubota, Yoshihiro Hashimoto, Noriyasu Kawai, Takahiro Yasui
Background: Development of novel agents targeting the androgen axis has led to improved overall survival in castration-resistant prostate cancer (CRPC). This study aimed to investigate the optimal timing of treatment with one such agent, abiraterone acetate (AA), in Japanese patients. Materials and methods: Between July 2014 and February 2016, 106 CRPC patients were administered AA in Nagoya City University Hospital, Nagoya, Japan and in four affiliated hospitals following failure of primary combined androgen blockade (CAB)...
March 2018: Prostate International
Yue Zhao, Hao Huang, Changhao Chen, Hao Liu, Hongwei Liu, Feng Su, Junming Bi, Thomas B Lam, Jiaping Li, Tianxin Lin, Jian Huang
Background : Most patients receiving docetaxel-based chemotherapy for castration resistant prostate cancer (CRPC) will eventually progress, and the optimal interventions for these patients are controversial. The objective of our study is to evaluate the clinical efficacy and safety of pharmacological interventions for CRPC patients progressing after docetaxel-based chemotherapy. Methods : A systematic review and Bayesian network meta-analysis of the literature was carried out according to standard methods. Major electronic databases including PubMed, Web of Science and Embase were searched until Jan 2017...
2018: Journal of Cancer
Theodore Gourdin
PURPOSE OF REVIEW: Summarizes recent advances in the treatment of metastatic castration-sensitive and castration-resistant prostate cancer. RECENT FINDINGS: New randomized data suggest a survival advantage to early abiraterone in castration-sensitive metastatic prostate cancer. Prospective and retrospective studies are examining sequencing of existing cytotoxic and androgen-receptor-targeted therapies in both castration-sensitive and castration-resistant disease...
March 16, 2018: Current Opinion in Oncology
Masato Yasui, Yoriko Hasegawa, Takashi Kawahara, Yohei Kumano, Yasuhide Miyoshi, Nobuaki Matsubara, Hiroji Uemura
Abiraterone acetate (AA), a CYP17 inhibitor, now has a crucial role in the treatment of castration-resistant prostate cancer (CRPC), and previous studies have reported several prognostic clinical factors for AA treatment. The neutrophil-to-lymphocyte ratio (NLR) has also been investigated for a CRPC treatments in a few reports, however it has not been identified to be a prognostic factor for AA treatment in Japanese patients. The present study aimed to assess the association of the baseline NLR with the overall survival (OS) in CPRC patients treated by AA...
April 2018: Molecular and Clinical Oncology
Atul Bhatnagar, Matthew J McKay, Megan Crumbaker, Ketan Ahire, Peter Karuso, Howard Gurney, Mark P Molloy
Abiraterone acetate is administered as a prodrug to patients with metastatic, castration-resistant prostate cancer (mCRPC) and is readily metabolized into the potent 17a-hydroxylase/17,20-lyase (CYP17) enzyme inhibitor and androgen receptor inhibitor abiraterone and Δ(4)-abiraterone (D4A), respectively. To investigate pharmacokinetic variability in abiraterone acetate metabolism we developed highly sensitive liquid chromatography/mass spectrometry (LC/MS) assays for the simultaneous quantitation of abiraterone and D4A in human plasma using high-resolution mass spectrometry (HRMS) on an Orbitrap mass spectrometer...
March 6, 2018: Journal of Pharmaceutical and Biomedical Analysis
Matthew R Sydes, Melissa R Spears, Malcolm D Mason, Noel W Clarke, David P Dearnaley, Johann S de Bono, Gert Attard, Simon Chowdhury, Bill Cross, Silke Gillessen, Zaf Malik, Rob Jones, Chris Parker, Alastair W S Ritchie, J Martin Russell, Robin Millman, David Matheson, Claire Amos, Clare Gilson, Alison Birtle, Susannah Brock, Lisa Capaldi, Prabir Chakraborti, Ananya Choudhury, Linda Evans, Daniel Ford, Joanna Gale, Stephanie Gibbs, Duncan Gilbert, Robert Hughes, Duncan McLaren, Jason Lester, Ashok Nikapota, Joe O'Sullivan, Omi Parikh, Clive Peedell, Andrew Protheroe, Sarah M Rudman, Richard Shaffer, Denise Sheehan, Matthew Simms, Narayanan Srihari, Räto Strebel, Santhanam Sundar, Shaun Tolan, David Tsang, Mohini Varughese, John Wagstaff, Mahesh K B Parmar, Nicholas D James
Background: Adding abiraterone acetate with prednisolone (AAP) or docetaxel with prednisolone (DocP) to standard-of-care (SOC) each improved survival in STAMPEDE: a multi-arm multi-stage platform randomised controlled protocol recruiting patients with high-risk locally advanced or metastatic PCa starting long-term androgen deprivation therapy (ADT). The protocol provides the only direct, randomised comparative data of SOC+AAP vs SOC+DocP. Method: Recruitment to SOC+DocP and SOC+AAP overlapped Nov-2011─Mar-2013...
February 26, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Megan E V Caram, Jason P Estes, Jennifer J Griggs, Paul Lin, Bhramar Mukherjee
BACKGROUND: Several systemic treatments have been shown to increase survival for patients with metastatic castration-resistant prostate cancer. This study sought to characterize variation in use of the six "focus drugs" (docetaxel, abiraterone, enzalutamide, sipuleucel-T, radium-223, and cabazitaxel) that have been approved by the Food and Drug Administration for the treatment of metastatic castration-resistant prostate cancer during the years 2010-2015. We hypothesized that the use of these treatments would vary over time and by region of the country...
March 6, 2018: BMC Cancer
Takatsugu Okegawa, Naoki Ninomiya, Kazuki Masuda, Yu Nakamura, Mitsuhiro Tambo, Kikuo Nutahara
OBJECTIVE: We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide. METHODS: We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay...
March 5, 2018: Prostate
Laura Graham, Kalyan Banda, Alba Torres, Brett S Carver, Yu Chen, Katie Pisano, Greg Shelkey, Tracy Curley, Howard I Scher, Tamara L Lotan, Andrew C Hsieh, Dana E Rathkopf
Background MLN0128 is a first-in-class, dual mTOR inhibitor with potential to outperform standard rapalogs through inhibition of TORC1 and TORC2. This phase II study was designed to assess antitumor activity of MLN0128 in metastatic castration-resistant prostate cancer (mCRPC). Methods Eligible patients had mCRPC previously treated with abiraterone acetate and/or enzalutamide. Five patients started MLN0128 at 5 mg once daily, subsequently dose reduced to 4 mg because of toxicity. Four subsequent patients started MLN0128 at 4 mg daily...
March 6, 2018: Investigational New Drugs
Ellen Heitzer, Michael R Speicher
<b/> In this issue of Cancer Discovery , Miyamoto and colleagues adapted their microfluidic CTC-iChip isolation platform with a digital RNA-PCR readout for eight prostate-specific transcripts and two assays for the androgen receptor mRNA splice variant ARV7 and the TMPRSS2-ERG translocation transcript. In patients with metastatic castrate-resistant prostate cancer at initiating abiraterone therapy in a first-line setting, the resulting RNA-based digital circulating tumor cell signatures identified patients with a shorter overall survival, and in patients with clinically localized disease, the signatures identified those with seminal vesicle invasion and pelvic lymph node involvement...
March 2018: Cancer Discovery
Zineb Hamilou, Giulia Baciarello, Karim Fizazi
Both docetaxel+androgen deprivation therapy (ADT) and abiraterone acetate 1000mg/d+prednisone/prednisolone 5mg/d+ADT improved survival in patients with metastatic castration-naive prostate cancer. Their use should be offered and guided by patient's own characteristics.
February 27, 2018: European Urology Focus
Yusuke Ito, Marianne D Sadar
Enzalutamide is a nonsteroidal antiandrogen for the treatment of metastatic castration-resistant prostate cancer (mCRPC) both before and after chemotherapy. Enzalutamide is more effective than its predecessor bicalutamide, which was analyzed in head-to-head studies of patients with CRPC. This family of nonsteroidal antiandrogens is now comprised of four drugs approved by the US Food and Drug Administration with two investigational drugs in clinical trials. Antiandrogens have been employed clinically for more than five decades to provide a rich resource of information...
2018: Research and Reports in Urology
Anna Maria Mangano, Massimiliano Pacilio, Pasquale Ialongo, Alessandro Semprebene, Guido Ventroni, Lucio Mango
Here, we present the case of a 64-year-old male patient diagnosed with castration-resistant prostate cancer (CRPC) with bone metastasis, treated with abiraterone prednisone/prednisolone in combination with223 Ra-dichloride therapy, who had remission and a subsequent relapse of bone metastasis on repeated bone scans after therapy. We also discuss the possibility of continuing the223 Ra-dichloride therapy over the six planned administrations by administering other cycles at the same dose or at higher doses, if shown to be devoid of a significant increase in side effects, based on dosimetry considerations...
February 27, 2018: Diagnostics
Abhimanyu Thakur, Aishwarya Roy, Arijit Ghosh, Mohit Chhabra, Sugato Banerjee
No abstract text is available yet for this article.
February 26, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Jacob M Elkon, Ralph L Millett, Kristin F Millado, Jianqing Lin
Androgen deprivation therapy (ADT) has been the standard of care for the treatment of newly diagnosed metastatic prostate cancer for the past 70 years. Furthermore, adding docetaxel chemotherapy to ADT significantly improved patient survival, and thus became the new standard for patients with high volume disease. However, recent evidence has called this treatment strategy into question since a published study has shown that the drug abiraterone has a similar benefit to docetaxel in a similar patient population group but with less toxicity...
March 1, 2018: Expert Opinion on Pharmacotherapy
Loay Kassem, Kyrillus S Shohdy, Omar Abdel-Rahman
BACKGROUND: A major, yet precisely studied, shift has occurred in treatment of advanced hormone-sensitive prostate cancer (HSPC) by addition of docetaxel to androgen deprivation therapy (ADT) in the first-line. Recently, two landmark trials showed that abiraterone acetate (AA) can be an effective alternative along with ADT in the same setting. We implemented a network meta-analysis to compare safety and efficacy of both combinations. METHODS: PubMed database, ASCO and ESMO meeting library databases of all results published until June 2017 were searched using the keywords: "prostate cancer" AND "docetaxel" OR "abiraterone acetate"...
February 28, 2018: Current Medical Research and Opinion
Xiao X Wei, Adam P Siegel, Rahul Aggarwal, Amy M Lin, Terence W Friedlander, Lawrence Fong, Won Kim, Mirela Louttit, Emily Chang, Li Zhang, Charles J Ryan
LESSONS LEARNED: In abiraterone- and/or enzalutamide-refractory metastatic castration-resistant prostate cancer (mCRPC) patients, selinexor led to prostate-specific antigen and/or radiographic responses in a subset of patients, indicating clinical activity in this indication.Despite twice-a-week dosing and maximal symptomatic management, selinexor was associated with significant anorexia, nausea, and fatigue in mCRPC patients refractory to second-generation anti-androgen therapies, limiting further clinical development in this patient population...
February 27, 2018: Oncologist
Meftun Çulpan, Asıf Yıldırım, Turgay Turan, Turhan Çaşkurlu
Prostate cancer is the most common non-cutaneous malignancy and the second cause of cancer death in men. Despite improvements in diagnostic methods, the primary diagnosis of a number of patients may still be on metastatic stage. Cutaneous and supraclavicular lymph nodes are very rare metastatic sites for prostate cancer. In this report we present an extremely rare prostate cancer case diagnosed with supraclavicular lymph node and then developed cutaneous metastasis. A 64 year-old man was admitted to an internal medicine outpatient clinic with supraclavicular lymph node and biopsy of lymph node showed an adenocarcinoma...
January 2018: Turkish Journal of Urology
Kagenori Ito, Takahiro Kimura, Hajime Onuma, Ryuji Tabata, Tatsuya Shimomura, Kenta Miki, Masayuki Tomita, Shin Egawa
BACKGROUND: Guidelines define docetaxel as a first-line therapeutic option for metastatic castration-resistant prostate cancer (mCRPC). However, the role of docetaxel in non-metastatic castration-resistant prostate cancer (nmCRPC) has not been fully investigated. The aim of this retrospective study was to evaluate the potential role of docetaxel in nmCRPC. Clinical outcomes including overall survival were compared between CRPC patients who had docetaxel introduced while in nonmetastatic versus metastatic diseases...
February 23, 2018: Prostate
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