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https://www.readbyqxmd.com/read/28096932/contemporary-agents-in-the-management-of-metastatic-castration-resistant-prostate-cancer
#1
REVIEW
Anil Kapoor, Christopher Wu, Bobby Shayegan, Adrian P Rybak
Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28095710/the-evolving-role-of-chemotherapy-in-prostate-cancer
#2
Suliman Boulos, Danish Mazhar
Despite extensive clinical research of different chemotherapy agents for more than three decades, the role of chemotherapy in prostate cancer was only established in 2004, after demonstrating a survival benefit with docetaxel in metastatic castration-resistant prostate cancer. 6 years later, second-line chemotherapy using cabazitaxel, after disease progression on docetaxel, demonstrated an additional survival improvement. Recently, docetaxel given alongside standard hormonal therapy in newly diagnosed advanced prostate cancer was found to lead to significantly improved patient outcomes...
January 18, 2017: Future Oncology
https://www.readbyqxmd.com/read/28058445/safety-and-pharmacokinetics-of-cabazitaxel-in-patients-with-hepatic-impairment-a-phase-i-dose-escalation-study
#3
John Sarantopoulos, Alain C Mita, Aiwu He, James L Wade, Chung-Tsen Hsueh, John C Morris, A Craig Lockhart, David I Quinn, Jimmy Hwang, James Mier, Wenping Zhang, Claudine Wack, Jian Yin, Pierre-François Clot, Olivier Rixe
PURPOSE: Cabazitaxel has not been studied in patients with hepatic impairment (HI). This phase I study assessed cabazitaxel safety and pharmacokinetics in patients with HI. METHODS: Patients with advanced, non-hematologic cancer, and normal hepatic function (Cohort 1: C-1), or mild (C-2), moderate (C-3), severe (C-4) HI received cabazitaxel starting doses of 25, 20, 10, and 10 mg/m(2), respectively. Doses were escalated in patients with HI based on Cycle 1 dose-limiting toxicities (DLTs)...
January 5, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28039155/phase-i-ii-trial-of-cabazitaxel-plus-abiraterone-in-patients-with-metastatic-castration-resistant-prostate-cancer-mcrpc-progressing-after-docetaxel-and-abiraterone
#4
C Massard, J Mateo, Y Loriot, C Pezaro, L Albiges, N Mehra, A Varga, D Bianchini, C J Ryan, D P Petrylak, G Attard, L Shen, K Fizazi, J de Bono
BACKGROUND: Abiraterone and cabazitaxel improve survival in patients with metastatic castration-resistant prostate cancer (mCRPC). We conducted an open-label phase I/II trial of cabazitaxel plus abiraterone to assess the antitumor activity and tolerability in patients with progressive mCRPC after docetaxel (phase I), and after docetaxel and abiraterone (phase II) (NCT01511536). PATIENTS AND METHODS: The primary objectives were to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of cabazitaxel plus abiraterone (phase I), and the prostate-specific antigen (PSA) response defined as a ≥ 50% decrease confirmed ≥3 weeks later with this combination (phase II)...
October 18, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28038931/safety-of-same-day-pegfilgrastim-administration-in-metastatic-castration-resistant-prostate-cancer-treated-with-cabazitaxel-with-or-without-carboplatin
#5
Mehmet Asim Bilen, Diana H Cauley, Bradley J Atkinson, Hsiang-Chun Chen, Diana H Kaya, Xuemei Wang, Raghu Vikram, Shi-Ming Tu, Paul G Corn, Jeri Kim
INTRODUCTION: Although myeloid growth factors are commonly used to treat metastatic castration-resistant prostate cancer (mCRPC), the optimal timing of administration has not been well studied. We assessed the effects of same-day pegfilgrastim, a neutrophil stimulator, after cabazitaxel treatment with or without carboplatin in patients with mCRPC. We also evaluated the frequency of urinary tract inflammation during treatment. PATIENTS AND METHODS: Between September 2010 and September 2014, 151 consecutive patients with mCRPC underwent cabazitaxel treatment with or without the addition of carboplatin at a single institution...
December 13, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27960186/cabazitaxel-in-metastatic-castration-resistant-prostate-cancer-patients-progressing-after-docetaxel-a-prospective-single-center-study
#6
Giuseppe Cicero, Rossella De Luca, Patrizia Dorangricchia, Antonio Galvano, Giuseppe Lo Re, Vincenzo Serretta, Nino Dispensa, Francesco Dieli
PURPOSE: The present study aims to evaluate the efficacy of cabazitaxel in combination with prednisone treatment in Italian patients affected by hormone-refractory metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel plus prednisone. METHODS: Thirty patients with mCRPC were enrolled between June 2013 and January 2016 (the last follow-up was in January 2016). Cabazitaxel was used according to the summary of product characteristics and administered at a dose of 25 mg/m2 every 3 weeks plus oral prednisone at a dose of 5-mg tablets twice a day continuously...
December 14, 2016: Oncology
https://www.readbyqxmd.com/read/27903924/randomized-phase-ii-study-of-cabazitaxel-versus-methotrexate-in-patients-with-recurrent-and-or-metastatic-squamous-cell-carcinoma-of-the-head-and-neck-previously-treated-with-platinum-based-therapy
#7
Jean-Pascal Machiels, Aline Van Maanen, Jean-Marie Vandenbulcke, Bertrand Filleul, Emmanuel Seront, Stéphanie Henry, Lionel D'Hondt, Christophe Lonchay, Stéphane Holbrechts, Petra Boegner, Dany Brohee, Didier Dequanter, Ingrid Louviaux, Brieuc Sautois, Nicolas Whenham, Guy Berchem, Brigitte Vanderschueren, Christel Fontaine, Sandra Schmitz, Aline Gillain, Joelle Schoonjans, Sylvie Rottey
LESSONS LEARNED: Cabazitaxel has activity in squamous cell carcinoma of the head and neck (SCCHN) and taxane-resistant cell lines. For the first time, cabazitaxel was investigated in incurable patients with recurrent SCCHN. Patients were randomly assigned to cabazitaxel every 3 weeks or weekly methotrexate.This phase II study did not meet its primary endpoint.Cabazitaxel has low activity in SCCHN.The toxicity profile in this population also was not favorable owing to the high rate of febrile neutropenia observed (17%)...
December 2016: Oncologist
https://www.readbyqxmd.com/read/27890446/efficacy-of-therapies-after-galeterone-in-patients-with-castration-resistant-prostate-cancer
#8
Rana R McKay, Lillian Werner, Matthew Fiorillo, Jennifer Roberts, Elisabeth I Heath, Glenn J Bubley, Robert Bruce Montgomery, Mary-Ellen Taplin
BACKGROUND: Galeterone is a multi-targeted agent with activity as a CYP17 inhibitor, androgen receptor antagonist, and also causes androgen receptor degradation. It has shown meaningful anti-tumor activity with a well-tolerated safety profile in patients with castration-resistant prostate cancer (CRPC) in phase I and II studies; however, the efficacy of currently approved CRPC therapies after treatment with galeterone is unknown. In this study, we evaluate prostate specific antigen (PSA) response of non-protocol therapies following galeterone in a subset of patients treated on the Androgen Receptor Modulation Optimized for Response (ARMOR) 2 study...
October 27, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27885457/-psma-targeted-radioligand-therapy-in-prostate-cancer
#9
M M Heck, M Retz, R Tauber, K Knorr, C Kratochwil, M Eiber
Radioligand therapy (RLT) directed against prostate-specific membrane antigen (PSMA) enables tumor-specific treatment directed against PSMA-overexpressing prostate cancer cells. Several PSMA ligands such as PSMA-617 or PSMA-I&T have been developed that can be labeled with β‑radiating lutetium-177. These are currently applied in compassionate use programs to treat metastatic castration-resistant prostate cancer (mCRPC). PSMA-directed RLT is currently being offered in several nuclear medicine departments throughout Germany...
January 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27878318/-corticosteroids-in-the-management-of-advanced-prostate-cancer
#10
H Kübler
Corticosteroids have been widely used for decades in cancer therapy, predominantly due to their anti-inflammatory activity. In the treatment of metastatic castration-resistant prostate cancer (mCRPC), corticosteroids play an important role both in the management of tumor-related symptoms, especially bone metastasis-related pain, and as concomitant treatment to counteract side effects associated with approved active prostatic anticancer agents such as docetaxel, cabazitaxel, and abiraterone acetate. In association with abiraterone acetate, low-dose corticosteroids (prednisone or prednisolone) reduce the mineralocorticoid side effects of abiraterone...
November 22, 2016: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/27876504/disease-and-treatment-characteristics-of-men-diagnosed-with-metastatic-hormone-sensitive-prostate-cancer-in-real-life-analysis-from-a-commercial-claims-database
#11
Thomas W Flaig, Ravi C Potluri, Yvette Ng, Mary B Todd, Maneesha Mehra, Celestia S Higano
BACKGROUND: Our understanding of the clinical characteristics and treatment patterns of men who present with newly diagnosed metastatic (M1) hormone-sensitive prostate cancer is based mainly on clinical trial data. We sought to characterize the M1 population seen in routine clinical practice using a commercial claims database. PATIENTS AND METHODS: A US claims (2000-2013) database was used to identify patients with an index diagnosis of prostate cancer. M1 patients were identified by "International Classification of Diseases, 9th revision, Clinical Modification" diagnosis codes of metastasis to bone, viscera, distant lymph node, and unspecified sites within 90 days of the prostate cancer diagnosis...
October 18, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27875950/targeted-delivery-of-cabazitaxel-by-conjugation-to-albumin-peg-folate-nanoparticles-using-a-cysteine-acrylate-linker-and-simple-synthesis-conditions
#12
Mohammad Kazem Khoeeniha, Mehdi Esfandyari-Manesh, Hossein Behrouz, Mohsen Amini, Behrang Shiri Varnamkhasti, Fatemeh Atyabi, Rassoul Dinarvand
Cabazitaxel (CBZ) is a new taxane approved by the FDA for treatment of castration-resistant prostate cancer not responding to docetaxel. However, CBZ is not a suitable substrate for p-glycoprotein 60, an efflux pump which transports anticancer drugs out of malignant cells and is therefore a promising drug for treatment of multidrug resistant tumors. Similar to other taxanes, the presence of Tween 80 in the CBZ formulation shows that it is insoluble in water. Therefore, to increase the solubility and circulation time, a CBZ-albumin conjugate was synthesized...
November 22, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27873118/current-update-of-a-carboxymethylcellulose-peg-conjugate-platform-for-delivery-of-insoluble-cytotoxic-agents-to-tumors
#13
Yang Yang, Joseph Bteich, Shyh-Dar Li
Cytotoxic chemotherapeutic agents are used as the standard therapy for a range of significant cancers, but many of these drugs suffer from poor water solubility and low selectivity, limiting their clinical efficacy. To overcome these shortcomings, Cellax™ drug delivery platform was developed. Cellax™ is a polymer-based nanoparticle drug delivery system designed to solubilize hydrophobic drugs and target them to solid tumors, thereby enhancing the efficacy and reducing the side effects. Cellax-docetaxel (Cellax-DTX) displayed improved pharmacokinetic, safety, and efficacy profiles compared to native DTX (Taxotere®) and Nab-paclitaxel (Nab-PTX, Abraxane®) in multiple animal models...
November 21, 2016: AAPS Journal
https://www.readbyqxmd.com/read/27862097/phase-ib-trial-of-cabazitaxel-and-tasquinimod-in-men-with-heavily-pretreated-metastatic-castration-resistant-prostate-cancer-mcrpc-the-catch-trial
#14
Andrew J Armstrong, Michael S Humeniuk, Patrick Healy, Russell Szmulewitz, Carolyn Winters, Julie Kephart, Michael R Harrison, Elia Martinez, Kelly Mundy, Susan Halabi, Daniel George
BACKGROUND: Tasquinimod is an immunomodulating and anti-antiangiogenic oral agent with anti-prostate cancer activity in preclinical studies and in clinical trials of men with metastatic castration resistant prostate cancer (mCRPC), including single agent activity and in combination with taxanes. We sought to identify the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of tasquinimod in combination with cabazitaxel and prednisone in men with chemorefractory mCRPC. METHODS: Men with mCRPC who had failed prior docetaxel chemotherapy received cabazitaxel 25 mg/m(2) every 3 weeks with oral tasquinimod at 1 of 3 escalating dose levels (0...
November 16, 2016: Prostate
https://www.readbyqxmd.com/read/27843207/chemotherapy-options-in-castration-resistant-prostate-cancer
#15
REVIEW
Benjamin A Teply, Ralph J Hauke
INTRODUCTION: The treatment landscape for patients with metastatic castration-resistant prostate cancer (CRPC) is evolving, with recent approvals of immune therapy, novel hormonal therapy, and bone-targeted therapy. Chemotherapy remains an essential component of the armamentarium. Herein, we review current chemotherapy options for patients with CRPC and discuss future challenges. METHODS: We reviewed literature for chemotherapy agents in prostate cancer, with special attention to the evidence for efficacy of the currently approved agents...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/27822685/sequencing-treatment-for-castration-resistant-prostate-cancer
#16
REVIEW
Catherine E Handy, Emmanuel S Antonarakis
Prostate cancer is the most common non-cutaneous cancer diagnosed in men and the second leading cause of male cancer deaths in the USA. While most cases are diagnosed in early stages, some will present as or progress to metastatic disease and eventually castration-resistant prostate cancer (mCRPC) which has a mortality rate exceeding 50 %. There are currently six approved systemic life-prolonging therapies for use in mCRPC, yet little data to guide sequencing. Clinical factors, including the presence or absence of symptoms and the presence or absence of visceral metastases, should help determine the best therapeutic choice at each treatment node...
December 2016: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/27796539/a-phase-i-pharmacokinetic-and-safety-study-of-cabazitaxel-in-adult-cancer-patients-with-normal-and-impaired-renal-function
#17
Analía Azaro, Jordi Rodón, Jean-Pascal Machiels, Sylvie Rottey, Silvia Damian, Richard Baird, Javier Garcia-Corbacho, Ron H J Mathijssen, Pierre-François Clot, Claudine Wack, Liji Shen, Maja J A de Jonge
PURPOSE: Limited data are available on cabazitaxel pharmacokinetics in patients with renal impairment. This open-label, multicenter study assessed cabazitaxel in patients with advanced solid tumors and normal or impaired renal function. METHODS: Cohorts A (normal renal function: creatinine clearance [CrCL] >80 mL/min/1.73 m(2)), B (moderate renal impairment: CrCL 30 to <50 mL/min/1.73 m(2)) and C (severe impairment: CrCL <30 mL/min/1.73 m(2)) received cabazitaxel 25 mg/m(2) (A, B) or 20 mg/m(2) (C, could be escalated to 25 mg/m(2)), once every 3 weeks...
December 2016: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/27783994/combination-effect-of-therapies-targeting-the-pi3k-and-ar-signaling-pathways-in-prostate-cancer
#18
Shalini Singh Yadav, Jinyi Li, Jennifer A Stockert, James O'Connor, Bryan Herzog, Cordelia Elaiho, Matthew D Galsky, Ashutosh Kumar Tewari, Kamlesh Kumar Yadav
Several promising targeted-therapeutics for prostate cancer (PCa), primarily affecting the androgen receptor (AR) and the PI3K/AKT/mTOR-pathway, are in various phases of development. However, despite promise, single-agent inhibitors targeting the two pathways have not shown long-term benefits, perhaps due to a complex compensatory cross talk that exists between the two pathways. Combination therapy has thus been proposed to maximize benefit. We have carried out a systematic study of two-drug combination effect of MDV3100 (AR antagonist), BKM120 (PI3K inhibitor), TKI258 (pan RTK inhibitor) and RAD001 (mTOR inhibitor) using various PCa cell lines...
October 20, 2016: Oncotarget
https://www.readbyqxmd.com/read/27773999/role-of-chemotherapy-and-mechanisms-of-resistance-to-chemotherapy-in-metastatic-castration-resistant-prostate-cancer
#19
REVIEW
Vipin Lohiya, Jeanny B Aragon-Ching, Guru Sonpavde
Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide...
2016: Clinical Medicine Insights. Oncology
https://www.readbyqxmd.com/read/27770303/cabazitaxel-for-hormone-relapsed-metastatic-prostate-cancer-previously-treated-with-a-docetaxel-containing-regimen-an-evidence-review-group-perspective-of-a-nice-single-technology-appraisal
#20
Benjamin Kearns, Abdullah Pandor, Matt Stevenson, Jean Hamilton, Duncan Chambers, Mark Clowes, John Graham, M Satish Kumar
As part of its single technology appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures cabazitaxel (Jevtana(®), Sanofi, UK) to submit evidence for the clinical and cost effectiveness of cabazitaxel for treatment of patients with metastatic hormone-relapsed prostate cancer (mHRPC) previously treated with a docetaxel-containing regimen. The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG)...
October 22, 2016: PharmacoEconomics
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