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abiraterone cross resistance with docetaxel

Hideaki Miyake, Takuto Hara, Keita Tamura, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Masato Fujisawa
BACKGROUND: The objective of this study was to compare the efficacies of sequential therapies with novel androgen receptor-axis-targeted (ARAT) agents in patients with docetaxel-naïve metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This study included 108 consecutive patients with mCRPC who sequentially received abiraterone acetate (AA) and enzalutamide (Enz), in either order, without prior treatment with docetaxel. The combined prostate-specific antigen (PSA) progression-free survival (PFS) was defined as the sum of PFS1 and PFS2, representing PSA PFSs on the first and second ARAT agents, respectively...
December 22, 2016: Clinical Genitourinary Cancer
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
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
K Miller, P Albers, R Eichenauer, G Geiges, M-O Grimm, F König, G Mickisch, D Pfister, C Schwentner, H Suttmann, S Zastrow
Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient...
September 2016: Der Urologe. Ausg. A
Edoardo Francini, Christopher J Sweeney
UNLABELLED: For >6 yr, docetaxel with prednisone was the only treatment with survival benefits for metastatic castration-resistant prostate cancer (mCRPC). More recently, in clinical practice, abiraterone acetate has been commonly administered prior to docetaxel for the treatment of mCRPC. Our study aimed to review the activity of docetaxel after prior abiraterone. To this end, we analyzed all retrospective reports in the literature describing the overall survival (OS) of mCRPC patients treated with docetaxel after previous abiraterone...
September 2016: European Urology
S Hager, C J Ackermann, M Joerger, S Gillessen, A Omlin
BACKGROUND: For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents...
June 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Francesca Vignani, Valentina Bertaglia, Consuelo Buttigliero, Marcello Tucci, Giorgio V Scagliotti, Massimo Di Maio
Incidence of bone metastases is very high in advanced prostate cancer patients. Bone metastases likely have a significant impact on functional status and quality of life, not only related to pain, but also to the relevant risk of skeletal-related events. A better understanding of mechanisms associated with bone metastatic disease secondary to prostate cancer and more specifically to the cross-talk between tumor cells and bone microenvironment in metastatic progression represented the background for the development of new effective bone-targeted therapies...
March 2016: Cancer Treatment Reviews
P Thelen, J Gschwend, J-M Wolff, K Miller
With the development of Abiraterone and Enzalutamide new treatment option have become available in addition to Docetaxel for first-line treatment of castration resistant prostate cancer. However, resistance and ultimately failure occurs inevitably with all available treatment options. Moreover, cross-resistance leads to considerably reduced efficacy in second-line treatment. Preclinical data suggest discriminative mechanisms of resistance development for Abiraterone and Enzalutamide. Clinical confirmation of these putative mechanisms for treatment failure might facilitate recommendations for future sequencing of these drugs...
February 2016: Aktuelle Urologie
Sushil K Badrising, Vincent van der Noort, Alfons J M van den Eertwegh, Paul Hamberg, Inge M van Oort, Hendrik P van den Berg, Maartje Los, Maureen J B Aarts, Jules L L M Coenen, Hans Gelderblom, Igle J de Jong, Emile D Kerver, Suzan Vrijaldenhoven, Theo van Voorthuizen, Fabienne Warmerdam, John B Haanen, Andries M Bergman
BACKGROUND: Abiraterone Acetate (AA) and Enzalutamide (Enz) are effective hormonal treatments in mCRPC patients. Retrospective studies suggested clinical cross-resistance between Enz and AA. However, 12.8-39.1% of patients previously treated with docetaxel (Doc) and AA do respond to Enz. These responders have not been characterized. METHODS: 102 Enz treated mCRPC patients after AA and Doc treatment were included in this study. Differences in patient characteristics and previous treatment outcomes between PSA responders and non-responders on Enz were evaluated...
January 2016: Prostate
R J van Soest, A J M Nieuweboer, E S de Morrée, D Chitu, A M Bergman, S H Goey, M M Bos, N van der Meer, P Hamberg, R de Wit, R H J Mathijssen
INTRODUCTION: The treatment armamentarium for metastatic castration-resistant prostate cancer (mCRPC) has expanded with the introduction of several new therapies. In this treatment continuum, it is unclear whether the efficacy of cabazitaxel is affected by prior novel androgen receptor targeted therapies (ART) such as abiraterone and enzalutamide. In this study, we investigated the influence of prior ART on the efficacy of cabazitaxel in men with mCRPC. PATIENTS AND METHODS: Data from an ongoing multicentre, phase II trial were used comprising 114 men with mCRPC treated with cabazitaxel in the post-docetaxel setting...
November 2015: European Journal of Cancer
Sarah K Martin, Natasha Kyprianou
Prostate cancer is a tumor addicted to androgen receptor (AR) signaling, even in its castration resistant state, and recently developed antiandrogen therapies including Abiraterone acetate and enzalutamide effectively target the androgen signaling axis, but there is ultimately recurrence to lethal disease. Development of advanced castration-resistant prostate cancer (CRPC) is a biological consequence of lack of an apoptotic response of prostate tumor cells to androgen ablation. Taxanes represent the major clinically relevant chemotherapy for the treatment of patients with metastatic CRPC; unfortunately, they do not deliver a cure but an extension of overall survival...
2015: Advances in Cancer Research
Tian Zhang, Mallika S Dhawan, Patrick Healy, Daniel J George, Michael R Harrison, Jorge Oldan, Bennett Chin, Andrew J Armstrong
BACKGROUND: Abiraterone acetate (AA) has demonstrated improved outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). However, data are lacking on the effect of AA on subsequent efficacy of enzalutamide or docetaxel. PATIENTS AND METHODS: We included men with mCRPC who received AA and subsequent enzalutamide or docetaxel by August 12, 2013. Patients were separated into 3 groups: group A, treated with AA then enzalutamide before chemotherapy; group B, treated with AA then docetaxel; and group C, treated with AA and enzalutamide after chemotherapy...
August 2015: Clinical Genitourinary Cancer
Tian Zhang, Jason Zhu, Daniel J George, Andrew J Armstrong
INTRODUCTION: Over the past decade, treatment options for men with metastatic castration-resistant prostate cancer (CRPC) have expanded with the addition of abiraterone acetate (AA), enzalutamide, sipuleucel-T, radium-223, docetaxel and cabazitaxel. The optimal sequencing of therapies in the context of efficacy and known cross-resistance remains uncertain. AREAS COVERED: We review the development of enzalutamide (MDV3100, Xtandi), a novel second-generation androgen receptor (AR), and AA (Zytiga), a selective, irreversible inhibitor of cytochrome P17...
March 2015: Expert Opinion on Pharmacotherapy
Robert J van Soest, Ellen S de Morrée, Charlotte F Kweldam, Corrina M A de Ridder, Erik A C Wiemer, Ron H J Mathijssen, Ronald de Wit, Wytske M van Weerden
UNLABELLED: Treatment options for metastatic castration-resistant prostate cancer (CRPC) have evolved with the established benefit of the novel androgen receptor (AR)-targeted agents abiraterone and enzalutamide in the prechemotherapy setting. However, concerns regarding cross-resistance between the taxanes docetaxel and cabazitaxel and these AR-targeted agents have arisen, and the optimal drug treatment sequence is unknown. We investigated the in vivo efficacy of docetaxel and cabazitaxel in enzalutamide-resistant CRPC, and mechanisms of cross-resistance between these agents...
June 2015: European Urology
Kim Stuyckens, Fred Saad, Xu Steven Xu, Charles J Ryan, Matthew R Smith, Thomas W Griffin, Margaret K Yu, An Vermeulen, Partha Nandy, Italo Poggesi
BACKGROUND AND OBJECTIVES: Abiraterone acetate, an androgen biosynthesis inhibitor, prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) in the pre- and post-chemotherapy setting as demonstrated by the pivotal phase III studies COU-AA-301 and COU-AA-302. We performed population pharmacokinetic analyses to estimate pharmacokinetic parameters after oral administration of 1,000 mg/day of abiraterone acetate in patients with mCRPC, with or without prior chemotherapy, and after a single 1,000 mg dose in healthy volunteers...
December 2014: Clinical Pharmacokinetics
Rosa Nadal, Zhe Zhang, Hibba Rahman, Michael T Schweizer, Samuel R Denmeade, Channing J Paller, Michael A Carducci, Mario A Eisenberger, Emmanuel S Antonarakis
BACKGROUND: Two randomized clinical trials have demonstrated a survival advantage with enzalutamide over placebo in both docetaxel (D)-pretreated and D-naïve metastatic castration-resistant prostate cancer (mCRPC) patients. Cross-resistance between androgen receptor-directed therapies and taxanes has been suggested, possibly leading to lower efficacy of enzalutamide in the post-D setting. METHODS: We aimed to examine the impact of prior D treatment on the clinical activity of enzalutamide in patients with mCRPC...
November 2014: Prostate
Arun A Azad, Raya Leibowitz-Amit, Bernhard J Eigl, Renee Lester, J Connor Wells, R Nevin Murray, Christian Kollmannsberger, Daniel Y C Heng, Anthony M Joshua, Kim N Chi
BACKGROUND: Questions about optimal sequencing of systemic therapy in metastatic castration-resistant prostate cancer (mCRPC) and whether cross-resistance occurs between different drugs remain largely unanswered. Previous studies have produced conflicting data on the activity of docetaxel in patients who did not attain a prostate-specific antigen (PSA) response to abiraterone acetate (abiraterone). We investigated whether the biochemical response to abiraterone is associated with efficacy of subsequent docetaxel therapy...
November 2014: Prostate
Edoardo Francini, Roberto Petrioli, Giandomenico Roviello
Prostate cancer is the second leading cause of cancer-related deaths in men in most western countries. New agents for metastatic castration-resistant prostate cancer (CRPC) developed in the past 3 years include abiraterone acetate (AA) and enzalutamide (ENZ), which inhibit signaling by and synthesis of androgens, respectively. Because they share the same target, potential clinical cross-resistance between AA and E is possible. In this review, we discuss the results of clinical studies in which CRPC patients were treated with AA and E either separately or in sequence after first-line treatment with docetaxel...
October 2014: Expert Review of Anticancer Therapy
Cora N Sternberg, Daniel P Petrylak, Ravi A Madan, Chris Parker
The androgen receptor (AR) is the most significant target for patients with metastatic castration-resistant prostate cancer (mCRPC). There is now irrefutable evidence that the AR axis is functional in most patients throughout the history of prostate cancer, is crucial from diagnosis to death, even in patients who have received hormonal manipulation, and represents a relevant therapeutic target in all phases of the disease. The potential mechanisms of tumor escape after castration are multifold, with each mechanism today representing a therapeutic opportunity...
2014: American Society of Clinical Oncology Educational Book
Nader Al Nakouzi, Sylvestre Le Moulec, Laurence Albigès, Chris Wang, Philippe Beuzeboc, Marine Gross-Goupil, Thibault de La Motte Rouge, Aline Guillot, Dorota Gajda, Christophe Massard, Martin Gleave, Karim Fizazi, Yohann Loriot
BACKGROUND: Cabazitaxel, abiraterone acetate (AA), and enzalutamide have been approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel chemotherapy. Whether taxanes and next-generation androgen receptor (AR) axis inhibitors are cross-resistant or not is a subject of debate. OBJECTIVE: To evaluate the antitumour activity of cabazitaxel in mCRPC pretreated with abiraterone or enzalutamide. DESIGN, SETTING, AND PARTICIPANTS: The antitumour activity of cabazitaxel was assessed in patients with mCRPC and progressive disease after treatment with docetaxel and AA...
August 2015: European Urology
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