|
1
|
Chang O, Cheon S, Semenova N, Azad N, Iyer AK, Yakisich JS. Prolonged Low-Dose Administration of FDA-Approved Drugs for Non-Cancer Conditions: A Review of Potential Targets in Cancer Cells. Int J Mol Sci 2025; 26:2720. [PMID: 40141362 PMCID: PMC11942989 DOI: 10.3390/ijms26062720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2025] [Revised: 03/09/2025] [Accepted: 03/11/2025] [Indexed: 03/28/2025] Open
Abstract
Though not specifically designed for cancer therapy, several FDA-approved drugs such as metformin, aspirin, and simvastatin have an effect in lowering the incidence of cancer. However, there is a great discrepancy between in vitro concentrations needed to eliminate cancer cells and the plasma concentration normally tolerated within the body. At present, there is no universal explanation for this discrepancy and several mechanisms have been proposed including targeting cancer stem cells (CSCs) or cellular senescence. CSCs are cells with the ability of self-renewal and differentiation known to be resistant to chemotherapy. Senescence is a response to damage and stress, characterized by permanent cell-cycle arrest and apoptotic resistance. Although, for both situations, there are few examples where low concentrations of the FDA-approved drugs were the most effective, there is no satisfactory data to support that either CSCs or cellular senescence are the target of these drugs. In this review, we concisely summarize the most used FDA-approved drugs for non-cancer conditions as well as their potential mechanisms of action in lowering cancer incidence. In addition, we propose that prolonged low-dose administration (PLDA) of specific FDA-approved drugs can be useful for effectively preventing metastasis formation in selected patients.
Collapse
Affiliation(s)
- Olivia Chang
- Governor’s School for Science and Technology, Hampton, VA 23666, USA; (O.C.); (S.C.)
| | - Sarah Cheon
- Governor’s School for Science and Technology, Hampton, VA 23666, USA; (O.C.); (S.C.)
| | - Nina Semenova
- Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668, USA; (N.S.); (A.K.I.)
| | - Neelam Azad
- The Office of the Vice President for Research, Hampton University, Hampton, VA 23668, USA;
| | - Anand Krishnan Iyer
- Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668, USA; (N.S.); (A.K.I.)
| | - Juan Sebastian Yakisich
- Department of Pharmaceutical Sciences, School of Pharmacy, Hampton University, Hampton, VA 23668, USA; (N.S.); (A.K.I.)
| |
Collapse
|
|
2
|
Patel S, Saxena B, Mehta P, Niazi SK. GnRH Peptide Antagonist: Comparative Analysis of Chemistry and Formulation with Implications for Clinical Safety and Efficacy. Pharmaceuticals (Basel) 2024; 18:36. [PMID: 39861098 PMCID: PMC11768417 DOI: 10.3390/ph18010036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 12/25/2024] [Accepted: 12/29/2024] [Indexed: 01/27/2025] Open
Abstract
Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems. These characteristics qualify GnRH antagonists as revolutionary therapy for diseases such as advanced prostate cancer, endometriosis, uterine fibroids, and in vitro fertilization procedures. Key GnRH peptide antagonists authorized by the regulatory agencies include Cetrorelix, Ganirelix, Abarelix, Degarelix, and Teverelix. Assisted reproductive technologies (ART) are dominated by Cetrorelix and Ganirelix, while Degarelix and Abarelix have shown significant promise in treating advanced prostate cancer. Teverelix appears as a next-generation GnRH antagonist with an ideal mix of efficacy and safety, showing promise in a variety of reproductive and hormone-dependent illnesses. This review investigates the pharmacological role of GnRH in reproductive physiology and its consequences in disease, emphasizing structural advances in third- and fourth-generation GnRH antagonists. All GnRH peptide-based antagonists were analyzed in detail for formulation strategy, pharmacokinetics, effectiveness, and safety. This review also emphasizes GnRH antagonists' clinical promise, providing insights into their evolution and the possibility for future research in developing safer, more effective treatments for complicated hormonal diseases.
Collapse
Affiliation(s)
- Shikha Patel
- Department of Pharmaceutical Analysis, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India; (S.P.); (P.M.)
| | - Bhagawati Saxena
- Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India;
| | - Priti Mehta
- Department of Pharmaceutical Analysis, Institute of Pharmacy, Nirma University, Ahmedabad 382481, India; (S.P.); (P.M.)
| | | |
Collapse
|
|
3
|
Reiss AB, Vasalani S, Albert J, Drewes W, Li K, Srivastava A, De Leon J, Katz AE. The Effect of Androgen Deprivation Therapy on the Cardiovascular System in Advanced Prostate Cancer. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1727. [PMID: 39596912 PMCID: PMC11596556 DOI: 10.3390/medicina60111727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 10/09/2024] [Accepted: 10/17/2024] [Indexed: 11/29/2024]
Abstract
Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study.
Collapse
Affiliation(s)
- Allison B. Reiss
- Department of Medicine and Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (S.V.); (J.A.); (W.D.); (A.S.); (J.D.L.)
| | - Samantha Vasalani
- Department of Medicine and Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (S.V.); (J.A.); (W.D.); (A.S.); (J.D.L.)
| | - Jacqueline Albert
- Department of Medicine and Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (S.V.); (J.A.); (W.D.); (A.S.); (J.D.L.)
| | - Wendy Drewes
- Department of Medicine and Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (S.V.); (J.A.); (W.D.); (A.S.); (J.D.L.)
| | - Kathleen Li
- Department of Urology, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (K.L.); (A.E.K.)
| | - Ankita Srivastava
- Department of Medicine and Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (S.V.); (J.A.); (W.D.); (A.S.); (J.D.L.)
| | - Joshua De Leon
- Department of Medicine and Foundations of Medicine, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (S.V.); (J.A.); (W.D.); (A.S.); (J.D.L.)
| | - Aaron E. Katz
- Department of Urology, NYU Grossman Long Island School of Medicine, Mineola, NY 11501, USA; (K.L.); (A.E.K.)
| |
Collapse
|
|
4
|
El-Atawy MA, Kebeish R, Almotairy ARZ, Omar AZ. Design, Synthesis, Characterization, and Cytotoxicity of New Pyrazolylmethylene-2-thioxoimidazolidin-4-one Derivatives towards Androgen-Sensitive LNCaP Prostate Cancer Cells. Biomolecules 2024; 14:811. [PMID: 39062524 PMCID: PMC11274643 DOI: 10.3390/biom14070811] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 06/30/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
A new class of pyrazolylmethylene-2-thioxoimidazolidin-4-one derivatives 3a-p were rationally designed and synthesized with the aim of exploring their potential as treatments for prostate cancer. The synthesized compounds 3a-p were biologically analyzed for their anticancer effects against AR+LNCaP, AR-PC-3, and Wi38 cell lines. The observed IC50 values against AR+LNCaP ranged between 10.27 ± 0.14 and 109.72 ± 2.06 µM after 24 h of incubation. Compounds 3i-k, 3m, and 3o-p recorded IC50 values of 05.22 ± 0.12 to 11.75 ± 0.07 µM after 48 h incubation in the presence of 1 nM DHT, with higher selectivity towards AR+LNCaP. Moreover, compounds 3i and 3k significantly induced Caspase 3 accumulation, reduced DNA content at the various stages of the cell cycle, and ultimately caused AR+LNCaP cell growth arrest, as confirmed by cell apoptosis assays. These findings suggest that these analogues of androgen receptor blockers have promising potential for further investigation as effective treatments for prostate cancer.
Collapse
Affiliation(s)
- Mohamed A. El-Atawy
- Chemistry Department, Faculty of Science, Taibah University, Yanbu 46423, Saudi Arabia;
- Chemistry Department, Faculty of Science, Alexandria University, P.O. 426 Ibrahemia, Alexandria 21321, Egypt;
| | - Rashad Kebeish
- Department of Biology, Faculty of Science in Yanbu, Taibah University, Yanbu 46423, Saudi Arabia
- Botany and Microbiology Department, Faculty of Science, Zagazig University, Zagazig 44519, Egypt
| | | | - Alaa Z. Omar
- Chemistry Department, Faculty of Science, Alexandria University, P.O. 426 Ibrahemia, Alexandria 21321, Egypt;
| |
Collapse
|
|
5
|
Taguchi S, Onozawa M, Hinotsu S, Kawai T, Mitomi T, Uno S, Kume H. A multicenter, retrospective observational study investigating baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer treated with primary androgen deprivation therapy. Jpn J Clin Oncol 2023; 53:957-965. [PMID: 37408443 PMCID: PMC10550199 DOI: 10.1093/jjco/hyad068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 06/06/2023] [Indexed: 07/07/2023] Open
Abstract
OBJECTIVE This multicenter, retrospective, observational study investigated baseline characteristics and clinical outcomes in patients with hormone-sensitive prostate cancer who received primary androgen deprivation therapy, using Japan Study Group of Prostate Cancer registry data. METHODS Among patients in the Japan Study Group of Prostate Cancer registry, those who initiated primary androgen deprivation therapy and were aged 20 years or older were enrolled in this study. The primary endpoint was time to disease progression, defined as time from primary androgen deprivation therapy initiation to either prostate-specific antigen or clinical progression. Secondary endpoints included prostate-specific antigen progression-free survival, prostate-specific antigen response (90% or greater reduction from baseline) and distribution of second-line treatment. RESULTS Of the 2494 patients (goserelin, n = 564; leuprorelin, n = 1148; surgical castration, n = 161; degarelix, n = 621), those who received degarelix had higher prostate-specific antigen levels and Gleason scores and were at a more advanced clinical stage than those receiving goserelin or leuprorelin. The median time to disease progression (identical to the prostate-specific antigen progression-free survival result) was not reached for goserelin and leuprorelin, 52.7 months for surgical castration and 54.0 months for degarelix. Although baseline prostate-specific antigen values in the degarelix cohort were higher than those of the leuprorelin or goserelin cohorts, prostate-specific antigen responses were not different among the three cohorts. Regarding second-line treatment, the largest patient group received degarelix followed by leuprorelin (n = 195). CONCLUSIONS This study clarified patient characteristics and long-term effectiveness of primary androgen deprivation therapy in real-world clinical practice. Japanese urologists appear to select appropriate primary androgen deprivation therapy based on patient background and tumour characteristics, with degarelix largely reserved for higher risk patients.
Collapse
Affiliation(s)
- Satoru Taguchi
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Japan Study Group of Prostate Cancer (J-CaP) Research Society, Japan
| | - Mizuki Onozawa
- Japan Study Group of Prostate Cancer (J-CaP) Research Society, Japan
- Department of Urology, International University of Health and Welfare Ichikawa Hospital, Ichikawa, Japan
| | - Shiro Hinotsu
- Japan Study Group of Prostate Cancer (J-CaP) Research Society, Japan
- Department of Biostatistics, Sapporo Medical University, Sapporo, Japan
| | - Taketo Kawai
- Japan Study Group of Prostate Cancer (J-CaP) Research Society, Japan
- Department of Urology, Teikyo University School of Medicine, Tokyo, Japan
| | | | - Satoshi Uno
- Data Science, Astellas Pharma Inc., Tokyo, Japan
| | - Haruki Kume
- Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Japan Study Group of Prostate Cancer (J-CaP) Research Society, Japan
| |
Collapse
|
|
6
|
Abstract
Relugolix (Orgovyx®), an orally active nonpeptide gonadotropin-releasing hormone (GnRH) receptor antagonist that provides rapid testosterone suppression, is indicated in the USA for the treatment of advanced prostate cancer and in the EU for advanced hormone-sensitive prostate cancer. In the pivotal phase III HERO trial in men with advanced prostate cancer, once-daily oral relugolix (with a loading dose on day 1) led to a sustained castration rate over 48 weeks of treatment of > 90%, a rate that was non-inferior to that provided by intramuscular leuprolide depot every 3 months (with an exploratory analysis further indicating the superiority of relugolix over leuprolide). Relugolix was generally well tolerated, having an adverse event profile that is consistent with testosterone suppression. Furthermore, there is evidence that relugolix may be associated with a lower risk of major adverse cardiac events compared with leuprolide. With the ability to provide the rapid testosterone suppression (with no initial surge in testosterone upon treatment initiation) combined with the benefits of oral administration and potentially improved cardiac safety, relugolix presents a valuable treatment option for men with advanced prostate cancer where androgen deprivation therapy is indicated.
Collapse
Affiliation(s)
- Matt Shirley
- Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.
| |
Collapse
|
|
7
|
Wu Q, Qian W, Sun X, Jiang S. Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021. J Hematol Oncol 2022; 15:143. [PMID: 36209184 PMCID: PMC9548212 DOI: 10.1186/s13045-022-01362-9] [Citation(s) in RCA: 116] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 10/02/2022] [Indexed: 11/10/2022] Open
Abstract
The United States Food and Drug Administration (US FDA) has always been a forerunner in drug evaluation and supervision. Over the past 31 years, 1050 drugs (excluding vaccines, cell-based therapies, and gene therapy products) have been approved as new molecular entities (NMEs) or biologics license applications (BLAs). A total of 228 of these 1050 drugs were identified as cancer therapeutics or cancer-related drugs, and 120 of them were classified as therapeutic drugs for solid tumors according to their initial indications. These drugs have evolved from small molecules with broad-spectrum antitumor properties in the early stage to monoclonal antibodies (mAbs) and antibody‒drug conjugates (ADCs) with a more precise targeting effect during the most recent decade. These drugs have extended indications for other malignancies, constituting a cancer treatment system for monotherapy or combined therapy. However, the available targets are still mainly limited to receptor tyrosine kinases (RTKs), restricting the development of antitumor drugs. In this review, these 120 drugs are summarized and classified according to the initial indications, characteristics, or functions. Additionally, RTK-targeted therapies and immune checkpoint-based immunotherapies are also discussed. Our analysis of existing challenges and potential opportunities in drug development may advance solid tumor treatment in the future.
Collapse
Affiliation(s)
- Qing Wu
- School of Medical Imaging, Hangzhou Medical College, Hangzhou, 310053 Zhejiang China
| | - Wei Qian
- Department of Radiology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, 310009 Zhejiang China
| | - Xiaoli Sun
- Department of Radiation Oncology, School of Medicine, The First Affiliated Hospital, Zhejiang University, Hangzhou, 310003 Zhejiang China
| | - Shaojie Jiang
- School of Medical Imaging, Hangzhou Medical College, Hangzhou, 310053 Zhejiang China
| |
Collapse
|
|
8
|
Pyrgidis N, Hatzichristodoulou G, Sokolakis I. [Treatment of advanced hormone-sensitive prostate cancer using degarelix]. Urologe A 2021; 61:63-67. [PMID: 34907463 DOI: 10.1007/s00120-021-01735-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/24/2021] [Indexed: 10/19/2022]
Affiliation(s)
- Nikolaos Pyrgidis
- Urologische Klinik, Martha-Maria-Krankenhaus Nürnberg, Stadenstr. 58, 90491, Nürnberg, Deutschland
| | | | - Ioannis Sokolakis
- Urologische Klinik, Martha-Maria-Krankenhaus Nürnberg, Stadenstr. 58, 90491, Nürnberg, Deutschland. .,UroEvidence@Deutsche Gesellschaft für Urologie, Berlin, Deutschland.
| |
Collapse
|
|
9
|
Chen K, Jiang K, Tang L, Chen X, Hu J, Sun F. Analysis of Clinical Trials on Therapies for Prostate Cancer in Mainland China and Globally from 2010 to 2020. Front Oncol 2021; 11:647110. [PMID: 34084744 PMCID: PMC8167212 DOI: 10.3389/fonc.2021.647110] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Accepted: 04/12/2021] [Indexed: 12/23/2022] Open
Abstract
The overall aging of the world population has contributed to the continuous upward trend in the incidence of prostate cancer (PC). Trials on PC therapy have been extensively performed, but no study has analyzed the overall trends and characteristics of these trials, especially for those carried out in China. This study aimed to provide insights on the future direction of drug development in PC, thus supplying essential supportive data for stakeholders, including researchers, patients, investors, clinicians, and pharmaceutical industry. The details of the clinical trials of drug therapies for PC during January 1, 2010, to January 1, 2020, were collected from Pharmaprojects. A total of 463 clinical trials on different therapies with 132 different drugs were completed. The long-acting endocrine therapy with few side effects, radiotherapy combined with immune checkpoint inhibitors, gene-targeted chemotherapeutics, and novel immunotherapeutic products changed the concept of PC treatment. In mainland China, 31 trials with 19 drugs have been completed in the 10 assessment years. China has initiated a few trials investigating a limited number of drug targets, centered in a markedly uneven geographical distribution of leading clinical trial units; hence, the development of PC drugs has a long way to go. Given the large patient pool, China deserves widespread attention for PC drug research and development. These findings might have a significant impact on scientific research and industrial investment.
Collapse
Affiliation(s)
- Kun Chen
- NHC Key Laboratory of Pulmonary Immune-Related Diseases, Guizhou Provincial People's Hospital, Guiyang, China
| | - Kehua Jiang
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China
| | - Lannan Tang
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China
| | - Xiaolong Chen
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China
| | - Jianxin Hu
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China
| | - Fa Sun
- Department of Urology, Guizhou Provincial People's Hospital, Guiyang, China
| |
Collapse
|
|
10
|
Kirby MG, Allchorne P, Appanna T, Davey P, Gledhill R, Green JSA, Greene D, Rosario DJ. Prescription switching: Rationales and risks. Int J Clin Pract 2020; 74:e13429. [PMID: 31573733 DOI: 10.1111/ijcp.13429] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2019] [Accepted: 09/21/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Therapeutic drug switching is commonplace across a broad range of indications and, within a drug class, is often facilitated by the availability of multiple drugs considered equivalent. Such treatment changes are often considered to improve outcomes via better efficacy or fewer side effects, or to be more cost-effective. Drug switching can be both appropriate and beneficial for several reasons; however, switching can also be associated with negative consequences. AIM To consider the impact of switching in two situations: the use of statins as a well-studied example of within-class drug switching, and gonadotropin-releasing hormone (GnRH)-targeting drug switching as an example of cross-class switching. RESULTS With the example of statins, within-class switching may be justified to reduce side effects, although the decision to switch is often also driven by the lower cost of generic formulations. With the example of GnRH agonists/antagonists, switching often occurs without the realisation that these drugs belong to different classes, with potential clinical implications. CONCLUSION Lessons emerging from these examples will help inform healthcare practitioners who may be considering switching drug prescriptions.
Collapse
Affiliation(s)
| | - Paula Allchorne
- Barts Health NHS Trust, The Royal London Hospital, London, UK
| | | | | | | | - James S A Green
- Barts Health NHS Trust, The Royal London Hospital, London, UK
| | | | | |
Collapse
|
|
11
|
Vlachostergios PJ, Paddock M, Molina AM. Molecular Targeted Therapies of Prostate Cancer. MOLECULAR PATHOLOGY LIBRARY 2018. [DOI: 10.1007/978-3-319-64096-9_29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
|
|
12
|
Dellis A, Papatsoris A. Therapeutic outcomes of the LHRH antagonists. Expert Rev Pharmacoecon Outcomes Res 2017; 17:481-488. [DOI: 10.1080/14737167.2017.1375855] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Affiliation(s)
- Athanasios Dellis
- University Department of Urology, Sismanglio General Hospital, Athens, Greece
- University Department of Surgery, Areteion Hospital, Athens, Greece
| | | |
Collapse
|
|
13
|
GnRH Antagonist: a New and an Effective Way of Treatment of Advanced Prostate Cancer. Indian J Surg Oncol 2017; 8:385-388. [DOI: 10.1007/s13193-016-0611-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2016] [Accepted: 11/18/2016] [Indexed: 10/20/2022] Open
|
|
14
|
Fang C, Wu CL, Liu SS, Ge L, Bai JL. Efficacy, safety, and dose comparison of degarelix for the treatment of prostate cancer: A systematic review and meta-analysis. World J Meta-Anal 2016; 4:69-76. [DOI: 10.13105/wjma.v4.i3.69] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2016] [Revised: 03/14/2016] [Accepted: 04/22/2016] [Indexed: 02/05/2023] Open
Abstract
AIM: To conduct a systematic review and meta-analysis into the efficacy, safety, and dosage regimens of degarelix for treating prostate cancer (PCa).
METHODS: PubMed, EMBASE, the Cochrane Library, and Web of Science was systematically searched to identify randomized controlled trials (RCTs) comparing degarelix (240/80 mg vs 240/160 mg) to the gonadotropin-releasing hormone agonists, goserelin and leuprolide, for the treatment of PCa. Two independent reviewers screened putative studies, assessed the risk of bias, and then extracted pertinent data. Analyses were performed using Review Manager 5.2.
RESULTS: Seven papers from six RCTs, involving 1204 patients, were identified. The present meta-analysis showed that treatment with 240/160 mg degarelix is more effective and has fewer adverse events (AEs) relative to conventional 240/80 mg regimen. Degarelix significantly decreased International Prostate Symptom Scores [standardized mean differences (SMD) = -0.32, 95%CI: -0.51 to -0.12, P = 0.02] and caused fewer AEs (SMD = -0.28, 95%CI: -0.48 to -0.07, P = 0.008) than goserelin. Degarelix suppressed testosterone and prostate-specific antigen significantly faster than leuprolide.
CONCLUSION: Degarelix is a useful option in the treatment of advanced PCa. Degarelix 240/160 mg regimen was superior to a 240/80 mg regimen. More rigorously designed RCTs are urgently needed to confirm the efficacy of degarelix.
Collapse
|
|
15
|
Qi P, Chen M, Zhang LX, Song RX, He ZH, Wang ZP. A Meta-Analysis and Indirect Comparison of Endothelin A Receptor Antagonist for Castration-Resistant Prostate Cancer. PLoS One 2015; 10:e0133803. [PMID: 26192308 PMCID: PMC4508042 DOI: 10.1371/journal.pone.0133803] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2015] [Accepted: 06/30/2015] [Indexed: 01/08/2023] Open
Abstract
Background Endothelin A (ET-A) receptor antagonists including zibotentan and atrasentan, have been suggested as a treatment for castration-resistant prostate cancer (CRPC). Our aim was to conduct a meta-analysis and indirect comparison to assess the efficacy and safety of ET-A receptor antagonists for treatment of CRPC. Methods We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science from inception to November 2014 to identify randomized controlled trials (RCTs) which assessed ET-A receptor antagonists for treatment of CRPC. Meta-analysis was conducted by STATA version 12.0 software. Results Eight RCTs were identified, involving 6,065 patients. The results of direct comparison showed that compared with placebo, there was no statistically significant difference in the improvement of progression-free survival (PFS), overall survival (OS), time to disease progression (TTP), and total adverse events (AEs) with ET-A receptor antagonist treatment for CRPC. The results of ET-A receptor antagonists plus docetaxel versus docetaxel alone were similar. The indirect comparisons showed that there were no significant differences between zibotentan plus docetaxel versus atrasentan plus docetaxel when compared with docetaxel alone or zibotentan versus atrasenta compared with placebo in the improvement of PFS, OS, TTP, and total adverse events. Conclusions There were no significant benefits for ET-A receptor antagonists with or without docetaxel in the improvement of PFS, OS, TTP, and overall AEs. And there were no significant differences between zibotentan and atrasentan. Single-agent docetaxel should remain as one of the standard treatments.
Collapse
Affiliation(s)
- Ping Qi
- Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China
- Department of Clinical Laboratory, The Second Hospital of Lanzhou University, Lanzhou 730030, China
| | - Ming Chen
- Department of Urology, GanSu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China
| | - Li-xiu Zhang
- Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China
| | - Rui-xia Song
- Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China
- Key Laboratory of Urological Diseases in Gansu Province, Lanzhou 730030, China
| | - Zhen-hua He
- Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China
- Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou 730030, China
| | - Zhi-ping Wang
- Institute of Urology, The Second Hospital of Lanzhou University, Lanzhou 730030, China
- Key Laboratory of Urological Diseases in Gansu Province, Lanzhou 730030, China
- * E-mail:
| |
Collapse
|
|
16
|
Sistigu A, Manic G, Obrist F, Vitale I. Trial watch - inhibiting PARP enzymes for anticancer therapy. Mol Cell Oncol 2015; 3:e1053594. [PMID: 27308587 DOI: 10.1080/23723556.2015.1053594] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2015] [Revised: 05/16/2015] [Accepted: 05/18/2015] [Indexed: 12/25/2022]
Abstract
Poly(ADP-ribose) polymerases (PARPs) are a members of family of enzymes that catalyze poly(ADP-ribosyl)ation (PARylation) and/or mono(ADP-ribosyl)ation (MARylation), two post-translational protein modifications involved in crucial cellular processes including (but not limited to) the DNA damage response (DDR). PARP1, the most abundant family member, is a nuclear protein that is activated upon sensing distinct types of DNA damage and contributes to their resolution by PARylating multiple DDR players. Recent evidence suggests that, along with DDR, activated PARP1 mediates a series of prosurvival and proapoptotic processes aimed at preserving genomic stability. Despite this potential oncosuppressive role, upregulation and/or overactivation of PARP1 or other PARP enzymes has been reported in a variety of human neoplasms. Over the last few decades, several pharmacologic inhibitors of PARP1 and PARP2 have been assessed in preclinical and clinical studies showing potent antineoplastic activity, particularly against homologous recombination (HR)-deficient ovarian and breast cancers. In this Trial Watch, we describe the impact of PARP enzymes and PARylation in cancer, discuss the mechanism of cancer cell killing by PARP1 inactivation, and summarize the results of recent clinical studies aimed at evaluating the safety and therapeutic profile of PARP inhibitors in cancer patients.
Collapse
Affiliation(s)
| | - Gwenola Manic
- Regina Elena National Cancer Institute , Rome, Italy
| | - Florine Obrist
- Université Paris-Sud/Paris XI, Le Kremlin-Bicêtre, France; INSERM, UMRS1138, Paris, France; Equipe 11 labelisée par la Ligue Nationale contre le Cancer, Center de Recherche des Cordeliers, Paris, France; Gustave Roussy Cancer Campus, Villejuif, France
| | - Ilio Vitale
- Regina Elena National Cancer Institute, Rome, Italy; Department of Biology, University of Rome "TorVergata", Rome, Italy
| |
Collapse
|
|
17
|
Baker H. Choosing a prostate cancer drug. ACTA ACUST UNITED AC 2014; 23:S14, S16. [PMID: 25203849 DOI: 10.12968/bjon.2014.23.sup16.s14] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Hilary Baker
- Lead Uro-oncology CNS, University College London Hospitals, NHS Foundations Trust
| |
Collapse
|