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Ghijben P, Petrie D, Zavarsek S, Chen G, Lancsar E. Behavioral Responses to Healthcare Funding Decisions and Their Impact on Value for Money: Evidence From Australia. HEALTH ECONOMICS 2025; 34:1239-1254. [PMID: 40098603 PMCID: PMC12166537 DOI: 10.1002/hec.4958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2023] [Revised: 02/23/2025] [Accepted: 02/27/2025] [Indexed: 03/19/2025]
Abstract
Value for money is fundamental to health insurance schemes given insurers must choose which treatments to fund. Assessing value for money ex ante is challenging, however, because costs and outcomes depend on how treatments are used. Estimates often rely on evidence from early randomized controlled trials conducted prior to regulatory approval, where provider and patient behaviors are tightly controlled. This approach ignores how different supply conditions and incentives in practice influence behaviors. This paper considers how provider and patient incentives can differ between trial and practice settings and analyses how healthcare use changed when new prostate cancer treatments were funded on the public health insurance scheme in Australia. We find evidence that doctors treated patients with worse prognosis compared to the trials, patients ceased prior treatment and switched to the new treatments earlier than expected, and treatment duration was longer than expected. These and other behavioral responses reduced value for money ex post. Our findings suggest that health insurers should carefully consider the supply conditions and incentives in practice when funding new treatments.
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Affiliation(s)
- Peter Ghijben
- Centre for Health EconomicsMonash Business SchoolMonash UniversityCaulfieldAustralia
| | - Dennis Petrie
- Centre for Health EconomicsMonash Business SchoolMonash UniversityCaulfieldAustralia
| | - Silva Zavarsek
- Deakin Health EconomicsSchool of Health and Social DevelopmentInstitute for Health TransformationDeakin UniversityBurwoodAustralia
| | - Gang Chen
- Centre for Health EconomicsMonash Business SchoolMonash UniversityCaulfieldAustralia
| | - Emily Lancsar
- Department of Health Economics Wellbeing and SocietyCollege of Health & MedicineThe Australian National UniversityActonAustralia
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Korake S, Bothiraja C, Pawar A. Design, development, and in-vitro/in-vivo evaluation of Docetaxel-loaded PEGylated Solid Lipid Nanoparticles in Prostate Cancer Therapy. Eur J Pharm Biopharm 2023:S0939-6411(23)00142-X. [PMID: 37270157 DOI: 10.1016/j.ejpb.2023.05.020] [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: 01/24/2023] [Revised: 05/25/2023] [Accepted: 05/27/2023] [Indexed: 06/05/2023]
Abstract
Docetaxel (DOC) is a potent anticancer molecule widely used to treat various cancers. However, its therapeutic efficacy as a potential anticancer agent has been limited owing to poor aqueous solubility, short circulation time, rapid reticuloendothelial system uptake, and high renal clearance, which consecutively showed poor bioavailability. In the present investigation, we developed polyethylene glycol (PEG) decorated solid lipid nanoparticles (SLN) using the solvent diffusion method to increase the biopharmaceutical properties of DOC. PEG monostearate (SA-PEG2000) was initially synthesized and characterized using various analytical techniques. Afterwards, DOC-loaded SLN was synthesized with and without SA-PEG2000and systematically characterized for in-vitro and in-vivo properties. Spherical-shaped SA-PEG2000-DOC SLN showed hydrodynamic diameter and zeta potential of 177 nm and -13 mV, respectively. During the in-vitro release study DOC-loaded SLN showed a controlledrelease of approximately 54.35 % ±5.46 within 12 h with Higuchi release kinetics in the tumor microenvironment (pH 5.5).In an in-vitro cytotoxicity study,SA-PEG2000-DOC SLN showedsignificantlylower IC50values(p < 0.001)compared to DOC-SLN and DOC aloneagainst prostate cancer cell lines (PC-3). Similarly, an in-vitro cellular uptake study showed a significant increase in intracellular DOC concentration for SA-PEG2000-DOC SLN. Additionally, inin-vivostudies,PEGylated SLN of DOC showed around 2- and 15-fold increase in the maximum concentration of drug (Cmax) and area under the curve (AUC), respectively, as compared to plain DOC solution due to the uniquehydrophilicity and hydrophobicity balance and electrical neutrality of specially designed PEG architect. The biological half-life (t1/2) and mean residence time (MRT) was found to increase from 8.55 and 11.43 to 34.96 and 47.68 h, respectively, with SA-PEG2000-DOC SLN. Moreover, the bio-distribution study indicates high DOC concentration in the plasma which signifies the more pronounced blood residence time of SA-PEG2000-DOC SLN. In a nutshell, SA-PEG2000-DOC SLNwasfound to bea promising and efficient drug delivery platform for the management of Metastatic Prostate cancer.
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Affiliation(s)
- Swati Korake
- Department of Pharmaceutics, Bharati Vidyapeeth Deemed to Be University (BVDU) Poona College of Pharmacy, Pune 411038, India
| | - C Bothiraja
- Department of Pharmaceutics, Bharati Vidyapeeth Deemed to Be University (BVDU) Poona College of Pharmacy, Pune 411038, India
| | - Atmaram Pawar
- Department of Pharmaceutics, Bharati Vidyapeeth Deemed to Be University (BVDU) Poona College of Pharmacy, Pune 411038, India.
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Zhang M, Chen F, Sun X, Huang Y, Zeng Y, Chen J, Wu S, Xu C. Sympathetic β2-adrenergic receptor blockade overcomes docetaxel resistance in prostate cancer. Biochem Biophys Res Commun 2023; 657:69-79. [PMID: 36989842 DOI: 10.1016/j.bbrc.2023.03.046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/03/2023] [Accepted: 03/16/2023] [Indexed: 03/30/2023]
Abstract
PURPOSE Due to the limited effective therapies, resistance to docetaxel is ordinarily fatal and remains a critical clinical challenge.β2-adrenergic receptor(β2-AR)can promote the metastasis and invasion of prostate cancer, but the role in chemotherapy-resistant prostate cancer remains unclear. METHODS By downloading the GEO database in NCBI, the expression of β2-AR in different prostate tissues was analyzed. We constructed docetaxel-resistant prostate cancer cell lines by the method of dose-escalation. LC3B-labeled stable cells and shAtg5 knockdown stable cells were constructed by lentivirus infection. The molecular mechanism of β2-AR affecting docetaxel sensitivity through apoptosis and autophage were investigated by flow cytometry, mitochondrial membrane potential and western blot. Then we detected the interaction between autophagy and apoptotic by performing immunoprecipitation assay. RESULTS We show that restraining the activity of β2-AR sensitized the cell response and reduced the resistance to docetaxel. The mechanism involves the regulation of β2-AR in the cellular response to docetaxel through apoptosis and autophagy via caspase signaling and Atg5/AMPK/mTOR pathway as well as the effect of β2-AR on the crosstalk between apoptosis and autophagy via p38 MAPK and JNK/c-Jun/FOXO3a signaling pathways. CONCLUSION Our data demonstrate that β2-AR inhibitor-induced autophagy and apoptosis contribute to the effectiveness responses to docetaxel in castration-resistant prostate cancer, and in combination with pharmacological agents of β2-AR and autophagy inhibitors may provide a potential therapeutic strategy to enhance the limited capacity of docetaxel to control castration-resistant prostate cancer.
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Affiliation(s)
- Mi Zhang
- Institution of Life Science, Chongqing Medical University, Chongqing, China
| | - Fangfang Chen
- Institution of Life Science, Chongqing Medical University, Chongqing, China
| | - Xueqing Sun
- Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yanping Huang
- Institution of Life Science, Chongqing Medical University, Chongqing, China
| | - Yan Zeng
- Institution of Life Science, Chongqing Medical University, Chongqing, China
| | - Jinying Chen
- Institution of Life Science, Chongqing Medical University, Chongqing, China
| | - Shiqi Wu
- Institution of Life Science, Chongqing Medical University, Chongqing, China
| | - Chen Xu
- Institution of Life Science, Chongqing Medical University, Chongqing, China.
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Chen H, Luo J, Chen S, Shi B, Zheng X, Ji H, Zhang X, Yin Y, Du K, Ding J, Yu Y. Non-drug efflux function of ABCC5 promotes enzalutamide resistance in castration-resistant prostate cancer via upregulation of P65/AR-V7. Cell Death Discov 2022; 8:241. [PMID: 35504877 PMCID: PMC9065095 DOI: 10.1038/s41420-022-00951-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2021] [Revised: 02/24/2022] [Accepted: 03/14/2022] [Indexed: 11/08/2022] Open
Abstract
Drug resistance is responsible for castration-resistant prostate cancer (CRPC)-associated mortality. While ATP binding cassette subfamily C member 5 (ABCC5) has been reported to regulate multiple drug resistance, its drug-efflux function may not be the main reason underlying resistance to enzalutamide, an androgen receptor inhibitor. Here, we aimed to determine whether the non-drug efflux function of ABCC5 affects enzalutamide resistance. The ABCC5 expression data in patients with prostate cancer (PCa) were retrieved from The Cancer Genome Atlas and Gene Expression Omnibus, and their correlation with disease prognosis was analyzed. Immunohistochemical staining was performed on a cohort of 80 patient samples. Proliferation of enzalutamide-resistant 22RV1 and C4-2B cells was investigated using CCK-8, EdU, and colony formation assays. The effect of ABCC5 silencing on enzalutamide resensitization was evaluated in vitro and in vivo. Functional assays indicated that ABCC5 depletion resensitized enzalutamide-resistant cells to inhibit cell growth and impeded xenograft tumor proliferation. Mechanistically, luciferase and ChIP assays confirmed that P65 regulated AR expression and activity by binding to its promoter, while ABCC5-mediated resistance effected by AR-V7 (one of the widely studied AR splicing variants that meditate AR antagonist resistance) upregulation could be reversed by P65 knockdown. Furthermore, activation of the NF-κB pathway reversed the effects of ABCC5 knockdown by extra AR-V7 expression. Thus, ABCC5 might be a novel target for enzalutamide-resistant CRPC treatment.
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Affiliation(s)
- Haojie Chen
- Department of Urology, School of Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200092, P. R. China
| | - Jia Luo
- Department of Ophthalmology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China
| | - Shaojun Chen
- Department of Urology, School of Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200092, P. R. China
| | - Bowen Shi
- Department of Urology, School of Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200092, P. R. China
| | - Xiaocui Zheng
- Department of Obstetrics and Gynecology, Shanghai Jiao Tong University School of Medicine Xinhua Hospital, Shanghai, China
| | - Haiying Ji
- Department of Anesthesiology and SICU, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200092, China
| | - Xiaoqian Zhang
- Department of Obstetrics and Gynecology, Shanghai Jiao Tong University School of Medicine Xinhua Hospital, Shanghai, China
| | - Yujia Yin
- Department of Obstetrics and Gynecology, Shanghai Jiao Tong University School of Medicine Xinhua Hospital, Shanghai, China
| | - Kun Du
- Department of Laboratory Medicine, Shanghai Jiao Tong University School of Medicine Xinhua Hospital, Shanghai, China.
| | - Jie Ding
- Department of Urology, School of Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200092, P. R. China.
| | - Yongjiang Yu
- Department of Urology, School of Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, 200092, P. R. China.
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Gu H, Duan Z. Silencing of circDPP4 suppresses cell progression of human prostate cancer and enhances docetaxel cytotoxicity through regulating miR-564/ZIC2 axis. J Gene Med 2021; 24:e3403. [PMID: 34904327 DOI: 10.1002/jgm.3403] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2021] [Revised: 11/22/2021] [Accepted: 11/25/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Circular RNA derived from dipeptidyl peptidase 4 (circDPP4; ID: hsa_circ_0056881) is one top increased circRNA in prostate cancer (PC), and docetaxel (DTX)-based chemotherapy is the primary therapeutic choice for PC. However, its repertoire in PC development and chemoresistance remains to be documented. METHODS Expression of circDPP4, microRNA (miR)-564 and zinc finger of the cerebellum 2 (ZIC2) was detected by real-time quantitative PCR and western blotting; the direct interaction was validated by RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation. Cell progression was measured by cell counting kit-8, colony formation assay, flow cytometry, Transwell assay, xenograft experiment, and immunohistochemistry. DTX cytotoxicity was confirmed by MTT cell viability assay. RESULTS Expression of circDPP4 is upregulated in PC tumors from 60 patients and PC cell lines, and higher circDPP4 might predict poor overall survival. Decreasing circDPP4 suppresses cell proliferation, colony formation, migration/invasion, and 50% inhibitory concentration of DTX in PC cells, and promotes apoptosis rate. Both overexpressing miR-564 and inhibiting ZIC2 could imitate those effects, while inhibiting miR-564 and restoring ZIC2 could separately counteract that. Mechanistically, circDPP4 functions as miR-564 sponge and regulates the expression of ZIC2, a target gene for miR-564. Tumor growth is retarded by silencing circDPP4, accompanied with elevated miR-564 and attenuated Ki-67 and ZIC2. CONCLUSION Blocking circDPP4 antagonizes cell progression of PC and contributes to in vitro DTX cytotoxicity via regulating miR-564/ZIC2 axis, at least. This study suggests circDPP4 as a potential biomarker and target for PC.
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Affiliation(s)
- Hao Gu
- Department of Urinary Surgery, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
| | - Zhongqi Duan
- Department of Urinary Surgery, Xi'an People's Hospital (Xi'an Fourth Hospital), Xi'an, China
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Farah E, Li C, Cheng L, Kong Y, Lanman NA, Pascuzzi P, Lorenz GR, Zhang Y, Ahmad N, Li L, Ratliff T, Liu X. NOTCH signaling is activated in and contributes to resistance in enzalutamide-resistant prostate cancer cells. J Biol Chem 2019; 294:8543-8554. [PMID: 30940724 DOI: 10.1074/jbc.ra118.006983] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 03/28/2019] [Indexed: 12/17/2022] Open
Abstract
Prostate cancer is the second leading cause of cancer death among men in the United States. The androgen receptor (AR) antagonist enzalutamide is a Food and Drug Administration-approved drug for treatment of patients with late-stage prostate cancer and is currently under clinical study for early-stage prostate cancer treatment. After a short positive response period, tumors will develop drug resistance. In this study using RNA-Seq and bioinformatics analyses, we observed that NOTCH signaling is a deregulated pathway in enzalutamide-resistant cells. NOTCH2 and c-MYC gene expression positively correlated with AR expression in samples from patient with hormone refractory disease in which AR expression levels correspond to those typically observed in enzalutamide resistance. Cleaved NOTCH1, HES1 (Hes family BHLH transcription factor 1), and c-MYC protein expression levels are elevated in two enzalutamide-resistant cell lines, MR49F and C4-2R, indicating NOTCH signaling activation. Moreover, inhibition of the overexpressed ADAM metallopeptidase domain 10 (ADAM10) in the resistant cells induces an exclusive reduction in cleaved NOTCH1 expression. Furthermore, exposure of enzalutamide-resistant cells to both PF-03084014 and enzalutamide increased cell death, decreased colony formation ability, and resensitized cells to enzalutamide. Knockdown of NOTCH1 in C4-2R increased enzalutamide sensitivity by decreasing cell proliferation and increasing cleaved PARP expression. In a 22RV1 xenograft model, PF-03084014 and enzalutamide decreased tumor growth through reducing cell proliferation and increasing apoptosis. These results indicate that NOTCH1 signaling may contribute to enzalutamide resistance in prostate cancer, and inhibition of NOTCH signaling can resensitize resistant cells to enzalutamide.
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Affiliation(s)
- Elia Farah
- Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907
| | - Chaohao Li
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana 47907
| | - Lijun Cheng
- Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio 43210
| | - Yifan Kong
- Department of Animal Sciences, Purdue University, West Lafayette, Indiana 47907
| | - Nadia A Lanman
- Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907; Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana 47907
| | - Pete Pascuzzi
- Purdue University Libraries, Purdue University, West Lafayette, Indiana 47907
| | | | - Yanquan Zhang
- Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907
| | - Nihal Ahmad
- Department of Dermatology, University of Wisconsin, Madison, Wisconsin 53715
| | - Lang Li
- Department of Biomedical Informatics, The Ohio State University, Columbus, Ohio 43210
| | - Tim Ratliff
- Center for Cancer Research, Purdue University, West Lafayette, Indiana 47907; Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana 47907
| | - Xiaoqi Liu
- Department of Biochemistry, Purdue University, West Lafayette, Indiana 47907; Department of Comparative Pathobiology, Purdue University, West Lafayette, Indiana 47907; Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, Kentucky 40536.
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Rottach AM, Ahrend H, Martin B, Walther R, Zimmermann U, Burchardt M, Stope MB. Cabazitaxel inhibits prostate cancer cell growth by inhibition of androgen receptor and heat shock protein expression. World J Urol 2019; 37:2137-2145. [PMID: 30603780 DOI: 10.1007/s00345-018-2615-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 12/20/2018] [Indexed: 02/07/2023] Open
Abstract
PURPOSE Cabazitaxel, a semi-synthetic taxane of the third generation, inhibits prostate cancer (PC) cell growth by affecting the microtubule architecture. Since cabazitaxel has also been demonstrated to inhibit androgen receptor (AR) functionality, AR and AR-associated heat shock protein (HSP) expressions in the presence of cabazitaxel were characterized. METHODS AR and HSP expressions were assessed via Western blotting utilizing a PC-cell-line in vitro system incubated with cabazitaxel. RESULTS Incubation experiments with 0.3 nM cabazitaxel exhibited significantly reduced levels of AR and the AR-associated factors HSP90α, HSP40, and HSP70/HSP90 organising protein. Furthermore, expression of the anti-apoptotic factor HSP60 was suppressed. In contrast to other anticancer compounds, cabazitaxel did not alter the cytoprotective chemoresistance factor HSP27. CONCLUSIONS Despite the deregulation of microtubule organisation, cabazitaxel has been shown to suppress the expression of HSP. Very notably, and may be as a result of down-regulated HSP, cabazitaxel additionally inhibits the expression of the AR in AR-positive PC cells. Thus, cabazitaxel bears an additional anti-proliferative activity which is at least in part specific for PC cells.
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Affiliation(s)
- Anja-Martina Rottach
- Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Hannes Ahrend
- Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Benedikt Martin
- Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Reinhard Walther
- Department of Medical Biochemistry and Molecular Biology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Uwe Zimmermann
- Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Martin Burchardt
- Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany
| | - Matthias B Stope
- Department of Urology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475, Greifswald, Germany.
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Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol 2018; 19:975-986. [PMID: 29880291 DOI: 10.1016/s1470-2045(18)30365-6] [Citation(s) in RCA: 297] [Impact Index Per Article: 42.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2018] [Revised: 05/04/2018] [Accepted: 05/08/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND Patients with metastatic castration-resistant prostate cancer and homologous recombination repair (HRR) mutations have a better response to treatment with the poly(ADP-ribose) polymerase inhibitor olaparib than patients without HRR mutations. Preclinical data suggest synergy between olaparib and androgen pathway inhibitors. We aimed to assess the efficacy of olaparib plus the androgen pathway inhibitor abiraterone in patients with metastatic castration-resistant prostate cancer regardless of HRR mutation status. METHODS We carried out this double-blind, randomised, placebo-controlled phase 2 trial at 41 urological oncology sites in 11 countries across Europe and North America. Eligible male patients were aged 18 years or older with metastatic castration-resistant prostate cancer who had previously received docetaxel and were candidates for abiraterone treatment. Patients were excluded if they had received more than two previous lines of chemotherapy, or had previous exposure to second-generation antihormonal drugs. Patients were randomly assigned (1:1) using an interactive voice or web response system, without stratification, to receive oral olaparib 300 mg twice daily or placebo. All patients received oral abiraterone 1000 mg once daily and prednisone or prednisolone 5 mg twice daily. Patients and investigators were masked to treatment allocation. The primary endpoint was investigator-assessed radiographic progression-free survival (rPFS; based on Response Evaluation Criteria in Solid Tumors version 1.1 and Prostate Cancer Clinical Trials Working Group 2 criteria). Efficacy analyses were done in the intention-to-treat population, which included all randomly assigned patients, and safety analyses included all patients who received at least one dose of olaparib or placebo. This trial is registered with ClinicalTrials.gov, number NCT01972217, and is no longer recruiting patients. FINDINGS Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. Of those, 142 patients were randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). The clinical cutoff date for the final analysis was Sept 22, 2017. Median rPFS was 13·8 months (95% CI 10·8-20·4) with olaparib and abiraterone and 8·2 months (5·5-9·7) with placebo and abiraterone (hazard ratio [HR] 0·65, 95% CI 0·44-0·97, p=0·034). The most common grade 1-2 adverse events were nausea (26 [37%] patients in the olaparib group vs 13 [18%] patients in the placebo group), constipation (18 [25%] vs eight [11%]), and back pain (17 [24%] vs 13 [18%]). 38 (54%) of 71 patients in the olaparib and abiraterone group and 20 (28%) of 71 patients in the placebo and abiraterone group had grade 3 or worse adverse events, including anaemia (in 15 [21%] of 71 patients vs none of 71), pneumonia (four [6%] vs three [4%]), and myocardial infarction (four [6%] vs none). Serious adverse events were reported by 24 (34%) of 71 patients receiving olaparib and abiraterone (seven of which were related to treatment) and 13 (18%) of 71 patients receiving placebo and abiraterone (one of which was related to treatment). One treatment-related death (pneumonitis) occurred in the olaparib and abiraterone group. INTERPRETATION Olaparib in combination with abiraterone provided clinical efficacy benefit for patients with metastatic castration-resistant prostate cancer compared with abiraterone alone. More serious adverse events were observed in patients who received olaparib and abiraterone than abiraterone alone. Our data suggest that the combination of olaparib and abiraterone might provide an additional clinical benefit to a broad population of patients with metastatic castration-resistant prostate cancer. FUNDING AstraZeneca.
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9
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Investigating BRCA Mutations: A Breakthrough in Precision Medicine of Castration-Resistant Prostate Cancer. Target Oncol 2017; 11:569-577. [PMID: 27402433 DOI: 10.1007/s11523-016-0450-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Despite the development of novel effective therapeutic strategies, metastatic castration-resistant prostate cancer (mCRPC) remains a disease with a lethal course and a high biological and molecular heterogeneity. To date, germline mutations in the BRCA gene represent one of the main risk factors for developing prostate cancer, with a strong association with aggressive phenotype and poor clinical outcomes. A better understanding of the genomic landscape of prostate cancer has strengthened the idea that "synthetic lethality" of this disease might be useful in cancer-drug discovery, focusing on agents such as platinum compounds and poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPi). In this review, we summarize the main data available on BRCA mutations and discuss the clinical implications of these genomic aberrations in the management of prostate cancer, stressing the need to identify prognostic and predictive biomarkers and to deeply understand the mechanisms of treatment resistance, in order to maximize personalized medicine protocols and therefore clinical benefit.
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10
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Miao L, Yang L, Li R, Rodrigues DN, Crespo M, Hsieh JT, Tilley WD, de Bono J, Selth LA, Raj GV. Disrupting Androgen Receptor Signaling Induces Snail-Mediated Epithelial–Mesenchymal Plasticity in Prostate Cancer. Cancer Res 2017; 77:3101-3112. [DOI: 10.1158/0008-5472.can-16-2169] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2016] [Revised: 10/04/2016] [Accepted: 03/07/2017] [Indexed: 11/16/2022]
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11
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Winters-Stone KM, Moe E, Graff JN, Dieckmann NF, Stoyles S, Borsch C, Alumkal JJ, Amling CL, Beer TM. Falls and Frailty in Prostate Cancer Survivors: Current, Past, and Never Users of Androgen Deprivation Therapy. J Am Geriatr Soc 2017; 65:1414-1419. [PMID: 28263373 DOI: 10.1111/jgs.14795] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2016] [Revised: 11/29/2016] [Accepted: 11/29/2016] [Indexed: 11/30/2022]
Abstract
OBJECTIVES To compare the prevalence of and association between falls and frailty of prostate cancer survivors (PCSs) who were current, past or never users of androgen deprivation therapy (ADT). DESIGN Cross-sectional. SETTING Mail and electronic survey. PARTICIPANTS PCSs (N = 280; mean age 72 ± 8). MEASUREMENTS Cancer history, falls, and frailty status (robust, prefrail, frail) using traditionally defined and obese phenotypes. RESULTS Current (37%) or past (34%) ADT users were more than twice as likely to have fallen in the previous year as never users (15%) (P = .002). ADT users had twice as many recurrent falls (P < .001) and more fall-related injuries than unexposed men (P = .01). Current (43%) or past (40%) ADT users were more likely to be classified as prefrail or frail than never users (15%) (P < .001), and the prevalence of combined obese frailty + prefrailty was even greater in current (59%) or past (62%) ADT users than never users (25%) (P < .001). Traditional and obese frailty significantly increased the likelihood of reporting falls in the previous year (odds ratio (OR) = 2.15, 95% CI = 1.18-3.94 and OR = 2.97, 95% CI = 1.62-5.58, respectively) and was also associated with greater risk of recurrent falls (OR = 3.10, 95% CI = 1.48-6.5 and OR = 3.99, 95% CI = 1.79-8.89, respectively). CONCLUSIONS Current and past exposure to ADT is linked to higher risk of falls and frailty than no treatment. PCSs should be appropriately counseled on fall prevention strategies, and approaches to reduce frailty should be considered.
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Affiliation(s)
- Kerri M Winters-Stone
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon.,School of Nursing, Oregon Health & Science University, Portland, Oregon
| | - Esther Moe
- Department of Medicine, Oregon Health & Science University, Portland, Oregon
| | - Julie N Graff
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
| | | | - Sydnee Stoyles
- School of Nursing, Oregon Health & Science University, Portland, Oregon
| | - Carolyn Borsch
- School of Nursing, Oregon Health & Science University, Portland, Oregon
| | - Joshi J Alumkal
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
| | | | - Tomasz M Beer
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
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Ramalingam S, Ramamurthy VP, Njar VCO. Dissecting major signaling pathways in prostate cancer development and progression: Mechanisms and novel therapeutic targets. J Steroid Biochem Mol Biol 2017; 166:16-27. [PMID: 27481707 PMCID: PMC7371258 DOI: 10.1016/j.jsbmb.2016.07.006] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2016] [Revised: 07/08/2016] [Accepted: 07/12/2016] [Indexed: 12/19/2022]
Abstract
Prostate cancer (PCa) is the most frequently diagnosed non-cutaneous malignancy and leading cause of cancer mortality in men. At the initial stages, prostate cancer is dependent upon androgens for their growth and hence effectively combated by androgen deprivation therapy (ADT). However, most patients eventually recur with an androgen deprivation-resistant phenotype, referred to as castration-resistant prostate cancer (CRPC), a more aggressive form for which there is no effective therapy presently available. The current review is an attempt to cover and establish an understanding of some major signaling pathways implicated in prostate cancer development and castration-resistance, besides addressing therapeutic strategies that targets the key signaling mechanisms.
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Affiliation(s)
- Senthilmurugan Ramalingam
- Department of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA; Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA
| | - Vidya P Ramamurthy
- Department of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA; Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA
| | - Vincent C O Njar
- Department of Pharmacology, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA; Center for Biomolecular Therapeutics, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, 685 West Baltimore Street, Baltimore, MD 21201-1559, USA.
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13
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Hotte SJ. Addressing taxane resistance in metastatic castration-resistant prostate cancer: a focus on chaperone proteins. Future Oncol 2017; 13:369-379. [DOI: 10.2217/fon-2016-0279] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Despite the significant survival benefit of taxane therapy in metastatic castration-resistant prostate cancer (mCRPC), all patients inevitably develop treatment resistance. An understanding of resistance mechanisms has led to new therapies for prostate cancer (cabazitaxel, abiraterone and enzalutamide), all of which have improved survival following first-line docetaxel. Another treatment, currently in development, targets the prosurvival molecule clusterin. Custirsen, an antisense molecule that inhibits clusterin production, has shown promise in combination with docetaxel in mCRPC patients at risk for poor outcomes. Although optimal sequence and combination of available therapies is unclear, the heterogeneity of mCRPC suggests a continuing need for personalized treatment regimens and improved abilities to predict which patients will respond to the available treatment options.
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Affiliation(s)
- Sebastien J Hotte
- Department of Oncology, Division of Medical Oncology, Juravinski Cancer Centre, 699 Concession Street, Hamilton, Ontario, L8V 5C2, Canada
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14
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Kongsted P, Svane IM, Lindberg H, Sengeløv L. Clinical Impact of the Number of Treatment Cycles in First-Line Docetaxel for Patients With Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer 2016; 15:e281-e287. [PMID: 27692811 DOI: 10.1016/j.clgc.2016.08.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/12/2016] [Accepted: 08/26/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND We investigated the impact of the number of docetaxel cycles administered in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line chemotherapy. PATIENTS AND METHODS Charts from 421 consecutive patients who initiated standard treatment with docetaxel-based chemotherapy (75 mg/m2 every 3 weeks) between 2007 and 2013 were reviewed. Patients who received < 6 cycles of docetaxel were excluded from the analysis. Remaining patients were divided into 2 groups on the basis of whether or not ≥ 9 cycles of docetaxel were administered (n = 108 and 184, respectively). Reasons for treatment discontinuation and postdocetaxel treatments were registered. Prostate-specific antigen (PSA) responses were defined as a confirmed ≥ 50% decrease in baseline PSA levels. Overall survival (OS) was calculated from start of therapy using the Kaplan-Meier method. Cox proportional hazards were calculated to estimate the effect of clinical variables on OS. RESULTS OS was longer in patients treated with ≥ 9 cycles of docetaxel (21.9 months vs. 17.2 months; P < .0001, log rank). Survival also favored patients treated with ≥ 9 cycles of docetaxel when only patients ending docetaxel because of toxicity or treatment conclusion (22.3 vs. 19.4 months; P = .048, log rank) or patients who achieved a PSA response (22.3 vs. 18.7 months; P = .012, log rank) were evaluated. mCRPC-related prognostic factors and patients who received ≥ 1 subsequent line of therapy post-docetaxel were well balanced. CONCLUSION On the basis of our retrospective findings, a superior OS was found in patients treated with ≥ 9 cycles of docetaxel when adjusting for known prognostic factors. Dose reductions might increase the number of docetaxel cycles administered.
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Affiliation(s)
- Per Kongsted
- Department of Oncology, Herlev University Hospital, Herlev, Denmark.
| | - Inge Marie Svane
- Department of Oncology, Herlev University Hospital, Herlev, Denmark
| | | | - Lisa Sengeløv
- Department of Oncology, Herlev University Hospital, Herlev, Denmark
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Hsiao JJ, Smits MM, Ng BH, Lee J, Wright ME. Discovery Proteomics Identifies a Molecular Link between the Coatomer Protein Complex I and Androgen Receptor-dependent Transcription. J Biol Chem 2016; 291:18818-42. [PMID: 27365400 PMCID: PMC5009256 DOI: 10.1074/jbc.m116.732313] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2016] [Indexed: 12/18/2022] Open
Abstract
Aberrant androgen receptor (AR)-dependent transcription is a hallmark of human prostate cancers. At the molecular level, ligand-mediated AR activation is coordinated through spatial and temporal protein-protein interactions involving AR-interacting proteins, which we designate the “AR-interactome.” Despite many years of research, the ligand-sensitive protein complexes involved in ligand-mediated AR activation in prostate tumor cells have not been clearly defined. Here, we describe the development, characterization, and utilization of a novel human LNCaP prostate tumor cell line, N-AR, which stably expresses wild-type AR tagged at its N terminus with the streptavidin-binding peptide epitope (streptavidin-binding peptide-tagged wild-type androgen receptor; SBP-AR). A bioanalytical workflow involving streptavidin chromatography and label-free quantitative mass spectrometry was used to identify SBP-AR and associated ligand-sensitive cytosolic proteins/protein complexes linked to AR activation in prostate tumor cells. Functional studies verified that ligand-sensitive proteins identified in the proteomic screen encoded modulators of AR-mediated transcription, suggesting that these novel proteins were putative SBP-AR-interacting proteins in N-AR cells. This was supported by biochemical associations between recombinant SBP-AR and the ligand-sensitive coatomer protein complex I (COPI) retrograde trafficking complex in vitro. Extensive biochemical and molecular experiments showed that the COPI retrograde complex regulates ligand-mediated AR transcriptional activation, which correlated with the mobilization of the Golgi-localized ARA160 coactivator to the nuclear compartment of prostate tumor cells. Collectively, this study provides a bioanalytical strategy to validate the AR-interactome and define novel AR-interacting proteins involved in ligand-mediated AR activation in prostate tumor cells. Moreover, we describe a cellular system to study how compartment-specific AR-interacting proteins influence AR activation and contribute to aberrant AR-dependent transcription that underlies the majority of human prostate cancers.
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Affiliation(s)
- Jordy J Hsiao
- From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa City, Iowa 52242
| | - Melinda M Smits
- From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa City, Iowa 52242
| | - Brandon H Ng
- From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa City, Iowa 52242
| | - Jinhee Lee
- From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa City, Iowa 52242
| | - Michael E Wright
- From the Department of Molecular Physiology and Biophysics, Carver College of Medicine, Iowa City, Iowa 52242
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Yang Y, Bai W, Chen Y, Nan S, Lin Y, Ying T, Hu B. Low-frequency ultrasound-mediated microvessel disruption combined with docetaxel to treat prostate carcinoma xenografts in nude mice: A novel type of chemoembolization. Oncol Lett 2016; 12:1011-1018. [PMID: 27446386 DOI: 10.3892/ol.2016.4703] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2015] [Accepted: 05/06/2016] [Indexed: 01/16/2023] Open
Abstract
The aim of the present study was to investigate whether low-frequency ultrasound (US)-mediated microvessel disruption combined with docetaxel (DTX) can be used as a novel type of chemoembolization. Mice were assigned to four groups: i) The USMB group, treated with low-frequency US combined with microbubbles (USMB); ii) the DTX group, treated with DTX; iii) the USMB + DTX group, treated with combined therapy; and iv) the control group, which was untreated. Immediately after the first treatment, the average peak intensity (API) on contrast-enhanced US was calculated, and tumors were excised for hematoxylin and eosin (HE) staining. At 2 weeks post-treatment, the tumor volumes and wet weights were calculated, and tumors were excised for immunohistochemistry to calculate apoptotic index (AI), proliferative index (PI) and microvessel density (MVD) values. Immediately after the first treatment, in the DTX and control groups, the tumors demonstrated abundant perfusion enhancement, while in the USMB + DTX and USMB groups, blood perfusion of the tumors was interrupted. Compared with that of the control group, the API was significantly lower in the USMB + DTX USMB groups (all P<0.001). HE staining showed that tumor microvasculature was disrupted into flaky hematomas and severely dilated microvessels in the USMB + DTX and USMB groups. In the DTX and control groups, there was no distinct evidence of the disruption and dilation of blood microvessels. At the end of the treatment, the mean tumor inhibition ratio was 73.33, 46.67 and 33.33% for the USMB + DTX, DTX and USMB groups, respectively. The USMB + DTX group had the highest AI, and the lowest PI and MVD compared with the other groups, although the difference between the USMB + DTX and DTX groups with regard to PI and MVD was not significant (USMB + DTX vs. DTX group, P=0.345 and P=0.059, respectively). In conclusion, as a novel type of chemoembolization, USMB combined with DTX is more effective than USMB or DTX alone in inhibiting tumor growth via the enhancement of apoptosis, and the suppression of proliferation and angiogenesis.
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Affiliation(s)
- Yu Yang
- Department of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China
| | - Wenkun Bai
- Department of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China
| | - Yini Chen
- Department of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China
| | - Shuliang Nan
- Department of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China
| | - Yanduan Lin
- Department of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China
| | - Tao Ying
- Department of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China
| | - Bing Hu
- Department of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai Institute of Ultrasound in Medicine, Shanghai 200233, P.R. China
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Moriceau G, Guillot A, Pacaut C, Méry B, Falk AT, Trone JC, Collard O, De Laroche G, Fournel P, Merrouche Y, Magné N. Translating Clinical Evidence-Based Medicine into the Real World: Single-Center Experience with Cabazitaxel in Metastatic Prostate Cancer Patients. Chemotherapy 2016; 61:127-33. [DOI: 10.1159/000441379] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Accepted: 09/28/2015] [Indexed: 11/19/2022]
Abstract
Background: We studied the efficacy and safety of cabazitaxel in unselected real-life patients. Patients and Methods: We retrospectively investigated all patients with metastatic prostate cancer (mPC) treated with cabazitaxel 25 mg/m2 i.v. every 3 weeks combined with oral prednisolone (10 mg once daily) after first-line docetaxel chemotherapy. Study issues were to report patient characteristics and cabazitaxel data in terms of tolerance and efficacy. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method. All data were compared with TROPIC results. Results: From 2011 to 2014, 41 patients received cabazitaxel; 15 patients (37%) had a performance status (PS) ≥2 versus 7% (p < 0.0001) in TROPIC, and 38 patients (93%) presented a Gleason score ≥7 at baseline (vs. 60%; p < 0.0001). All patients had metastatic disease at baseline. Previous therapies were radiotherapy in 17 patients (41 vs. 61%; p = 0.01) and surgery in 24 patients (59 vs. 52%; p = 0.4). The median number of cabazitaxel cycles was 5 (1-10) versus 6 (3-10) in TROPIC. Five patients completed 10 cycles of cabazitaxel (12%) versus 28% in TROPIC (p = 0.03). Toxicities were anemia (12 patients, 29%), diarrhea (9 patients, 22%), nausea (7 patients, 17%), pain (6 patients, 15%), sepsis (4 patients, 10%), neutropenia (3 patients, 7%) and urinary tract infection (1 patient, 2%). The tumor response rate was 19.5 versus 14.4% in TROPIC (nonsignificant). PFS was 4.5 months (95% CI 3.3-6.4) in our analysis and 2.8 months (95% CI 2.4-3.0) in TROPIC. OS was 12.1 months (95% CI 9.2 to not reached) and 15.1 months (95% CI 14.1-16.3), respectively. Conclusion: In our unselected mPC patients with poorer baseline clinical conditions and aggressive disease, cabazitaxel seems efficient and not more toxic than in the TROPIC study.
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18
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Massari F, Modena A, Ciccarese C, Pilotto S, Maines F, Bracarda S, Sperduti I, Giannarelli D, Carlini P, Santini D, Tortora G, Porta C, Bria E. Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials. Crit Rev Oncol Hematol 2015; 98:254-63. [PMID: 26638863 DOI: 10.1016/j.critrevonc.2015.11.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Revised: 09/25/2015] [Accepted: 11/12/2015] [Indexed: 11/28/2022] Open
Abstract
We performed a sensitivity analysis, cumulating all randomized clinical trials (RCTs) in which patients with metastatic castration-resistant prostate cancer (mCRPC) received systemic therapy, to evaluate if the comparison of RCTs may drive to biased survival estimations. An overall survival (OS) significant difference according to therapeutic strategy was more likely be determined in RCTs evaluating hormonal drugs versus those studies testing immunotherapy, chemotherapy or other strategies. With regard to control arm, an OS significant effect was found for placebo-controlled trials versus studies comparing experimental treatment with active therapies. Finally, regarding to docetaxel (DOC) timing, the OS benefit was more likely to be proved in Post-DOC setting in comparison with DOC and Pre-DOC. These data suggest that clinical trial design should take into account new benchmarks such as the type of treatment strategy, the choice of the comparator and the phase of the disease in relation to the administration of standard chemotherapy.
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Affiliation(s)
- Francesco Massari
- Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
| | - Alessandra Modena
- Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
| | - Chiara Ciccarese
- Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
| | - Sara Pilotto
- Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
| | | | - Sergio Bracarda
- Medical Oncology, Ospedale San Donato, Istituto Toscano Tumori, Arezzo, Italy.
| | | | | | - Paolo Carlini
- Medical Oncology, Regina Elena National Cancer Institute, Roma, Italy.
| | - Daniele Santini
- Medical Oncology, Policlinico Universitario Campus Bio-Medico, Roma, Italy.
| | - Giampaolo Tortora
- Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
| | - Camillo Porta
- Medical Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
| | - Emilio Bria
- Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy.
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Yang KF, Lee HY, Wu WJ, Huang CH, Chou YH, Huang CN, Lee YC, Huang SP. Prediction for survival following docetaxel-based chemotherapy in Taiwanese men with castration-resistant metastatic prostate cancer. UROLOGICAL SCIENCE 2015. [DOI: 10.1016/j.urols.2015.03.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
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Abstract
This review is to describe synergistic effects of various combinations of dietary natural products including curcumin, quercetin, soybean isoflavones, silibinin, and EGCG that have potential for the treatment of prostate cancer. These data can provide valuable insights into the future rational design and development of synergistic and/or hybrid agents for potential treatment of prostate cancer.
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22
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Gee A, Challapalli A, Bahl A. Health-related quality of life in men with metastatic castration–resistant prostate cancer. Expert Rev Pharmacoecon Outcomes Res 2015; 15:941-9. [DOI: 10.1586/14737167.2015.1107479] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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Shameem R, Hamid MS, Xu KY, Wu S. Comparative analysis of the effectiveness of abiraterone before and after docetaxel in patients with metastatic castration-resistant prostate cancer. World J Clin Oncol 2015; 6:64-72. [PMID: 26266103 PMCID: PMC4530380 DOI: 10.5306/wjco.v6.i4.64] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2014] [Revised: 05/13/2015] [Accepted: 06/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.
METHODS: The databases including PubMed and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer (CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity.
RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before (n = 1088) and after chemotherapy (n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival (P = 0.92) and prostate-specific antigen (PSA) progression-free survival (P = 0.13), but reduced its effect on radiographic-progression-free survival (P = 0.04), objective response rate (P < 0.001), and PSA response rate (P < 0.001). Prior chemotherapy significantly increased the specific risk of fluid retention and edema (P < 0.001) and hypokalemia (P < 0.001), but decreased the risk of all-grade hypertension (P < 0.001) attributable to abiraterone. There was no significant difference of cardiac disorders associated with abiraterone between the two settings (P = 0.58).
CONCLUSION: Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC.
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Zhou F, Chen X, Fan S, Tai S, Jiang C, Zhang Y, Hao Z, Zhou J, Shi H, Zhang L, Liang C. GSK1838705A, an insulin-like growth factor-1 receptor/insulin receptor inhibitor, induces apoptosis and reduces viability of docetaxel-resistant prostate cancer cells both in vitro and in vivo. Onco Targets Ther 2015; 8:753-60. [PMID: 25926740 PMCID: PMC4403692 DOI: 10.2147/ott.s79105] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Prostate cancer is the leading malignancy and the second most common cause of cancer-related death in men. Despite high cure rates with surgery and/or radiation, 30%-40% of patients eventually develop advanced cancer. Docetaxel is one of the most effective and well established chemotherapeutic agents for prostate cancer. However, docetaxel resistance often develops within months. Combination therapies have been proposed to improve the therapeutic efficacy of docetaxel in prostate cancer, and there is an urgent need to identify agents that are effective for treatment of the disease, especially docetaxel-resistant prostate cancer. In this work, we investigated the activity of GSK1838705A, a potent insulin-like growth factor-1 receptor (IGF1R)/insulin receptor (IR) inhibitor, in prostate cancer, especially docetaxel-resistant prostate cancer. We found that GSK1838705A could effectively reduce the viability of both docetaxel-sensitive and docetaxel-resistant prostate cancer cells. GSK1838705A induced marked apoptosis in docetaxel-resistant cells, and also dramatically inhibited migration of these cells. Further, GSK1838705A significantly inhibited phosphorylation of IGF1R/IR. Importantly, GSK1838705A significantly suppressed docetaxel-resistant PC-3R tumor growth in vivo. This is the first study of GSK1838705A in prostate cancer. Our results indicate that GSK1838705A is a promising compound for the treatment of prostate cancer, especially for those who develop resistance to docetaxel, and might shed new light on treatment for prostate cancer.
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Affiliation(s)
- Fayou Zhou
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China ; Department of Urology, Traditional Chinese Medical Hospital of Wuhu City, WuHu, People's Republic of China
| | - Xianguo Chen
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Song Fan
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Sheng Tai
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Changqin Jiang
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Yifei Zhang
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Zongyao Hao
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Jun Zhou
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Haoqiang Shi
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Li Zhang
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
| | - Chaozhao Liang
- Department of Urology, First Affiliated Hospital of Anhui Medical University, Hefei, People's Republic of China
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Houédé N, Beuzeboc P, Gourgou S, Tosi D, Moise L, Gravis G, Delva R, Fléchon A, Latorzeff I, Ferrero JM, Oudard S, Tartas S, Laguerre B, Topart D, Roubaud G, Agherbi H, Rebillard X, Azria D. Abiraterone acetate in patients with metastatic castration-resistant prostate cancer: long term outcome of the Temporary Authorization for Use programme in France. BMC Cancer 2015; 15:222. [PMID: 25884302 PMCID: PMC4392747 DOI: 10.1186/s12885-015-1257-2] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Accepted: 03/25/2015] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND COU-AA-301 trial has proved that abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improved overall survival (OS) of patients with metastatic castration resistant prostate cancer (mCRPC) after a first line of docetaxel. Based on this result, a Temporary Authorization for Use (TAU) was performed between December 2010 and July 2011 to provide patients with mCRPC the opportunity to receive AA before its commercialization. The aim of this study was to evaluate safety and efficacy of AA treatment in this TAU. METHODS Between December 2010 and July 2011, we conducted an ambispective, multicentric cohort study and investigated data from 20 centres participating to the AA TAU for patients presenting mCRPC and already treated by a first line of chemotherapy (CT). Statistical analyses of the data were performed using the Stata software v13 to identify predictive and prognostic factors. RESULTS Among the 408 patients, 306 were eligible with a follow-up at 3 years. Median OS was 37.1 months from beginning of CT and 14.6 months from AA introduction. 211 patients (69%) received ≥ 3 months of AA and 95 patients (31%) were treated less than 3 months. In the multivariate analyses, duration of AA was significantly correlated with PSA decrease at 3 months. Additionally, shorter time under AA treatment, presence of multiple sites of metastasis and previous hormonal treatment duration were three independent factors associated with poorer OS. At the time of analysis ten patients were still under treatment for more than 3 years. CONCLUSIONS Biochemical response monitored by PSA changes at 3 months is a strong predictive factor for AA treatment duration. Some high responders' patients could beneficiate from AA for more than 3 years.
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Affiliation(s)
- Nadine Houédé
- Department of Medical Oncology, Nîmes University Hospital, Nîmes, France. .,INSERM U1194, Montpellier, France.
| | | | - Sophie Gourgou
- Biostatistics Unit, ICM - Montpellier Cancer Institute, Montpellier, France.
| | - Diego Tosi
- Department of Medical Oncology, ICM - Montpellier Cancer Institute, Montpellier, France.
| | - Laura Moise
- Department of Medical Oncology, François Baclesse Cancer Centre, Caen, France.
| | - Gwenaëlle Gravis
- Department of Medical Oncology, Paoli Calmette Institute, Marseille, France.
| | - Remy Delva
- Department of Medical Oncology, Paul Papin Cancer Centre, Angers, France.
| | - Aude Fléchon
- Department of Medical Oncology, Leon Bérard Cancer Centre, Lyon, France.
| | | | - Jean-Marc Ferrero
- Department of Medical Oncology, Antoine Lacassagne Cancer Centre, Nice, France.
| | - Stéphane Oudard
- Department of Medical Oncology, Georges Pompidou European Hospital, Paris, France.
| | - Sophie Tartas
- Department of Medical Oncology, Lyon University Hospital, Lyon, France.
| | - Brigitte Laguerre
- Department of Medical Oncology, Eugène Marquis Cancer Centre, Rennes, France.
| | - Delphine Topart
- Department of Medical Oncology, Montpellier University Hospital, Montpellier, France.
| | - Guilhem Roubaud
- Department of Medical Oncology, Bergonié Cancer Institute, Bordeaux, France.
| | | | - Xavier Rebillard
- Department of Urology, Clinique Beausoleil, Montpellier, France.
| | - David Azria
- INSERM U1194, Montpellier, France. .,Department of Radiation Oncology, ICM - Montpellier Cancer Institute, Montpellier, France.
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Shen Y, Ma Z, Chen F, Dong Q, Hu Q, Bai L, Chen J. Effective photothermal chemotherapy with docetaxel-loaded gold nanospheres in advanced prostate cancer. J Drug Target 2015; 23:568-76. [DOI: 10.3109/1061186x.2015.1018910] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
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Joly F, Delva R, Mourey L, Sevin E, Bompas E, Vedrine L, Ravaud A, Eymard JC, Tubiana-Mathieu N, Linassier C, Houede N, Guillot A, Ringensen F, Cojocarasu O, Valenza B, Leconte A, Lheureux S, Clarisse B, Oudard S. Clinical benefits of non-taxane chemotherapies in unselected patients with symptomatic metastatic castration-resistant prostate cancer after docetaxel: the GETUG-P02 study. BJU Int 2014; 115:65-73. [DOI: 10.1111/bju.12552] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Florence Joly
- Medical Oncology-Clinical Research Department; Centre François Baclesse - CHU Côte de Nacre; Caen France
- Universite Basse Normandie; Caen France
| | - Remy Delva
- Medical Oncology; Institut de Cancérologie de l'Ouest Centre Paul Papin; Angers France
| | - Loïc Mourey
- Medical Oncology; Institut Claudius Régaud; Toulouse France
| | - Emmanuel Sevin
- Medical Oncology-Clinical Research Department; Centre François Baclesse - CHU Côte de Nacre; Caen France
| | | | | | - Alain Ravaud
- Medical Oncology; Hôpital Saint-André; Bordeaux France
| | | | | | | | - Nadine Houede
- Medical Oncology; Institut Bergonié; Bordeaux France
| | - Aline Guillot
- Institut de Cancérologie de la Loire; Saint-Etienne France
| | | | | | - Bruno Valenza
- Oncology-Hematology; Centre Hospitalier; Frejus France
| | | | - Stéphanie Lheureux
- Medical Oncology-Clinical Research Department; Centre François Baclesse - CHU Côte de Nacre; Caen France
| | | | - Stéphane Oudard
- Medical Oncology Department; Georges Pompidou Hospital; Paris France
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Bracarda S, Sisani M, Marrocolo F, Hamzaj A, Del Buono S, Altavilla A. Clinical implications for a treatment algorithm and differential indication to hormone therapy and chemotherapy options in metastatic castrate-resistant prostate cancer: a personal view. Expert Rev Anticancer Ther 2014; 14:1283-94. [DOI: 10.1586/14737140.2014.965686] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Winters-Stone KM, Beer TM. Review of Exercise Studies in Prostate Cancer Survivors Receiving Androgen Deprivation Therapy Calls for an Aggressive Research Agenda to Generate High-Quality Evidence and Guidance for Exercise As Standard of Care. J Clin Oncol 2014; 32:2518-9. [DOI: 10.1200/jco.2014.55.8189] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Affiliation(s)
- Kerri M. Winters-Stone
- Knight Cancer Institute, School of Nursing, Oregon Health and Science University, Portland, OR
| | - Tomasz M. Beer
- Knight Cancer Institute, School of Medicine, Oregon Health and Science University, Portland, OR
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Azarenko O, Smiyun G, Mah J, Wilson L, Jordan MA. Antiproliferative mechanism of action of the novel taxane cabazitaxel as compared with the parent compound docetaxel in MCF7 breast cancer cells. Mol Cancer Ther 2014; 13:2092-103. [PMID: 24980947 DOI: 10.1158/1535-7163.mct-14-0265] [Citation(s) in RCA: 66] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Cabazitaxel, a novel chemotherapeutic taxane, is effective against docetaxel-resistant cells and tumors. It is approved for treatment of metastatic hormone-refractory prostate cancer in patients pretreated with docetaxel. Objective responses have been observed in many other cancers, including pretreated metastatic breast cancer. Cabazitaxel and docetaxel share a high degree of structural similarity. The basis for cabazitaxel's efficacy is unclear, and its mechanism has not been described. We compared the effects of cabazitaxel and docetaxel on MCF7 human breast cancer cells expressing fluorescent tubulin. Both drugs inhibited cell proliferation (IC50s, cabazitaxel, 0.4 ± 0.1 nmol/L, docetaxel, 2.5 ± 0.5 nmol/L) and arrested cells in metaphase by inducing mitotic spindle abnormalities. Drug concentrations required for half-maximal mitotic arrest at 24 hours were similar (1.9 nmol/L cabazitaxel and 2.2 nmol/L docetaxel). Cabazitaxel suppressed microtubule dynamic instability significantly more potently than docetaxel. In particular, cabazitaxel (2 nmol/L) suppressed the microtubule shortening rate by 59% (compared with 49% for 2 nmol/L docetaxel), the growing rate by 33% (vs. 19%), and overall dynamicity by 83% (vs. 64%). Cabazitaxel was taken up into cells significantly faster than docetaxel, attaining an intracellular concentration of 25 μmol/L within 1 hour, compared with 10 hours for docetaxel. Importantly, after washing, the intracellular cabazitaxel concentration remained high, whereas the docetaxel concentration was significantly reduced. The data indicate that the potency of cabazitaxel in docetaxel-resistant tumors is due to stronger suppression of microtubule dynamics, faster drug uptake, and better intracellular retention than occurs with docetaxel.
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Affiliation(s)
- Olga Azarenko
- Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California
| | - Gregoriy Smiyun
- Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California
| | - Jeffrey Mah
- Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California
| | - Leslie Wilson
- Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California
| | - Mary Ann Jordan
- Department of Molecular, Cellular, and Developmental Biology and the Neuroscience Research Institute, University of California Santa Barbara, Santa Barbara, California
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Krahn MD, Bremner KE, Luo J, Alibhai SMH. Health care costs for prostate cancer patients receiving androgen deprivation therapy: treatment and adverse events. ACTA ACUST UNITED AC 2014; 21:e457-65. [PMID: 24940106 DOI: 10.3747/co.21.1865] [Citation(s) in RCA: 60] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Serious adverse events have been associated with androgen deprivation therapy (adt) for prostate cancer (pca), but few studies address the costs of those events. METHODS All pca patients (ICD-9-CM 185) in Ontario who started 90 days or more of adt or had orchiectomy at the age of 66 or older during 1995-2005 (n = 26,809) were identified using the Ontario Cancer Registry and drug and hospital data. Diagnosis dates of adverse events-myocardial infarction, acute coronary syndrome, congestive heart failure, stroke, deep vein thrombosis or pulmonary embolism, any diabetes, and fracture or osteoporosis-before and after adt initiation were determined from administrative data. We excluded patients with the same diagnosis before and after adt, and we allocated each patient's time from adt initiation to death or December 31, 2007, into health states: adt (no adverse event), adt-ae (specified single adverse event), Multiple (>1 event), and Final (≤180 days before death). We used methods for Canadian health administrative data to estimate annual total health care costs during each state, and we examined monthly trends. RESULTS Approximately 50% of 21,811 patients with no pre-adt adverse event developed 1 or more events after adt. The costliest adverse event state was stroke ($26,432/year). Multiple was the most frequent (n = 2,336) and the second most costly health state ($24,374/year). Costs were highest in the first month after diagnosis (from $1,714 for diabetes to $14,068 for myocardial infarction). Costs declined within 18 months, ranging from $784 per 30 days (diabetes) to $1,852 per 30 days (stroke). Adverse events increased the costs of adt by 100% to 265%. CONCLUSIONS The economic burden of adverse events is relevant to programs and policies from clinic to government, and that burden merits consideration in the risks and benefits of adt.
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Affiliation(s)
- M D Krahn
- Toronto General Research Institute, Toronto General Hospital, Toronto, ON. ; Department of Medicine, Toronto General Hospital, Toronto, ON. ; Faculty of Pharmacy, University of Toronto, Toronto, ON. ; Department of Medicine, University of Toronto, Toronto, ON. ; Toronto Health Economics and Technology Assessment Collaborative, Toronto, ON. ; Institute for Clinical Evaluative Sciences, Toronto, ON
| | - K E Bremner
- Toronto General Research Institute, Toronto General Hospital, Toronto, ON. ; Toronto Health Economics and Technology Assessment Collaborative, Toronto, ON
| | - J Luo
- Institute for Clinical Evaluative Sciences, Toronto, ON
| | - S M H Alibhai
- Toronto General Research Institute, Toronto General Hospital, Toronto, ON. ; Department of Medicine, Toronto General Hospital, Toronto, ON. ; Toronto Health Economics and Technology Assessment Collaborative, Toronto, ON
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Ganju A, Yallapu MM, Khan S, Behrman SW, Chauhan SC, Jaggi M. Nanoways to overcome docetaxel resistance in prostate cancer. Drug Resist Updat 2014; 17:13-23. [PMID: 24853766 DOI: 10.1016/j.drup.2014.04.001] [Citation(s) in RCA: 75] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2014] [Revised: 03/17/2014] [Accepted: 03/22/2014] [Indexed: 12/18/2022]
Abstract
Prostate cancer is the most common non-cutaneous malignancy in American men. Docetaxel is a useful chemotherapeutic agent for prostate cancer that has been available for over a decade, but the length of the treatment and systemic side effects hamper compliance. Additionally, docetaxel resistance invariably emerges, leading to disease relapse. Docetaxel resistance is either intrinsic or acquired by adopting various mechanisms that are highly associated with genetic alterations, decreased influx and increased efflux of drugs. Several combination therapies and small P-glycoprotein inhibitors have been proposed to improve the therapeutic potential of docetaxel in prostate cancer. Novel therapeutic strategies that may allow reversal of docetaxel resistance include alterations of enzymes, improving drug uptake and enhancement of apoptosis. In this review, we provide the most current docetaxel reversal approaches utilizing nanotechnology. Nanotechnology mediated docetaxel delivery is superior to existing therapeutic strategies and a more effective method to induce P-glycoprotein inhibition, enhance cellular uptake, maintain sustained drug release, and improve bioavailability.
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Affiliation(s)
- Aditya Ganju
- Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA; College of Graduate Health Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Murali M Yallapu
- Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
| | - Sheema Khan
- Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Stephen W Behrman
- Department of Surgery, University of Tennessee Health Science Center, Memphis, TN 38163, USA
| | - Subhash C Chauhan
- Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
| | - Meena Jaggi
- Department of Pharmaceutical Sciences and the Center for Cancer Research, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
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Di Lorenzo G, Bracarda S, Buonerba C, Aieta M, Mirone V. Poor survival in prostate cancer patients with primary refractoriness to docetaxel. Eur Urol 2013; 65:505-7. [PMID: 24211139 DOI: 10.1016/j.eururo.2013.10.037] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2013] [Accepted: 10/21/2013] [Indexed: 11/30/2022]
Affiliation(s)
- Giuseppe Di Lorenzo
- Genitourinary Cancer Section, Medical Oncology Division, Department of Clinical and Experimental Medicine, University Federico II, Naples, Italy.
| | | | - Carlo Buonerba
- Genitourinary Cancer Section, Medical Oncology Division, Department of Clinical and Experimental Medicine, University Federico II, Naples, Italy
| | - Michele Aieta
- UO Oncologia, Ospedale Oncologico Regionale, Rionero in Vulture, Potenza, Italy
| | - Vincenzo Mirone
- Department of Urology, University Federico II, Naples, Italy
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