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https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#1
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
May 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28482671/advances-in-evidence-based-cancer-adoptive-cell-therapy
#2
Chunlei Ge, Ruilei Li, Xin Song, Shukui Qin
Adoptive cell therapy (ACT) has been developed in cancer treatment by transferring/infusing immune cells into cancer patients, which are able to recognize, target, and destroy tumor cells. Recently, sipuleucel-T and genetically-modified T cells expressing chimeric antigen receptors (CAR) show a great potential to control metastatic castration-resistant prostate cancer and hematologic malignancies in clinic. This review summarized some of the major evidence-based ACT and the challenges to improve cell quality and reduce the side effects in the field...
April 2017: Chinese Clinical Oncology
https://www.readbyqxmd.com/read/28441112/second-line-hormonal-therapy-for-men-with-chemotherapy-na%C3%A3-ve-castration-resistant-prostate-cancer-american-society-of-clinical-oncology-provisional-clinical-opinion
#3
Katherine S Virgo, Ethan Basch, D Andrew Loblaw, Tom Oliver, R Bryan Rumble, Michael A Carducci, Luke Nordquist, Mary-Ellen Taplin, Eric Winquist, Eric A Singer
Purpose ASCO provisional clinical opinions (PCOs) offer direction to the ASCO membership after publication or presentation of potential practice-changing data. This PCO addresses second-line hormonal therapy for chemotherapy-naïve men with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptoms. Clinical Context The treatment goal for CRPC is palliation. Despite resistance to initial androgen deprivation therapy, most men respond to second-line hormonal therapies...
April 25, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28427519/a-comprehensive-review-of-immunotherapies-in-prostate-cancer
#4
REVIEW
Manuel Caitano Maia, Aaron R Hansen
Prostate cancer is the second most common malignant neoplasm in men worldwide and the fifth cause of cancer-related death. Although multiple new agents have been approved for metastatic castration resistant prostate cancer over the last decade, it is still an incurable disease. New strategies to improve cancer control are needed and agents targeting the immune system have shown encouraging results in many tumor types. Despite being attractive for immunotherapies due to the expression of various tumor associated antigens, the microenvironment in prostate cancer is relatively immunosuppressive and may be responsible for the failures of various agents targeting the immune system in this disease...
May 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28376158/role-of-antigen-spread-and-distinctive-characteristics-of-immunotherapy-in-cancer-treatment
#5
James L Gulley, Ravi A Madan, Russell Pachynski, Peter Mulders, Nadeem A Sheikh, James Trager, Charles G Drake
Immunotherapy is an important breakthrough in cancer. US Food and Drug Administration-approved immunotherapies for cancer treatment (including, but not limited to, sipuleucel-T, ipilimumab, nivolumab, pembrolizumab, and atezolizumab) substantially improve overall survival across multiple malignancies. One mechanism of action of these treatments is to induce an immune response against antigen-bearing tumor cells; the resultant cell death releases secondary (nontargeted) tumor antigens. Secondary antigens prime subsequent immune responses (antigen spread)...
April 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28361045/phase-i-clinical-trial-of-sipuleucel-t-combined-with-escalating-doses-of-ipilimumab-in-progressive-metastatic-castrate-resistant-prostate-cancer
#6
Mark Scholz, Sabrina Yep, Micah Chancey, Colleen Kelly, Ken Chau, Jeffrey Turner, Richard Lam, Charles G Drake
BACKGROUND: Sipuleucel-T (SIP-T), which functions by stimulating cancer-specific dendritic cells, prolongs survival in men with prostate cancer. Ipilimumab (IPI) achieved a borderline survival advantage in a large randomized trial. SIP-T and IPI are potentially synergistic. PATIENTS AND METHODS: Nine men with progressive metastatic castrate-resistant prostate cancer (mCRPC) were treated prospectively with SIP-T followed immediately by IPI with one of the following doses of IPI: 1 mg/kg at 1 week after SIP-T; 1 mg/kg at 1 and 4 weeks after SIP-T; or 1 mg/kg at 1, 4, and 7 weeks after SIP-T...
2017: ImmunoTargets and Therapy
https://www.readbyqxmd.com/read/28321817/adverse-events-in-cancer-immunotherapy
#7
Noha Abdel-Wahab, Anas Alshawa, Maria E Suarez-Almazor
Cancer immunotherapy has resulted in durable responses in patients with metastatic disease, unseen with traditional chemotherapy. Several therapies have been approved by the Food and Drug Administration for the treatment of various cancers, including: immune checkpoint inhibitors, cytokines - interleukin 2 (IL-2) and interferon alpha (IFN), and the cancer vaccine sipuleucel-T. These therapies upregulate the immune system to enhance antitumor responses. As a consequence, they can cause inflammatory and immune-related adverse events that can affect one or more organs, can be serious, and on occasion lifethreatening...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28241742/3d-diversity-dynamics-differential-testing-a-proposed-pipeline-for-analysis-of-next-generation-sequencing-t-cell-repertoire-data
#8
Li Zhang, Jason Cham, Alan Paciorek, James Trager, Nadeem Sheikh, Lawrence Fong
BACKGROUND: Cancer immunotherapy has demonstrated significant clinical activity in different cancers. T cells represent a crucial component of the adaptive immune system and are thought to mediate anti-tumoral immunity. Antigen-specific recognition by T cells is via the T cell receptor (TCR) which is unique for each T cell. Next generation sequencing (NGS) of the TCRs can be used as a platform to profile the T cell repertoire. Though there are a number of software tools available for processing repertoire data by mapping antigen receptor segments to sequencing reads and assembling the clonotypes, most of them are not designed to track and examine the dynamic nature of the TCR repertoire across multiple time points or between different biologic compartments (e...
February 27, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28125362/duration-of-treatment-in-prostate-cancer-patients-treated-with-abiraterone-acetate-or-enzalutamide
#9
Dominic Pilon, Ajay S Behl, Lorie A Ellis, Bruno Emond, Patrick Lefebvre, Nancy A Dawson
BACKGROUND: Abiraterone acetate (AA) and enzalutamide (ENZ) are oral therapies offering survival benefit to metastatic castration-resistant prostate cancer (mCRPC) patients. Despite the availability of multiple treatment options for mCRPC, there is a lack of information on the effect that being initiated on AA or ENZ has on the combined prostate cancer treatment duration. OBJECTIVE: To compare the combined duration of prostate cancer treatments of patients initiated on AA with that of patients initiated on ENZ...
February 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28113097/the-immune-infiltrate-in-prostate-bladder-and-testicular-tumors-an-old-friend-for-new-challenges
#10
REVIEW
Cinzia Solinas, Nieves Martinez Chanzá, Ahmad Awada, Mario Scartozzi
In genito-urinary tumors immunotherapy has been administered for a long time: Calmette-Guèrin Bacillus as adjuvant treatment in high risk patients with non muscle invasive urothelial bladder cancer and interleukin-2 and interferon-α in metastatic kidney cancer. The vaccine Sipuleucel-T has been approved by United States Food and Drug Administration for the treatment of castration resistant prostate cancer patients with asymptomatic or minimally symptomatic disease, given the 22% reduction of mortality risk in this group...
February 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28096932/contemporary-agents-in-the-management-of-metastatic-castration-resistant-prostate-cancer
#11
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/28063195/first-line-non-cytotoxic-therapy-in-chemotherapy-naive-patients-with-metastatic-castration-resistant-prostate-cancer-a-systematic-review-of-10-randomised-clinical-trials
#12
REVIEW
Michiel H F Poorthuis, Robin W M Vernooij, R Jeroen A van Moorselaar, Theo M de Reijke
The aim of this study is to systematically evaluate all available treatment options in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC). We systematically searched PubMed, EMBASE, and the Cochrane libraries up to 1 March 2016 for peer-reviewed publications on randomised clinical trials (RCTs). RCTs were included if progression-free survival (PFS), overall survival (OS), quality of life (QoL), or adverse events (AEs) were quantitatively evaluated. We assessed the risk of bias with the Cochrane Collaboration's tool and graded the evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group's approach...
June 2017: BJU International
https://www.readbyqxmd.com/read/28057178/immunoth%C3%A3-rapie-dans-les-cancers-de-la-prostate
#13
Stéphane Oudard, Constance Thibault, Antoine Angelergues, Eric Tartour, Marc Olivier Timsit, Arnaud Mejean, Constance Michel, Yann Vano
Immunotherapy is moving forward in prostate cancer. The autologous vaccine, Sipuleucel-T has been the first vaccine to be approved by FDA. First results with GVAX, tasquinimob or anti-PD-1 have been disappointing. Ipilimumab seen to be more active at an earlier stage of prostate disease. Identifying predictive factor or surrogate markers of activity of immunotherapy and which agents are clinically effective alone or in combination with others therapies such as hormonal or bone targeted therapies are warranted...
November 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/28025978/immune-targets-and-neoantigens-for-cancer-immunotherapy-and-precision-medicine
#14
REVIEW
Rong-Fu Wang, Helen Y Wang
Harnessing the immune system to eradicate malignant cells is becoming a most powerful new approach to cancer therapy. FDA approval of the immunotherapy-based drugs, sipuleucel-T (Provenge), ipilimumab (Yervoy, anti-CTLA-4), and more recently, the programmed cell death (PD)-1 antibody (pembrolizumab, Keytruda), for the treatment of multiple types of cancer has greatly advanced research and clinical studies in the field of cancer immunotherapy. Furthermore, recent clinical trials, using NY-ESO-1-specific T cell receptor (TCR) or CD19-chimeric antigen receptor (CAR), have shown promising clinical results for patients with metastatic cancer...
January 2017: Cell Research
https://www.readbyqxmd.com/read/27928429/what-is-the-role-of-sipuleucel-t-in-the-treatment-of-patients-with-advanced-prostate-cancer-an-update-on-the-evidence
#15
REVIEW
Rachel Hu, Daniel J George, Tian Zhang
Prostate cancer is the most common cancer in men and the second most deadly. About one-third of patients with prostate cancer will develop metastatic disease. We discuss the six United States Food and Drug Administration (FDA) approved treatments for metastatic castrate-resistant prostate cancer (mCRPC) with a strong focus on sipuleucel-T. Sipuleucel-T is the first immunotherapy shown to improve survival in asymptomatic or minimally-symptomatic mCRPC. Herein, we discuss the proposed mechanism of sipuleucel-T and its synthesis...
August 2016: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/27879971/tcr-diversity-a-universal-cancer-immunotherapy-biomarker
#16
EDITORIAL
Douglas G McNeel
Sipuleucel-T was approved as a treatment for men with advanced metastatic, castration-resistant prostate cancer on the basis of improved survival in randomized clinical trials. A major challenge for this therapy, as well as other newer cancer immunotherapy agents, has been to identify markers that can identify patients who benefit from these therapies. In a recent manuscript by Sheikh and colleagues, the investigators evaluated changes in T cell clonality in the peripheral blood and tumors of patients treated with sipuleucel-T using next generation sequencing of T cell receptor Vß CDR3 sequences...
2016: Journal for Immunotherapy of Cancer
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
#17
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/27843208/immunotherapy-in-metastatic-prostate-cancer
#18
REVIEW
Susan F Slovin
INTRODUCTION: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. METHODS: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. RESULTS: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer...
October 2016: Indian Journal of Urology: IJU: Journal of the Urological Society of India
https://www.readbyqxmd.com/read/27836866/sequencing-of-sipuleucel-t-and-androgen-deprivation-therapy-in-men-with-hormone-sensitive-biochemically-recurrent-prostate-cancer-a-phase-ii-randomized-trial
#19
Emmanuel S Antonarakis, Adam S Kibel, Evan Y Yu, Lawrence I Karsh, Aymen Elfiky, Neal D Shore, Nicholas J Vogelzang, John M Corman, Frederick E Millard, Johnathan C Maher, Nancy N Chang, Todd DeVries, Nadeem A Sheikh, Charles G Drake
Purpose: STAND, a randomized, phase II, open-label trial (NCT01431391), assessed sequencing of sipuleucel-T (an autologous cellular immunotherapy) with androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC) patients at high risk for metastasis.Experimental Design: Men with BRPC following prostatectomy and/or radiotherapy, a PSA doubling time ≤12 months, and no metastasis were enrolled. Patients were randomized (34/arm) to sipuleucel-T followed by ADT (started 2 weeks after sipuleucel-T completion), or ADT followed by sipuleucel-T (started 12 weeks after ADT initiation); ADT continued for 12 months in both arms...
November 10, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27822685/sequencing-treatment-for-castration-resistant-prostate-cancer
#20
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
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