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enzalutamide side-effects

Changcheng Guo, Shuyuan Yeh, Yuanjie Niu, Gonghui Li, Junhua Zheng, Lei Li, Chawnshang Chang
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941...
March 18, 2017: Cancer Letters
C H Ohlmann, P Thelen
Androgen deprivation is still standard therapy for prostate cancer, either as primary androgen deprivation therapy or with the use of secondary hormonal drugs including abiraterone and enzalutamide. However, especially the clinically occult side effects like metabolic changes or cardiovascular complications and effects on the psyche of the patient are often not recognized in daily practice. Active monitoring of such side effects is essential for prevention and early intervention. In addition, the efficacy of androgen deprivation therapies is limited by primary and secondary resistance...
February 28, 2017: Der Urologe. Ausg. A
Sergey A Dyshlovoy, Katharina Otte, Winfried H Alsdorf, Jessica Hauschild, Tobias Lange, Simone Venz, Christiane K Bauer, Robert Bähring, Kerstin Amann, Ramin Mandanchi, Udo Schumacher, Jennifer Schröder-Schwarz, Tatyana N Makarieva, Alla G Guzii, Kseniya M Tabakmakher, Sergey N Fedorov, Larisa K Shubina, Igor E Kasheverov, Heimo Ehmke, Thomas Steuber, Valentin A Stonik, Carsten Bokemeyer, Friedemann Honecker, Gunhild von Amsberg
Development of drug resistance is an inevitable phenomenon in castration-resistant prostate cancer (CRPC) cells requiring novel therapeutic approaches. In this study, efficacy and toxicity of Rhizochalinin (Rhiz) - a novel sphingolipid-like marine compound - was evaluated in prostate cancer models, resistant to currently approved standard therapies. In vitro activity and mechanism of action of Rhiz were examined in the human prostate cancer cell lines PC-3, DU145, LNCaP, 22Rv1, and VCaP. Rhiz significantly reduced cell viability at low micromolar concentrations showing most pronounced effects in enzalutamide and abiraterone resistant AR-V7 positive cells...
October 25, 2016: Oncotarget
Yusuke Noguchi, Yugo Kawashima, Hiroko Kawara, Masatomo Kaneko, Hiroo Nakauchi, Yoko Tokuyama
Cabazitaxelis a taxane-type antineoplastic agent used for treating prostate cancer. Although typical side effects include neutropenia and fatigue, no studies have investigated eye disorders as a possible side effect, and the details are not clear. Herein, we report our experience of an undeniable case of optic neuropathy caused by cabazitaxel. A 78-year-old man had been diagnosed with prostate cancer (cT3aN1M1b, stage IV) 3 years previously, with a treatment history of bicalutamide, leuprorelin, flutamide, docetaxel, abiraterone, and enzalutamide...
June 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Jing Jia, Feng Li, Xiao-Shuang Tang, Shan Xu, Yang Gao, Qi Shi, Wenhuan Guo, Xinyang Wang, Dalin He, Peng Guo
LncRNA DANCR suppresses differentiation of epithelial cells, however, its function in prostate cancer development is still unknown. In the present study, we found the expression of DANCR increases in prostate cancer tissues and cells compared to normal prostate tissues and cells, moreover, DANCR promotes invasion and migration of prostate cancer cells in vitro and metastasis of tumor xenografts in nude mice. Mechanistically, we found that TIMP2/3, which are critical metastasis inhibitor of prostate cancer, were down-regulated by DANCR synergistically with EZH2 through epigenetically silencing their promoter by chromatin immunoprecipitation assay...
June 21, 2016: Oncotarget
(no author information available yet)
No abstract text is available yet for this article.
April 2016: Clinical Advances in Hematology & Oncology: H&O
Simeng Wen, Jing Tian, Yuanjie Niu, Lei Li, Shuyuan Yeh, Chawnshang Chang
Early studies suggested that prostate cancer (PCa) stem/progenitor (S/P) cells might play key roles to promote the tumor initiation and metastasis. Yet their linkage to the failure of androgen deprivation therapy (ADT), however, remains unclear. Here we demonstrated that the ADT with anti-androgens Casodex (also known as Bicalutamide) and Enzalutamide (also known as MDV3100), but not the newly identified AR degradation enhancer, ASC-J9(®), increased PCa S/P population, which might then lead to enhance the PCa cell invasion...
July 1, 2016: Cancer Letters
Masaki Shiota, Naohiro Fujimoto, Kenjiro Imada, Akira Yokomizo, Momoe Itsumi, Ario Takeuchi, Hidetoshi Kuruma, Junichi Inokuchi, Katsunori Tatsugami, Takeshi Uchiumi, Yoshinao Oda, Seiji Naito
BACKGROUND: Although androgen deprivation therapy for advanced prostate cancer initially exerts excellent anticancer effects, most prostate cancer treated with androgen deprivation therapy eventually recurs as castration-resistant prostate cancer (CRPC). Although aberrant kinase activation has been proposed as a mechanism of castration resistance, comprehensive kinase profiles in CRPC remain unknown. Therefore, we aimed to elucidate the kinome in CRPC as well as the role of key molecules...
July 2016: Journal of the National Cancer Institute
Tomoaki Hakariya, Hideki Sakai
Enzalutamide and abiraterone acetate are novel drugs for the treatment of castration resistant prostate cancer (CRPC). These agents clearly demonstrated improvements in PFS and OS in patients with CRPC in large randomized Phase III trials. However, the problems exist such as side effects, PSA flare, treatment biomarkers and sequence of the treatment. Further research is necessary to determine the optimal sequence of the treatment or the optimal combination approach with both enzalutamide and abiraterone acetate...
January 2016: Nihon Rinsho. Japanese Journal of Clinical Medicine
Jan Herden, Isabell Heidegger, Pia Paffenholz, Daniel Porres
The approval or clinical evaluation of several new agents - cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, and radium-223 - has significantly changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxel-based chemotherapy. All of these agents have resulted in a significant survival benefit as compared to their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and biological aggressiveness of the disease...
2015: Oncology Research and Treatment
Frank dela Rama, Caroline Pratz
BACKGROUND: Treatment of metastatic castration-resistant prostate cancer (mCRPC) has evolved rapidly. In particular, five new treatments that extend survival in mCRPC have been approved since 2010, including the chemotherapy cabazitaxel (Jevtana®), hormonal agents abiraterone (Zytiga®) and enzalutamide (Xtandi®), vaccine sipuleucel-T (Provenge®), and radiopharmaceutical radium-223 (Xofigo®); all have different indications and toxicity profiles. OBJECTIVES: This review discusses treatment advances in mCRPC, including considerations for side-effect management and treatment sequencing...
December 2015: Clinical Journal of Oncology Nursing
Harm Westdorp, G E Mette Benoist, Henk J Schers, P H Nielka van Erp, Winald R Gerritsen, Peter F A Mulders, C Kramers
Prostate cancer is the most common form of cancer in men in the Western world. One-third of the patients with localised prostate cancer will develop recurrent disease, localised disease spread or distant metastases. The presence of distant metastases is an indication for primary palliative hormone therapy. Intervention in the testosterone metabolism using hormone therapy is frequently accompanied by side effects and has a negative influence on the quality of life. Almost all prostate cancer patients show disease progression while on primary hormone therapy, despite having testosterone concentrations at castration level; they are then said to have castration-resistant prostate cancer (CRPC)...
2015: Nederlands Tijdschrift Voor Geneeskunde
Marie-Claire Desax, Thomas Hundsberger, Christian Rothermundt, Aurelius Omlin, Silke Gillessen
No abstract text is available yet for this article.
October 2015: Clinical Genitourinary Cancer
Qiang Dang, Lei Li, Hongjun Xie, Dalin He, Jiaqi Chen, Wenbing Song, Luke S Chang, Hong-Chiang Chang, Shuyuan Yeh, Chawnshang Chang
The recently developed anti-androgen enzalutamide also known as (MDV3100) has the advantage to prolong by 4.8 months the survival of castration resistant prostate cancer (CRPC) patients. However, the mechanisms behind the potential side effects involving the induction of the prostate cancer (PCa) neuroendocrine (NE) differentiation remain unclear. Here we found PCa cells could recruit more mast cells than normal prostate epithelial cells, and enzalutamide (or casodex) treatment could further increase such recruitment that resulted in promoting the PCa NE differentiation...
August 2015: Molecular Oncology
Celestia S Higano, Tomasz M Beer, Mary-Ellen Taplin, Eleni Efstathiou, Mohammad Hirmand, David Forer, Howard I Scher
BACKGROUND: Given that some patients with castration-resistant prostate cancer (CRPC) have shown extended responses to the androgen receptor inhibitor enzalutamide, long-term safety of this drug is of interest. OBJECTIVE: To evaluate the long-term safety and antitumor activity of enzalutamide in CRPC patients. DESIGN, SETTING, AND PARTICIPANTS: This phase 1-2 study evaluated enzalutamide in 140 CRPC patients with and without prior chemotherapy...
November 2015: European Urology
Julie N Graff, Max J Gordon, Tomasz M Beer
INTRODUCTION: Enzalutamide (MDV3100) is a second-generation androgen receptor antagonist that improves survival in metastatic, castration-resistant prostate cancer (mCRPC). Alternatives include chemotherapy, radiation, immunotherapy and abiraterone. AREAS COVERED: The Phase I/II study showed early evidence of efficacy and determined that fatigue is the dose-limiting toxicity. Two randomized, placebo-controlled trials have demonstrated superiority of enzalutamide 160 mg by mouth daily over placebo in terms of overall survival, radiographic progression-free survival as well as a broad range of secondary and exploratory end points in men who had received previous chemotherapy (AFFIRM) and in those who were chemotherapy naive (PREVAIL)...
April 2015: Expert Opinion on Pharmacotherapy
Nihar K Patel, Antoine Finianos, Kristen D Whitaker, Jeanny B Aragon-Ching
The advent of exponential growth of novel agents tested and approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) has brought about a need for understanding of the mechanism of action, side-effects, and clinical efficacy of these drugs as they relate to these patients. This review will provide a synopsis of the treatment landscape in mCRPC as varying agents such as abiraterone acetate, cabazitaxel, sipuleucel-T, radium, and selected emerging agents are presented...
2014: Therapeutics and Clinical Risk Management
Leonard G Gomella, Daniel P Petrylak, Bobby Shayegan
INTRODUCTION: Newer approaches to the management of advanced prostate cancer have rapidly evolved. While basic androgen deprivation remains as the first line in newly diagnosed hormone naïve metastatic prostate cancer, the agents used and strategies followed have undergone significant changes. Numerous new agents such as sipuleucel-T, abiraterone, enzalutamide, cabazitaxel and radium 223 have all been approved since 2010 to treat metastatic castration resistant prostate cancer (CRPC)...
April 2014: Canadian Journal of Urology
Athanasios Dellis, Athanasios G Papatsoris
Abiraterone acetate is an oral medication that has recently been granted approval for the treatment of metastatic castration resistant prostate cancer (mCRPC) prior and/or after chemotherapy with docetaxel. In this article we assess the economics of abiraterone acetate in mCRPC. Relevant studies demonstrated that abiraterone acetate had a minimal budget impact on health plans. A relevant advantage was the cost savings due to the lack of chemotherapy-related side effects as well as the ease of administration...
April 2014: Expert Review of Pharmacoeconomics & Outcomes Research
Rosa Nadal, Mary-Ellen Taplin, Joaquim Bellmunt
Enzalutamide is a second-generation androgen receptor signaling inhibitor that was approved by the US FDA in 2012 for the treatment of metastatic docetaxel-pretreated castrate-resistant prostate cancer. In preclinical studies, enzalutamide demonstrated higher affinity to the androgen receptor compared with the first-generation androgen receptor inhibitors. In the well-designed Phase III AFFIRM study, enzalutamide treatment showed improved overall survival compared with placebo in addition to improvement of all preplanned secondary parameters...
February 2014: Future Oncology
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