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Sample records for advanced metastatic prostate

  1. Evolving treatment paradigms for locally advanced and metastatic prostate cancer.

    Science.gov (United States)

    Dorff, Tanya B; Quek, Marcus L; Daneshmand, Siamak; Pinski, Jacek

    2006-11-01

    While men with early stage prostate cancer typically enjoy long-term survival after definitive management, for those who present with locally advanced or metastatic disease, survival is compromised. Multimodality therapy can prolong survival in these patients, with state-of-the-art options including intensity-modulated radiation or brachytherapy in conjunction with androgen ablation, adjuvant androgen ablation and/or chemotherapy with radical retropubic prostatectomy. In addition, novel biological therapies are being explored to target the unique molecular changes in prostate cancer cells and their interactions with the microenvironment. With these advances the outlook will undoubtedly improve, even for patients presenting with advanced disease. Careful application of these emerging therapies to a select group of prostate cancer patients most likely to obtain benefit from them is the challenge for urologists, medical oncologists and radiation oncologists for the future.

  2. A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Tyrrell, C J; Kaisary, A V; Iversen, P;

    1998-01-01

    To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer.......To evaluate the efficacy and tolerability of 'Casodex' monotherapy (150 mg daily) for metastatic and locally advanced prostate cancer....

  3. Evaluation of urinary prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG score changes when starting androgen-deprivation therapy with triptorelin 6-month formulation in patients with locally advanced and metastatic prostate cancer

    NARCIS (Netherlands)

    Martinez-Pineiro, L.; Schalken, J.A.; Cabri, P.; Maisonobe, P.; Taille, A. De La; Study, G.

    2014-01-01

    OBJECTIVE: To assess prostate cancer antigen-3 (PCA3) and TMPRSS2-ERG scores in patients with advanced and metastatic prostate cancer at baseline and after 6 months of treatment with triptorelin 22.5 mg, and analyse these scores in patient-groups defined by different disease characteristics. PATIENT

  4. {sup 89}Zr-huJ591 immuno-PET imaging in patients with advanced metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Pandit-Taskar, Neeta; Solomon, Stephen B.; Durack, Jeremy C.; Carrasquillo, Jorge A.; Lefkowitz, Robert A.; Osborne, Joseph R. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); O' Donoghue, Joseph A. [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Beylergil, Volkan; Ruan, Shutian; Cheal, Sarah M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Lyashchenko, Serge [Memorial Sloan Kettering Cancer Center, Department of Radiochemistry and Molecular Imaging Probes Core, New York, NY (United States); Gonen, Mithat [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Lewis, Jason S. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Radiochemistry and Molecular Imaging Probes Core, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Holland, Jason P. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Harvard Medical School, Department of Radiology of Massachusetts General Hospital, Boston, MA (United States); Reuter, Victor E. [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Weill Cornell Medical College, Department of Pathology, New York, NY (United States); Loda, Massimo F. [Dana-Farber Cancer Institute, Boston, MA (United States); Broad Institute of Harvard and MIT, Cambridge, MA (United States); Smith-Jones, Peter M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Department of Psychiatry and Behavioral Science of Stony Brook University, Stony Brook, NY (United States); Weber, Wolfgang A.; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Program in Molecular Pharmacology and Chemistry, New York, NY (United States); Weill Cornell Medical College, Department of Radiology, New York, NY (United States); Bander, Neil H. [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States); Weill Cornell Medical College, Department of Urology, New York, NY (United States); Scher, Howard I.; Morris, Michael J. [Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY (United States); Weill Cornell Medical College, Department of Medicine, New York, NY (United States)

    2014-11-15

    Given the bone tropism of prostate cancer, conventional imaging modalities poorly identify or quantify metastatic disease. {sup 89}Zr-huJ591 positron emission tomography (PET) imaging was performed in patients with metastatic prostate cancer to analyze and validate this as an imaging biomarker for metastatic disease. The purpose of this initial study was to assess safety, biodistribution, normal organ dosimetry, and optimal imaging time post-injection for lesion detection. Ten patients with metastatic prostate cancer received 5 mCi of {sup 89}Zr-huJ591. Four whole-body scans with multiple whole-body count rate measurements and serum activity concentration measurements were obtained in all patients. Biodistribution, clearance, and lesion uptake by {sup 89}Zr-huJ591 immuno-PET imaging was analyzed and dosimetry was estimated using MIRD techniques. Initial assessment of lesion targeting of {sup 89}Zr-huJ591 was done. Optimal time for imaging post-injection was determined. The dose was well tolerated with mild chills and rigors seen in two patients. The clearance of {sup 89}Zr-huJ591 from serum was bi-exponential with biological half-lives of 7 ± 4.5 h (range 1.1-14 h) and 62 ± 13 h (range 51-89 h) for initial rapid and later slow phase. Whole-body biological clearance was 219 ± 48 h (range 153-317 h). The mean whole-body and liver residence time was 78.7 and 25.6 h, respectively. Dosimetric estimates to critical organs included liver 7.7 ± 1.5 cGy/mCi, renal cortex 3.5 ± 0.4 cGy/mCi, and bone marrow 1.2 ± 0.2 cGy/mCi. Optimal time for patient imaging after injection was 7 ± 1 days. Lesion targeting of bone or soft tissue was seen in all patients. Biopsies were performed in 8 patients for a total 12 lesions, all of which were histologically confirmed as metastatic prostate cancer. One biopsy-proven lesion was not positive on {sup 89}Zr-huJ591, while the remaining 11 lesions were {sup 89}Zr-huJ591 positive. Two biopsy-positive nodal lesions were noted only on

  5. Repurposing Itraconazole as a Treatment for Advanced Prostate Cancer: A Noncomparative Randomized Phase II Trial in Men With Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Heath, Elisabeth I.; Smith, David C.; Rathkopf, Dana; Blackford, Amanda L.; Danila, Daniel C.; King, Serina; Frost, Anja; Ajiboye, A. Seun; Zhao, Ming; Mendonca, Janet; Kachhap, Sushant K.; Rudek, Michelle A.; Carducci, Michael A.

    2013-01-01

    Background. The antifungal drug itraconazole inhibits angiogenesis and Hedgehog signaling and delays tumor growth in murine prostate cancer xenograft models. We conducted a noncomparative, randomized, phase II study evaluating the antitumor efficacy of two doses of oral itraconazole in men with metastatic prostate cancer. Patients and Methods. We randomly assigned 46 men with chemotherapy-naïve metastatic castration-resistant prostate cancer (CRPC) to receive low-dose (200 mg/day) or high-dose (600 mg/day) itraconazole until disease progression or unacceptable toxicity. The primary endpoint was the prostate-specific antigen (PSA) progression-free survival (PPFS) rate at 24 weeks; a 45% success rate in either arm was prespecified as constituting clinical significance. Secondary endpoints included the progression-free survival (PFS) rate and PSA response rate (Prostate Cancer Working Group criteria). Exploratory outcomes included circulating tumor cell (CTC) enumeration, serum androgen measurements, as well as pharmacokinetic and pharmacodynamic analyses. Results. The high-dose arm enrolled to completion (n = 29), but the low-dose arm closed early (n = 17) because of a prespecified futility rule. The PPFS rates at 24 weeks were 11.8% in the low-dose arm and 48.0% in the high-dose arm. The median PFS times were 11.9 weeks and 35.9 weeks, respectively. PSA response rates were 0% and 14.3%, respectively. In addition, itraconazole had favorable effects on CTC counts, and it suppressed Hedgehog signaling in skin biopsy samples. Itraconazole did not reduce serum testosterone or dehydroepiandrostenedione sulfate levels. Common toxicities included fatigue, nausea, anorexia, rash, and a syndrome of hypokalemia, hypertension, and edema. Conclusion. High-dose itraconazole (600 mg/day) has modest antitumor activity in men with metastatic CRPC that is not mediated by testosterone suppression. PMID:23340005

  6. Vaccine Therapy and Pembrolizumab in Treating Patients With Hormone-Resistant, Metastatic Prostate Cancer

    Science.gov (United States)

    2016-06-22

    Hormone-Resistant Prostate Cancer; Metastatic Malignant Neoplasm in the Bone; Metastatic Malignant Neoplasm in the Soft Tissues; Metastatic Prostate Carcinoma; Prostate Adenocarcinoma; Recurrent Prostate Carcinoma; Stage IV Prostate Cancer

  7. New drug development in metastatic prostate cancer.

    Science.gov (United States)

    Armstrong, Andrew J; George, Daniel J

    2008-01-01

    In 2007, drug development in castration-resistant metastatic prostate cancer (CRPC) remains challenging, due to the number of potentially viable molecular targets and clinical trials available, the lack of established surrogates for overall survival, and competing causes of mortality. This review will highlight the highest impact phase II and phase III trials of novel agents in the current CRPC landscape, and focus on both molecular targets and clinical trial designs that are more likely to demonstrate clinical benefit. The need for tissue correlative studies for target evaluation and drug mechanism is stressed to continue to advance the field and to define biomarkers that may identify patient populations that may derive a greater benefit from these molecular agents.

  8. Enzalutamide in metastatic prostate cancer before chemotherapy

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana E

    2014-01-01

    BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have not rece......BACKGROUND: Enzalutamide is an oral androgen-receptor inhibitor that prolongs survival in men with metastatic castration-resistant prostate cancer in whom the disease has progressed after chemotherapy. New treatment options are needed for patients with metastatic prostate cancer who have...... not received chemotherapy, in whom the disease has progressed despite androgen-deprivation therapy. METHODS: In this double-blind, phase 3 study, we randomly assigned 1717 patients to receive either enzalutamide (at a dose of 160 mg) or placebo once daily. The coprimary end points were radiographic progression...... at the data-cutoff date (29% reduction in the risk of death; hazard ratio, 0.71; 95% CI, 0.60 to 0.84; Pchemotherapy (hazard ratio, 0.35), the time until the first...

  9. Multiple urinary bladder masses from metastatic prostate adenocarcinoma

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    Richard Choo

    2010-12-01

    Full Text Available We present an unusual case of metastatic prostate adenocarcinoma that manifested with multiple exophytic intravesical masses, mimicking a multifocal primary bladder tumor. Biopsy with immunohistochemical analysis confirmed metastatic prostate adenocarcinoma. The patient was treated palliatively with external beam radiotherapy to prevent possible symptoms from local tumor progression. This case illustrates that when a patient with known prostate cancer presents with multifocal bladder tumors, the possibility of metastatic prostate cancer should be considered.

  10. BRCA1 loss pre-existing in small subpopulations of prostate cancer is associated with advanced disease and metastatic spread to lymph nodes and peripheral blood

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    Bednarz, Natalia; Eltze, Elke; Semjonow, Axel; Rink, Michael; Andreas, Antje; Mulder, Lennart; Hannemann, Juliane; Fisch, Margit; Pantel, Klaus; Weier, Heinz-Ulrich G.; Bielawski, Krzysztof P.; Brandt, Burkhard

    2010-03-19

    A recent study concluded that serum prostate specific antigen (PSA)-based screening is beneficial for reducing the lethality of PCa, but was also associated with a high risk of 'overdiagnosis'. Nevertheless, also PCa patients who suffered from organ confined tumors and had negative bone scans succumb to distant metastases after complete tumor resection. It is reasonable to assume that those tumors spread to other organs long before the overt manifestation of metastases. Our current results confirm that prostate tumors are highly heterogeneous. Even a small subpopulation of cells bearing BRCA1 losses can initiate PCa cell regional and distant dissemination indicating those patients which might be at high risk of metastasis. A preliminary study performed on a small cohort of multifocal prostate cancer (PCa) detected BRCA1 allelic imbalances (AI) among circulating tumor cells (CTCs). The present analysis was aimed to elucidate the biological and clinical role of BRCA1 losses on metastatic spread and tumor progression in prostate cancer patients. Experimental Design: To map molecular progression in PCa outgrowth we used FISH analysis of tissue microarrays (TMA), lymph node sections and CTC from peripheral blood. We found that 14% of 133 tested patients carried monoallelic BRCA1 loss in at least one tumor focus. Extended molecular analysis of chr17q revealed that this aberration was often a part of larger cytogenetic rearrangement involving chr17q21 accompanied by AI of the tumor suppressor gene PTEN and lack of the BRCA1 promoter methylation. The BRCA1 losses correlated with advanced T stage (p < 0.05), invasion to pelvic lymph nodes (LN, p < 0.05) as well as BR (p < 0.01). Their prevalence was twice as high within 62 LN metastases (LNMs) as in primary tumors (27%, p < 0.01). The analysis of 11 matched primary PCa-LNM pairs confirmed the suspected transmission of genetic abnormalities between those two sites. In 4 of 7 patients with metastatic disease, BRCA1

  11. Immunotherapy in metastatic prostate cancer

    Science.gov (United States)

    Slovin, Susan F.

    2016-01-01

    Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit. PMID:27843208

  12. Immunotherapy in metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Susan F Slovin

    2016-01-01

    Full Text Available Introduction: Prostate cancer remains a challenge as a target for immunological approaches. The approval of the first cell-based immune therapy, Sipuleucel-T for prostate cancer introduced prostate cancer as a solid tumor with the potential to be influenced by the immune system. Methods: We reviewed articles on immunological management of prostate cancer and challenges that lie ahead for such strategies. Results: Treatments have focused on the identification of novel cell surface antigens thought to be unique to prostate cancer. These include vaccines against carbohydrate and blood group antigens, xenogeneic and naked DNA vaccines, and pox viruses used as prime-boost or checkpoint inhibitors. No single vaccine construct to date has resulted in a dramatic antitumor effect. The checkpoint inhibitor, anti-CTLA-4 has resulted in several long-term remissions, but phase III trials have not demonstrated an antitumor effect or survival benefit. Conclusions: Multiple clinical trials suggest that prostate cancer may not be optimally treated by single agent immune therapies and that combination with biologic agents, chemotherapies, or radiation may offer some enhancement of benefit.

  13. Prostate radiation in non-metastatic castrate refractory prostate cancer provides an interesting insight into biology of prostate cancer

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    Pascoe Abigail C

    2012-03-01

    Full Text Available Abstract Background The natural history of non-metastatic castrate refractory prostate cancer is unknown and treatment options are limited. We present a retrospective review of 13 patients with locally advanced or high risk prostate cancer, initially treated with hormone monotherapy and then treated with prostate radiation after becoming castration refractory. Findings Median PSA response following prostate radiation was 67.4%. Median time to biochemical progression following radiotherapy was 15 months and to detection of metastatic disease was 18.5 months. Median survival from castration resistance (to date of death or November 2011 was 60 months, with median survival from RT 42 months. Conclusion Prostate radiation appears to be beneficial even in patients with potential micrometastatic disease, which supports the hypothesis that the primary tumour is important in the progression of prostate cancer. These results are an interesting addition to the literature on the biology of prostate cancer especially as this data is unlikely to be available in the future due to combined prostate radiation and androgen deprivation therapy now being the standard of care.

  14. MOLECULAR MARKERS FOR METASTATIC PROSTATE ADENOCARCINOMA

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    I. S. Kunin

    2012-01-01

    Full Text Available The search of molecular markers of metastasing and prognosis in prostate cancer remains an urgent task. In this study, we investigated the relationship of gene expression heparanase-1 (HPSE1 and D-glucuronil C5-epimerase (GLCE with early disease relapse and metastasis of a 2,5−3 years after diagnosis. It was shown that the ratio of the expression levels of genes HPSE1/GLCE > 1 may serve as a prognostic relapse marker and trends of the tumour to metastasis. The data obtained suggest to use this option as a molecular marker for the diagnostics of metastatic process and the disease prognosis.

  15. Carcinoma of the prostate metastatic to the maxillary antrum.

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    Har-El, G; Avidor, I; Weisbord, A; Sidi, J

    1987-01-01

    Metastatic carcinoma of the maxillary antrum is an extreme rarity. Until 1980, less than 100 cases with distant primaries metastatic to the entire sinonasal tract had been reported. In a review of these cases, we found no mention of primary prostate cancer metastatic to the antrum. The purpose of this paper is to document the first case of this entity.

  16. The truth is in the water: metastatic prostate cancer presenting as an intermittent facial nerve palsy.

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    Wooles, N; Gupta, S; Wilkin-Crowe, H; Juratli, A

    2015-04-24

    An elderly man presented to the acute ear, nose and throat (ENT) services with a history of intermittent, self-limiting facial nerve palsy. Full ENT examination was normal, with all cranial nerves and peripheral neurology intact. Multiple imaging modalities suggested an aggressive bony lesion, secondary to locally advanced prostate malignancy with extensive metastatic infiltration. Prostate cancer is known to preferentially metastasise to bone and has been known to cause multiple cranial nerve palsies and ophthalmoplegia. This is the first case described in the literature of metastatic prostate cancer presenting with intermittent facial nerve palsy.

  17. Potential synergistic implications for stromal-targeted radiopharmaceuticals in bone-metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor

    2011-01-01

    Genetic heterogeneity and chemotherapy-resistant 'stem cells' represent two of the most pressing issues in devising new strategies for the treatment of advanced prostate cancer. Though curative strategies have long been present for men with localized disease, metastatic prostate cancer is currently incurable. Though substantial improvements in outcomes are now possible through the utilization of newly approved therapies, novel combinations are clearly needed. Herein we describe potentially synergistic interactions between bone stromal-targeted radiopharmaceuticals and other therapies for treatment of bone-metastatic prostate cancer. Radiation has long been known to synergize with cytotoxic chemotherapies and recent data also suggest the possibility of synergy when combining radiation and immune-based strategies. Combination therapies will be required to substantially improve survival for men with castrate-resistant metastatic prostate cancer and we hypothesize that bone-targeted radiopharmaceuticals will play an important role in this process.

  18. Metronomic Treatment with Low-Dose Trofosfamide Leads to a Long-Term Remission in a Patient with Docetaxel-Refractory Advanced Metastatic Prostate Cancer

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    Jochen Greiner

    2010-01-01

    Full Text Available The treatment of metastatic prostate cancer patients refractory to androgen withdrawal and docetaxel therapy is currently discouraging and new therapeutic approaches are vastly needed. Here, we report a long-term remission over one year in a 68-year-old patient with metastatic docetaxel-refractory prostate cancer employing low-dose trofosfamide. The patient suffered from distant failure with several bone lesions and lymph node metastases depicted by a (11 C-Choline positron emission tomography/computerized tomography (PET/CT. After initiation of trofosfamide 100 mg taken orally once a day we observed a steadily decreasing PSA value from initial 46.6 down to 2.1 g/l. The Choline-PET/CT was repeated after 10 months of continuous therapy and demonstrated a partial remission of the bone lesions and a regression of all involved lymph nodes but one. Taken together we found an astonishing and durable activity of the alkylating agent trofosfamide given in a metronomic fashion. We rate the side effects as low and state an excellent therapeutic ratio of this drug in our patient.

  19. Metastatic Prostate Adenocarcinoma Presenting Central Diabetes Insipidus

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    Hakkı Yılmaz

    2012-01-01

    Full Text Available The pituitary gland and infundibulum can be involved in a variety of medical conditions, including infiltrative diseases, fungal infections, tuberculosis, and primary and metastatic tumors. Metastases to the pituitary gland are absolutely rare, and they are generally secondary to pulmonary carcinoma in men and breast carcinoma in women. Pituitary metastases more commonly affect the posterior lobe and the infundibulum than the anterior lobe. The posterior lobe involvement may explain why patients with pituitary metastases frequently present with diabetes insipidus. We are presenting a case report of a 78-year-old male patient who had metastatic prostate with sudden onset of polyuria and persistent thirst. He had no electrolyte imbalance except mild hypernatremia. The MRI scan of the brain yielded a suspicious area in pituitary gland. A pituitary stalk metastasis was found on magnetic resonance imaging (MRI of pituitary. Water deprivation test was compatible with DI. A clinical response to nasal vasopressin was achieved and laboratory results revealed central diabetes insipidus. As a result, the intrasellar and suprasellar masses decreased in size, and urinary output accordingly decreased.

  20. 雄激素非依赖性晚期转移性前列腺癌生存预后分析%The survival analysis of the advanced metastatic castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    马春光; 施国海; 秦晓健; 林国文; 杨立峰; 杨柏帅; 肖文军; 叶定伟; 姚旭东; 张世林; 戴波; 张海梁; 朱耀; 沈益君; 朱一平

    2009-01-01

    目的 分析雄激素非依赖性晚期转移性前列腺癌的预后相关因素.方法 1996年12月至2008年3月250例晚期转移性前列腺癌患者在内分泌治疗期间进展为雄激素非依赖性前列腺癌,对其进行随访,末次随访时间为2008年3月31日,中位随访时间为24个月(3~135个月).末次随访时131例生存,105例死亡,14例失访.利用统计学软件进行生存预后分析.结果 中位生存时间为30个月.1年牛存率79%,2年生存率59%,3年生存率41%.单因素分析及多因素分析显示:内分泌治疗过程中PSA最低值、达到PSA最低值时间、进展为雄激素非依赖性前列腺癌时PSA速率、内分泌治疗有效时间为独立预后冈素.结论 内分泌治疗过程中PSA最低值、达到PSA最低值时间、进展为雄激素非依赖性前列腺癌时的PSA速率和内分泌治疗有效时间为雄激素非依赖性晚期转移性前列腺癌生存时间的独立预后因素.%Objective To analyze predictive factors of advanced metastatic castration-resistant prostate cancer.Methods From December 1996 to March 2008,250 cases of advanced metastatic prostate cancer progressed into the stage of hormonal independent prostate cancer.The last follow-up date was 31 March 2008 and the median follow-up time was 24 months.During the follow-up,131 cases were alive,105cases were dead and 14 cases were lost to follow-up.Clinical and pathological information of the cases was analyzed to find the predictive factors that related to the prognosis.Results The median survival time of advanced metastatic castration-resistant prostate cancer was 30 months,and the one-year,two-year,three-year survival rate was 79%,59%,and 41%.The univariate analysis indicated that prostate specific antigen (PSA) at diagnosis,clinical stage,the PSA nadir during hormonal therapy,the time form the start of hormonal therapy to the PSA nadir,the time of response duration during hormonal therapy,PSA velocity (PSAV) and PSA doubling

  1. Sipuleucel-T for the treatment of advanced prostate cancer.

    Science.gov (United States)

    Frohlich, Mark W

    2012-06-01

    Sipuleucel-T is an autologous cellular immunotherapy designed to stimulate an immune response to prostate cancer that prolongs the overall survival of men with asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer (CRPC). The clinical development program and key efficacy, safety, and immune response findings from the phase III studies are presented. The integration of sipuleucel-T into the treatment paradigm of advanced prostate cancer and future directions for research are discussed.

  2. Prostate Cancer Stem Cells: Research Advances.

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    Jaworska, Dagmara; Król, Wojciech; Szliszka, Ewelina

    2015-01-01

    Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  3. Prostate Cancer Stem Cells: Research Advances

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    Dagmara Jaworska

    2015-11-01

    Full Text Available Cancer stem cells have been defined as cells within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. Experimental evidence showed that these highly tumorigenic cells might be responsible for initiation and progression of cancer into invasive and metastatic disease. Eradicating prostate cancer stem cells, the root of the problem, has been considered as a promising target in prostate cancer treatment to improve the prognosis for patients with advanced stages of the disease.

  4. MicroRNAs associated with metastatic prostate cancer.

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    Akira Watahiki

    Full Text Available OBJECTIVE: Metastasis is the most common cause of death of prostate cancer patients. Identification of specific metastasis biomarkers and novel therapeutic targets is considered essential for improved prognosis and management of the disease. MicroRNAs (miRNAs form a class of non-coding small RNA molecules considered to be key regulators of gene expression. Their dysregulation has been shown to play a role in cancer onset, progression and metastasis, and miRNAs represent a promising new class of cancer biomarkers. The objective of this study was to identify down- and up-regulated miRNAs in prostate cancer that could provide potential biomarkers and/or therapeutic targets for prostate cancer metastasis. METHODS: Next generation sequencing technology was applied to identify differentially expressed miRNAs in a transplantable metastatic versus a non-metastatic prostate cancer xenograft line, both derived from one patient's primary cancer. The xenografts were developed via subrenal capsule grafting of cancer tissue into NOD/SCID mice, a methodology that tends to preserve properties of the original cancers (e.g., tumor heterogeneity, genetic profiles. RESULTS: Differentially expressed known miRNAs, isomiRs and 36 novel miRNAs were identified. A number of these miRNAs (21/104 have previously been reported to show similar down- or up-regulation in prostate cancers relative to normal prostate tissue, and some of them (e.g., miR-16, miR-34a, miR-126*, miR-145, miR-205 have been linked to prostate cancer metastasis, supporting the validity of the analytical approach. CONCLUSIONS: The use of metastatic and non-metastatic prostate cancer subrenal capsule xenografts derived from one patient's cancer makes it likely that the differentially expressed miRNAs identified in this study include potential biomarkers and/or therapeutic targets for human prostate cancer metastasis.

  5. Radium-223 in metastatic castration resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Winston Vuong; Oliver Sartor; Sumanta K Pal

    2014-01-01

    In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival beneift in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently) radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89), radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors inlfuencing clinical implementation.

  6. Radium-223 in metastatic castration resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Winston Vuong

    2014-06-01

    Full Text Available In 2004, docetaxel was approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC. For the next several years, there was a lull in drug approvals. However, from 2010 onwards, 5 additional therapies have been approved on the basis of showing a survival benefit in phase III studies. These agents include sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and (most recently radium-223. Amongst radiopharmaceuticals currently used for advanced prostate cancer (e.g. samarium-153 and strontium-89, radium-223 possesses several unique properties. As an alpha-emitting compound, the agent produces a high-energy output over a short range, facilitating selective destruction of tissue within the bone in the region of osteoblastic lesions while sparing surrounding normal tissue. The current review will outline biological rationale for radium-223 and also provide an overview of preclinical and clinical development of the agent. Rational sequencing of radium-223 and combinations, in the increasingly complex landscape of mCRPC will be discussed, along with factors influencing clinical implementation.

  7. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma

    OpenAIRE

    Zardawi, Ibrahim; Chong, Peter

    2016-01-01

    Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  8. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma.

    Science.gov (United States)

    Zardawi, Ibrahim; Chong, Peter

    2016-07-01

    Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  9. Metastatic Prostate Cancer to the Urethra Masquerading as Urothelial Carcinoma

    Directory of Open Access Journals (Sweden)

    Ibrahim Zardawi

    2016-07-01

    Full Text Available Tumors of the urethra, whether primary or metastatic, are very rare. The true nature of urethral neoplasm is not always obvious clinically nor in routine histological sections. Immunostains should be performed on such lesions because of management implications. We present a case of multiple metastases to the urethra from a prostatic carcinoma, masquerading as multiple urothelial carcinomas. Pathologists and urologists should be aware of the possibility of metastasis from the prostate.

  10. Non-invasive actionable biomarkers for metastatic prostate cancer

    Directory of Open Access Journals (Sweden)

    Jun Luo

    2016-10-01

    Full Text Available In the current clinical setting, many disease management options are available for men diagnosed with prostate cancer. For metastatic prostate cancer, first-line therapies almost always involve agents designed to inhibit androgen receptor (AR signaling. Castration-resistant prostate cancers (CRPCs that arise following first-line androgen deprivation therapies (ADT may continue to respond to additional lines of AR-targeting therapies (abiraterone and enzalutamide, chemotherapies (docetaxel and cabazitaxel, bone-targeting Radium-223 therapy, and immunotherapy sipuleucel-T. The rapidly expanding therapies for CRPC is expected to transform this lethal disease into one that can be managed for prolonged period of time. In the past 3 years, a number of promising biomarkers that may help to guide treatment decisions have been proposed and evaluated, including androgen receptor splice variant-7 (AR-V7, a truncated AR lacking the ligand-binding domain (LBD and mediate constitutively-active AR signaling. Putative treatment selection markers such as AR-V7 may further improve survival benefit of existing therapies and help to accelerate development of new agents for metastatic prostate cancer. In the metastatic setting, it is important to consider compatibility between the putative biomarker with non-invasive sampling. In this review, biomarkers relevant to the setting of metastatic prostate cancer are discussed with respect to a number of key attributes critical for clinical development of non-invasive, actionable markers. It is envisioned that biomarkers for metastatic prostate cancer will continue to be discovered, developed, and refined to meet the unmet needs in both standard-of-care and clinical trial settings.

  11. Targeting bone physiology for the treatment of metastatic prostate cancer.

    Science.gov (United States)

    Autio, Karen A; Morris, Michael J

    2013-03-01

    Metastatic prostate cancer has a unique predilection for bone that can lead to significant clinical sequelae, such as fracture and cord compression. This tropism for bone yields not only clinical challenges, but also opportunities to understand the tumor biology in bone and to develop relevant therapeutic strategies. The process by which tumor cells migrate to bone, remain dormant, and then colonize and expand is based on complex interactions between prostate cancer tumor cells and the host microenvironment. This review will provide an overview of these interactions as well as therapies targeting osseous metastases in castration-resistant prostate cancer.

  12. Abiraterone in metastatic prostate cancer without previous chemotherapy

    NARCIS (Netherlands)

    Ryan, C.J.; Smith, M.R.; Bono, J. De; Molina, A.; Logothetis, C.J.; Souza, P. de; Fizazi, K.; Mainwaring, P.; Piulats, J.M.; Ng, S.; Carles, J.; Mulders, P.F.A.; Basch, E.; Small, E.J.; Saad, F.; Schrijvers, D.; Poppel, H. van; Mukherjee, S.D.; Suttmann, H.; Gerritsen, W.R.; Flaig, T.W.; George, D.J.; Yu, E.Y.; Efstathiou, E.; Pantuck, A.; Winquist, E.; Higano, C.S.; Taplin, M.E.; Park, Y.; Kheoh, T.; Griffin, T.; Scher, H.I.; Rathkopf, D.E.

    2013-01-01

    BACKGROUND: Abiraterone acetate, an androgen biosynthesis inhibitor, improves overall survival in patients with metastatic castration-resistant prostate cancer after chemotherapy. We evaluated this agent in patients who had not received previous chemotherapy. METHODS: In this double-blind study, we

  13. Redefining Hormone Sensitive Disease in Advanced Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Xiaoyu Hou

    2012-01-01

    Full Text Available Prostate cancer is the most common cancer among men in the United States. For decades, the cornerstone of medical treatment for advanced prostate cancer has been hormonal therapy, intended to lower testosterone levels, known as Androgen Deprivation Therapy (ADT. The development of hormone-resistant prostate cancer (now termed castration-resistant prostate cancer:CRPC remains the key roadblock in successful long-term management of prostate cancer. New advancements in medical therapy for prostate cancer have added to the hormonal therapy armamentarium. These new therapeutic agents not only provide a survival benefit but also show potential for reversing hormonal resistance in metastatic CRPC, and thus redefining hormonally sensitive disease.

  14. Critical questions in metastatic castration-resistant prostate cancer: Integrating emerging clinical evidence and guideline recommendations

    Directory of Open Access Journals (Sweden)

    Mohamed Ali

    2016-01-01

    Full Text Available Metastatic castration-resistant prostate cancer (CRPC typically confers a poor prognosis, however, novel advances in treatment options, as well as biomarkers for monitoring disease response and progression, have recently helped improve survival rates. Additionally, new guidelines provide some direction on incorporating these new treatments but some confusion still exists among clinicians about best methods for initiating treatment and the optimal sequencing of agents to prolong survival. In this article, we review the literature and answer some frequently asked questions about treating men with metastatic CRPC, including choosing a first-line treatment, monitoring treatment response, and proceeding to additional lines of therapy.

  15. Critical questions in metastatic castration-resistant prostate cancer: Integrating emerging clinical evidence and guideline recommendations

    OpenAIRE

    2016-01-01

    Metastatic castration-resistant prostate cancer (CRPC) typically confers a poor prognosis, however, novel advances in treatment options, as well as biomarkers for monitoring disease response and progression, have recently helped improve survival rates. Additionally, new guidelines provide some direction on incorporating these new treatments but some confusion still exists among clinicians about best methods for initiating treatment and the optimal sequencing of agents to prolong survival. In ...

  16. Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jean-Christophe Brisset

    Full Text Available Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05. These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease.

  17. Hyaluronan-Based Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2015-07-01

    cancer cell lines (PC3, DU145) correlate with greater tumorigenic and metastatic properties over prostate cancer cell lines (LNCaP) that do not...tumorigenic and metastatic properties (right). B) Cy5.5-labeled HA-NPs (50 µg/mL) or HA polymer (234.4 kDa) were incubated for 2 hours with PC3 cells. C...lysed with DISC IP lysis buffer (30 mM Tris, pH 7.4, 150 mM NaCl, 10% glycerol , 1% Triton X-100 with 1 mM PMSF, and 1 μg/mL each of aprotinin, leupeptin

  18. Molecular Heterogeneity in Primary and Metastatic Prostate Tumor Tissue

    Science.gov (United States)

    2014-10-01

    her expertise in prostate cancer epidemiology, has coordinated meetings to discuss the study progress with collaborators, and has begun specimen and...Development of a tissue resource that combines within-person primary and lymph node-positive prostate cancer specimens. This resource is coordinated in...melatonin levels, sleep disruption, and risk of prostate cancer in elderly men. European Urology 2014 Advance online publication. doi: 10.1016/j.eururo

  19. Metastatic Breast Carcinoma to the Prostate Gland.

    Science.gov (United States)

    Kapp, Meghan E; Giannico, Giovanna A; Desouki, Mohamed Mokhtar

    2016-01-01

    Cancer of the male breast is an uncommon event with metastases to the breast occurring even less frequently. Prostate carcinoma has been reported as the most frequent primary to metastasize to the breast; however, the reverse has not been previously reported. Herein, we present, for the first time, a case of breast carcinoma metastasizing to the prostate gland. Prostate needle core biopsy revealed infiltrative nests of neoplastic epithelioid cells, demonstrated by immunohistochemistry (IHC) to be positive for GATA3 and ER and negative for PSA and P501S. A prostate cocktail by IHC study demonstrated lack of basal cells (p63 and CK903) and no expression of P501S. The patient's previous breast needle core biopsy showed strong ER positivity and negative staining for PR and HER2. Similar to the prostate, the breast was negative for CK5/6, p63, and p40. This case demonstrates the importance of considering a broad differential diagnosis and comparing histology and IHC to prior known malignancies in the setting of atypical presentation or rare tumors.

  20. Metastatic Breast Carcinoma to the Prostate Gland

    Directory of Open Access Journals (Sweden)

    Meghan E. Kapp

    2016-01-01

    Full Text Available Cancer of the male breast is an uncommon event with metastases to the breast occurring even less frequently. Prostate carcinoma has been reported as the most frequent primary to metastasize to the breast; however, the reverse has not been previously reported. Herein, we present, for the first time, a case of breast carcinoma metastasizing to the prostate gland. Prostate needle core biopsy revealed infiltrative nests of neoplastic epithelioid cells, demonstrated by immunohistochemistry (IHC to be positive for GATA3 and ER and negative for PSA and P501S. A prostate cocktail by IHC study demonstrated lack of basal cells (p63 and CK903 and no expression of P501S. The patient’s previous breast needle core biopsy showed strong ER positivity and negative staining for PR and HER2. Similar to the prostate, the breast was negative for CK5/6, p63, and p40. This case demonstrates the importance of considering a broad differential diagnosis and comparing histology and IHC to prior known malignancies in the setting of atypical presentation or rare tumors.

  1. Stromal targeted therapy in bone metastatic prostate cancer: promise delivered

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor; William Goeckeler; Oyvind Bruland

    2011-01-01

    The ability of epithelial neoplasms to evade both hormonal and cytotoxic therapies is self-evident as the common carcinomas (lung,stomach,breast,colon and prostate) at their metastatic stage are rarely curable with current therapies.Though the precise reasons for incurability are debated,virtually all agree that tumor genetic heterogeneity makes eradication of the tumor difficult given ‘Darwinian' selection processes that are associated with the emergence of drug-resistant cellular clones.

  2. Targeting Met and VEGFR Axis in Metastatic Castration-Resistant Prostate Cancer: 'Game Over'?

    Science.gov (United States)

    Modena, Alessandra; Massari, Francesco; Ciccarese, Chiara; Brunelli, Matteo; Santoni, Matteo; Montironi, Rodolfo; Martignoni, Guido; Tortora, Giampaolo

    2016-08-01

    Despite recent advances that have been made in the therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC), effective management of bone metastases remains a key goal not yet reached. The receptor tyrosine kinase MET and the vascular endothelial growth factor receptor (VEGFR) seem to play an important role in prostate cancer progression and pathological bone turnover, representing potential targets for improving clinical outcomes in mCRPC. Studies evaluating agents that target one or both these pathways have demonstrated modest activity but no improvement in overall survival. Nevertheless, this therapeutic strategy seems to still be a promising and engaging area of prostate cancer research and the interest in better understanding the MET/VEGFR axis and the mechanism of action of these inhibitors is growing. This review describes the rationale for targeting MET and VEGFR pathway in mCRPC and provides the clinical data available to date and an update on ongoing trials.

  3. Evaluation of metastatic potential of prostate cancer

    Directory of Open Access Journals (Sweden)

    Yoshitomo Chihara

    2011-06-01

    Full Text Available We aimed to establish a method for evaluating malignant potential of prostate cancer using prostatic core needle biopsy (PCNB before prostatectomy. If we can know the final pathological stage before treatment, we can select the most suitable therapeutic tactics. We then examined the expression of E-cadherin and type IV collagenase (MMP-9/-2, which play essential role in cancer cell invasion and metastasis. The expression ratio of MMP-9/-2 to E-cadherin (MER is revealed as the relevant marker correlated with the final pathological stage and Gleason score by prostatectomy specimens. We next confirmed the significance of MER in PCNB, which means PCNB MER enables the prediction of the final pathologic stage at the cancer diagnosis. However, the methodology measuring MER is complicated to produce an observer-to-observer deviation. We then establish a bicolor fluorescent ISH (bicolor FISH with a computerized fluorescence detector- based system. By this method, we can reduce an observer-to-observer deviation and a slide-to-slide deviation. The bicolor FISH-based MER is a useful tool for the preoperative evaluation of the final pathologic stage, by which we can assure a decision of prostatectomy indication.

  4. Targeted treatment of metastatic castration-resistant prostate cancer with sipuleucel-T immunotherapy

    NARCIS (Netherlands)

    Mulders, P.F.; Santis, M. de; Powles, T.; Fizazi, K.

    2015-01-01

    CONTEXT: Prostate cancer remains highly prevalent and has a poor clinical outcome once metastatic. Sipuleucel-T is an autologous cellular immunotherapy approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T treatment extends survival but is independent of

  5. ERBB2 increases metastatic potentials specifically in androgen-insensitive prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Jessica Tome-Garcia

    Full Text Available Despite all the blood-based biomarkers used to monitor prostate cancer patients, prostate cancer remains as the second common cause of cancer mortality in men in the United States. This is largely due to a lack of understanding of the molecular pathways that are responsible for the aggressive forms of prostate cancers, the castrate-resistant prostate cancer and the metastatic prostate cancer. Cell signaling pathways activated by the ERBB2 oncogene or the RAS oncogene are frequently found to be altered in metastatic prostate cancers. To evaluate and define the role of the ERBB2/RAS pathway in prostate cancer metastasis, we have evaluated the impact of ERBB2- or RAS-overexpression on the metastatic potentials for four prostate cancer cell lines derived from tumors with different androgen sensitivities. To do so, we transfected the human DU145, LnCaP, and PC3 prostate cancer cells and the murine Myc-CaP prostate cancer cells with the activated form of ERBB2 or H-RAS and assessed their metastatic potentials by three complementary assays, a wound healing assay, a transwell motility assay, and a transwell invasion assay. We showed that while overexpression of ERBB2 increased the metastatic potential of the androgen-insensitive prostate cancer cells (i.e. PC3 and DU145, it did not affect metastatic potentials of the androgen-sensitive prostate cancer cells (i.e. LnCaP and Myc-CaP. In contrast, overexpression of H-RAS only increased the cell motility of Myc-CaP cells, which overexpress the human c-MYC oncogene. Our data suggest that ERBB2 collaborates with androgen signaling to promote prostate cancer metastasis, and that although RAS is one of the critical downstream effectors of ERBB2, it does not phenocopy ERBB2 for its impact on the metastatic potentials of prostate cancer cell lines.

  6. High Throughput Sequencing of Germline and Tumor from Men With Early-Onset Metastatic Prostate Cancer

    Science.gov (United States)

    2014-10-01

    challenge, Dr. Tomlins has continued to develop state of the art technologies to use formalin-fixed paraffin-embedded (FFPE) prostate cancer specimens...men with early-onset, metastatic prostate cancer PRINCIPAL INVESTIGATOR: Kathleen A. Cooney, M.D. CONTRACTING ORGANIZATION...High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer 5b. GRANT NUMBER W81XWH-13-1-0371 5c

  7. Sipuleucel-T: immunotherapy for advanced prostate cancer

    OpenAIRE

    Olson BM; McNeel DG

    2011-01-01

    Brian M Olson, Douglas G McNeelUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USAAbstract: Prostate cancer continues to be one of the most serious afflictions of men of advanced age, remaining the most commonly diagnosed and second leading cause of cancer-related deaths in American men. The treatment options for patients with incurable metastatic, castrate-resistant disease have long focused on various chemotherapeutic approaches, which provide a ...

  8. Sipuleucel-T: immunotherapy for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Olson BM

    2011-05-01

    Full Text Available Brian M Olson, Douglas G McNeelUniversity of Wisconsin Carbone Cancer Center, University of Wisconsin-Madison, Madison, WI, USAAbstract: Prostate cancer continues to be one of the most serious afflictions of men of advanced age, remaining the most commonly diagnosed and second leading cause of cancer-related deaths in American men. The treatment options for patients with incurable metastatic, castrate-resistant disease have long focused on various chemotherapeutic approaches, which provide a slight survival benefit while being associated with potentially significant side effects. However, the recent approval of sipuleucel-T has given patients with advanced disease an additional treatment option that has demonstrated benefit without the side effects associated with chemotherapy. Sipuleucel-T is an antigen-presenting cell-based active immunotherapy that utilizes a patient's own immune cells, presumably to activate an antigen-specific immune response against tumor cells. This review focuses on the development and implementation of sipuleucel-T as a therapy for prostate cancer. Specifically, we present some of the issues associated with the management of advanced prostate cancer, the research and development that led to the approval of sipuleucel-T, how the approval of sipuleucel-T could change the clinical management of prostate cancer, and current and future areas of investigation that are being pursued with regard to sipuleucel-T and other treatments for advanced prostate cancer.Keywords: sipuleucel-T, prostatic acid phosphatase, granulocyte-macrophage colonystimulating factor

  9. Sipuleucel-T: immunotherapy for advanced prostate cancer.

    Science.gov (United States)

    Olson, Brian M; McNeel, Douglas G

    2011-05-03

    Prostate cancer continues to be one of the most serious afflictions of men of advanced age, remaining the most commonly diagnosed and second leading cause of cancer-related deaths in American men. The treatment options for patients with incurable metastatic, castrate-resistant disease have long focused on various chemotherapeutic approaches, which provide a slight survival benefit while being associated with potentially significant side effects. However, the recent approval of sipuleucel-T has given patients with advanced disease an additional treatment option that has demonstrated benefit without the side effects associated with chemotherapy. Sipuleucel-T is an antigen-presenting cell-based active immunotherapy that utilizes a patient's own immune cells, presumably to activate an antigen-specific immune response against tumor cells. This review focuses on the development and implementation of sipuleucel-T as a therapy for prostate cancer. Specifically, we present some of the issues associated with the management of advanced prostate cancer, the research and development that led to the approval of sipuleucel-T, how the approval of sipuleucel-T could change the clinical management of prostate cancer, and current and future areas of investigation that are being pursued with regard to sipuleucel-T and other treatments for advanced prostate cancer.

  10. Increased survival in men with metastatic prostate cancer receiving chemo and hormone therapy

    Science.gov (United States)

    Men with hormone-sensitive metastatic prostate cancer who received the chemotherapy drug docetaxel given at the start of standard hormone therapy lived longer than patients who received hormone therapy alone, according to early results from a NIH-supporte

  11. Estramustine phosphate versus placebo as second line treatment after orchiectomy in patients with metastatic prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Asmussen, C;

    1997-01-01

    We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer.......We compared the effect of 560 mg. estramustine phosphate daily to placebo as a supplement to standard palliative therapy in patients with progressive disease after bilateral orchiectomy as first line therapy for metastatic prostate cancer....

  12. Targeted treatment of metastatic castration-resistant prostate cancer with sipuleucel-T immunotherapy

    OpenAIRE

    Mulders, Peter F.; Santis, Maria; Powles, Thomas; Fizazi, Karim

    2015-01-01

    Context Prostate cancer remains highly prevalent and has a poor clinical outcome once metastatic. Sipuleucel-T is an autologous cellular immunotherapy approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Sipuleucel-T treatment extends survival but is independent of traditional short-term markers of treatment response observed with chemotherapy and contemporary hormonal treatments. Therefore, it is essential that clinicians understand the mechanism of action o...

  13. Sleeping Beauty screen reveals Pparg activation in metastatic prostate cancer.

    Science.gov (United States)

    Ahmad, Imran; Mui, Ernest; Galbraith, Laura; Patel, Rachana; Tan, Ee Hong; Salji, Mark; Rust, Alistair G; Repiscak, Peter; Hedley, Ann; Markert, Elke; Loveridge, Carolyn; van der Weyden, Louise; Edwards, Joanne; Sansom, Owen J; Adams, David J; Leung, Hing Y

    2016-07-19

    Prostate cancer (CaP) is the most common adult male cancer in the developed world. The paucity of biomarkers to predict prostate tumor biology makes it important to identify key pathways that confer poor prognosis and guide potential targeted therapy. Using a murine forward mutagenesis screen in a Pten-null background, we identified peroxisome proliferator-activated receptor gamma (Pparg), encoding a ligand-activated transcription factor, as a promoter of metastatic CaP through activation of lipid signaling pathways, including up-regulation of lipid synthesis enzymes [fatty acid synthase (FASN), acetyl-CoA carboxylase (ACC), ATP citrate lyase (ACLY)]. Importantly, inhibition of PPARG suppressed tumor growth in vivo, with down-regulation of the lipid synthesis program. We show that elevated levels of PPARG strongly correlate with elevation of FASN in human CaP and that high levels of PPARG/FASN and PI3K/pAKT pathway activation confer a poor prognosis. These data suggest that CaP patients could be stratified in terms of PPARG/FASN and PTEN levels to identify patients with aggressive CaP who may respond favorably to PPARG/FASN inhibition.

  14. Activation of the hedgehog pathway in advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    McCormick Frank

    2004-10-01

    Full Text Available Abstract Background The hedgehog pathway plays a critical role in the development of prostate. However, the role of the hedgehog pathway in prostate cancer is not clear. Prostate cancer is the second most prevalent cause of cancer death in American men. Therefore, identification of novel therapeutic targets for prostate cancer has significant clinical implications. Results Here we report that activation of the hedgehog pathway occurs frequently in advanced human prostate cancer. We find that high levels of hedgehog target genes, PTCH1 and hedgehog-interacting protein (HIP, are detected in over 70% of prostate tumors with Gleason scores 8–10, but in only 22% of tumors with Gleason scores 3–6. Furthermore, four available metastatic tumors all have high expression of PTCH1 and HIP. To identify the mechanism of the hedgehog signaling activation, we examine expression of Su(Fu protein, a negative regulator of the hedgehog pathway. We find that Su(Fu protein is undetectable in 11 of 27 PTCH1 positive tumors, two of them contain somatic loss-of-function mutations of Su(Fu. Furthermore, expression of sonic hedgehog protein is detected in majority of PTCH1 positive tumors (24 out of 27. High levels of hedgehog target genes are also detected in four prostate cancer cell lines (TSU, DU145, LN-Cap and PC3. We demonstrate that inhibition of hedgehog signaling by smoothened antagonist, cyclopamine, suppresses hedgehog signaling, down-regulates cell invasiveness and induces apoptosis. In addition, cancer cells expressing Gli1 under the CMV promoter are resistant to cyclopamine-mediated apoptosis. All these data suggest a significant role of the hedgehog pathway for cellular functions of prostate cancer cells. Conclusion Our data indicate that activation of the hedgehog pathway, through loss of Su(Fu or overexpression of sonic hedgehog, may involve tumor progression and metastases of prostate cancer. Thus, targeted inhibition of hedgehog signaling may have

  15. Urothelial-Type adenocarcinoma of the prostate mimicking metastatic colorectal adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Brian P. Adley

    2006-12-01

    Full Text Available Adenocarcinoma arising in urinary bladder or prostatic urethra is uncommon. When they occur, the tumor can be mistaken for metastatic lesions, especially from the colon. Here we report the fifth case of a primary urothelial-type adenocarcinoma arising in the prostate which showed enteric differentiation. The patient was a 55 year-old male whose prostatic needle core biopsy showed a high grade adenocarcinoma which was initially thought to be metastatic colon cancer. A follow-up colonoscopy was unremarkable. Subsequent prostatectomy revealed a high grade adenocarcinoma which was positive for cytokeratins 7 and 20, carcinoembryonic antigen, CDX2, and high molecular weight cytokeratin, and negative for prostate specific antigen, prostate specific acid phosphatase and AMACR. A diagnosis of urothelial-type adenocarcinoma of the prostate was rendered. We review the literature regarding this entity, and discuss the differential diagnosis, emphasizing utility of immunohistochemistry in making the diagnosis. Finally, we speculate on the behavior of these rare tumors.

  16. CURRENT POSSIBILITIES OF TREATMENT FOR VISCERAL METASTASES IN PATIENTS WITH METASTATIC CASTRATION-REFRACTORY PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2014-07-01

    Full Text Available Medications increasing the survival of patients with metastatic castration-refractory prostate cancer (CRPC are lacking today. In the past 3 years, in the pharmaceutical market there have been a few novel drugs to treat progressive prostate cancer. Abiraterone acetate is an androgen synthesis inhibitor, which is also used to increase the survival of patients with metastatic CRPC that progresses after chemotherapy. The results of treatment for metastatic CRPC depend on a number of factors. Visceral metastases are poor predictors of the course of the disease. The results of abiraterone acetate treatment were analyzed in CRPC patients with visceral metastases.

  17. Successful treatment of metastatic androgen-independent prostate carcinoma in a transsexual patient.

    Science.gov (United States)

    Dorff, Tanya B; Shazer, Ronald L; Nepomuceno, Edward M; Tucker, Steven J

    2007-06-01

    The occurrence of prostate carcinoma in transsexual patients has rarely been reported. These cases present a unique challenge in that such patients are effectively receiving androgen deprivation therapy. By definition, their disease is androgen-independent prostate cancer, and the role of local therapy is undefined. We report on a male-to-female transsexual patient with metastatic prostate cancer treated successfully with combination chemotherapy after previous standard therapy failed.

  18. TH-E-BRF-08: Subpopulations of Similarly-Responding Lesions in Metastatic Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lin, C; Harmon, S; Perk, T; Jeraj, R [University of Wisconsin - Madison, Madison, WI (United States)

    2014-06-15

    population- and patient-level clustering, indicating that PET-based response features may be used to quantify disease heterogeneity in advanced metastatic disease. This method for categorizing lesion response could help in identifying lesions with similar phenotypic- or genetic-based resistances to therapy. Research Supported by the Prostate Cancer Foundation.

  19. Sipuleucel-T: in metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Plosker, Greg L

    2011-01-01

    Sipuleucel-T is an autologous active cellular immunotherapy used in the treatment of men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (CRPC). It is the first therapeutic cancer vaccine to receive US FDA approval. Approximately 3 days prior to each infusion of sipuleucel-T, patients undergo a leukapheresis procedure for collection of autologous peripheral blood mononuclear cells. Preparation of sipuleucel-T involves enrichment for antigen-presenting cells from the leukapheresis product and activation ex vivo with a recombinant fusion protein (PA2024). In the randomized, double-blind, placebo-controlled IMPACT study in patients with metastatic CRPC, sipuleucel-T was associated with a 22% relative reduction in the risk of death (hazard ratio 0.78; p = 0.03), which was the primary endpoint of the trial. After a median follow-up period of 34.1 months, median survival was 4.1 months longer with sipuleucel-T than placebo (25.8 vs 21.7 months). There was no significant between-group difference for the median time to objective disease progression (a secondary endpoint). Almost all patients treated with sipuleucel-T in clinical trials reported an adverse event, although these were mild or moderate in severity (grade 1 or 2) in most patients. The most common adverse events (e.g. infusion-related events, such as chills and fever) generally occurred within the first day after administration of sipuleucel-T and resolved within 2 days.

  20. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Oliver Sartor

    2014-06-01

    Full Text Available Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC. Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

  1. Treatment sequencing in metastatic castrate-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Oliver Sartor; Silke Gillessen

    2014-01-01

    Six different treatments have demonstrated improved survival in phase III trials targeted to patients with metastatic castration-resistant prostate cancer (mCRPC). Front-line therapeutic options for mCRPC include docetaxel, sipuleucel-T, abiraterone and radium-223. Post-docetaxel options include cabazitaxel, abiraterone, enzalutamide and radium-223. Despite much progress in recent years, much is yet unknown and debates occur over optimal treatment choices and sequences. None of the new agents have been compared to one another, thus physicians in practice today must make choices based on non-randomized comparisons, toxicity considerations and various assumptions. Abiraterone is now moving into the front line mCRPC space given recent regulatory approvals and enzalutamide will follow soon. Both of the hormonal agents have less toxicity when compared to chemotherapeutic options and both of these hormonal agents are expected to be used in a considerable number of mCRPC patients in the years ahead. Little data are available for the post-abiraterone or post-enzalutamide setting. In this review the currently available sequencing data are summarized and interpreted. It is now clear that cross resistance is a potential issue between various treatments, especially those agents that target the androgen axis. This review highlights the need for additional studies to optimize the current treatments for these patients.

  2. Prostatic adenocarcinoma with mandibular metastatic lesion: case report.

    Science.gov (United States)

    Reyes Court, Daniel; Encina, Susana; Levy, Irene

    2007-10-01

    Metastatic lesions of primary tumors, which originate in different parts of the body, comprise almost 1 % of different types of oral cancers. These lesions can affect either bones or soft tissues in the maxillofacial region. Whenever the maxillofacial area is affected, the most common location is in the molar region of the mandible. The clinical presentation of mandibular metastasis follows a clinical pattern characterized by irradiated dental pain in the third molar region. The most frequent sign is parethesia of the area innervated by the mandibular alveolar dental nerve. Differential diagnosis and treatment of these patients can be extremely difficult because there a number of pathologic conditions with similar symptoms and because diagnostic examination can be highly confusing. The aim of this article is to present a case of prostatic adenocarcinoma where the only metastasis was found in the jaw. A literature review will be presented, hoping to contribute to the scarce information regarding this lesion, due to its low frequency and atypical expression of this type of metastasis in terms of etiology, biological behavior and treatment.

  3. SU-D-303-01: Spatial Distribution of Bone Metastases In Metastatic Castrate-Resistant Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Perk, T; Bradshaw, T; Harmon, S; Perlman, S; Liu, G; Jeraj, R [University of Wisconsin, Madison, WI (United States)

    2015-06-15

    Purpose: Identification of metastatic bone lesions is critical in prostate cancer, where treatments may be more effective in patients with fewer lesions. This study aims characterize the distribution and spread of bone lesions and create a probability map of metastatic spread in bone. Methods: Fifty-five metastatic castrate-resistant prostate cancer patients received up to 3 whole-body [F-18]NaF PET/CT scans. Lesions were identified by physician on PET/CT and contoured using a threshold of SUV>15. An atlas-based segmentation method was used to create CT regions, which determined skeletal location of lesions. Patients were divided into 3 groups with low (N<40), medium (40100) numbers of lesions. A combination of articulated and deformable registrations was used to register the skeletal segments and lesions of each patient to a single skeleton. All the lesion data was then combined to make a probability map. Results: A total of 4038 metastatic lesions (mean 74, range 2–304) were identified. Skeletal regions with highest occurrence of lesions included ribs, thoracic spine, and pelvis with 21%, 19%, and 15% of the total number lesions and 8%, 18%, and 31 % of the total lesion volume, respectively. Interestingly, patients with fewer lesions were found to have a lower proportion of lesions in the ribs (9% in low vs. 27% in high number of lesions). Additionally, the probability map showed specific areas in the spine and pelvis where over 75% of patients had metastases, and other areas in the skeleton with a less than 2% of metastases. Conclusion: We identified skeletal regions with higher incidence of metastases and specific sub-regions in the skeleton that had high or low probability of occurrence of metastases. Additionally, we found that metastatic lesions in the ribs and skull occur more commonly in advanced disease. These results may have future applications in computer-aided diagnosis. Funding from the Prostate Cancer Foundation.

  4. Is there a role for antiandrogen monotherapy in patients with metastatic prostate cancer?

    DEFF Research Database (Denmark)

    Kaisary, A V; Iversen, P; Tyrrell, C J;

    2001-01-01

    with a prostate specific antigen (PSA) level 400 ng/ml) may decide that quality of life and symptomatic benefits outweigh the slight survival disadvantage seen in clinical trials and opt for bicalutamide monotherapy as an alternative to castration.Prostate Cancer and Prostatic Diseases (2001) 4, 196-203.......Castration is the most widely used form of androgen ablation employed in the treatment of metastatic (M1) prostate cancer. Non-steroidal antiandrogen monotherapy is a potential alternative treatment option for men for whom castration is unacceptable or not indicated. Of the three non...

  5. Update on options for treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Prakash Vishnu

    2010-03-01

    Full Text Available Prakash Vishnu, Winston W TanDivision of Hematology Oncology, Mayo Clinic, Jacksonville, FL, USABackground: Prostate cancer is one of the most common cancers in men in US and European countries. Despite having a favorable prognosis, the incidence of incurable metastatic disease and mortality in the US is about 28,000 per year. Although hormone-based androgen deprivation therapies typically result in rapid responses, nearly all patients eventually develop progressive castration-resistant disease state. With readily available prostate-specific antigen (PSA testing, most of these patients are asymptomatic and manifest progression simply as a rising PSA. In patients with castration-resistant prostate cancer (CRPC, the median survival is about 1–2 years, with improvements in survival seen mostly with docetaxel-based regimens. The purpose of this article is to review the recent developments in the treatment of advanced CRPC.Recent findings: Since the two landmark trials (TAX-327 and Southwest Oncology Group 99–16 in CRPC, several newer cytotoxic drugs (epothilones, satraplatin, targeted agents (abiraterone, MDV3100 and vaccines have been tested in phase II and III setting with promising results.Conclusions: The role of newer agents in the treatment of CRPC still needs to be validated by phase III trials, which are currently ongoing. Whilst the novel biomarkers, ‘circulating tumor cells’, have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making, their exact utility and relevance calls for a larger prospective validation.Keywords: castration-resistant prostate cancer, novel therapies, mechanisms of resistance, circulating tumor cells

  6. Navigating the evolving therapeutic landscape in advanced prostate cancer.

    Science.gov (United States)

    Crawford, E David; Petrylak, Daniel; Sartor, Oliver

    2017-03-07

    Prostate cancer is the most common cause of cancer in men, with 137.9 new cases per 100,000 men per year. The overall 5-year survival rate for prostate cancer is very high. Up to 20% of men who undergo state-of-the art treatment for prostate cancer will develop castration-resistant prostate cancer (CRPC) within 5 years, with median survival for those with metastatic CRPC ranging from approximately 15 to 36 months in recent studies. With the advent of several new drugs in the past 5 years to treat CRPC, the challenge facing clinicians is how to best sequence or combine therapies or both to optimize outcomes. A better understanding of the disease process and the role of the androgen receptor as a target for both therapy and resistance have led to the consideration of biomarkers as an approach to aid in selecting the appropriate agent for a given patient as patients respond to or tolerate different drugs differently. Research to identify new prognostic biomarkers, which are associated with outcome measures, as well as predictive biomarkers, which predict response or resistance to therapy is ongoing. The treatment of advanced prostate cancer and the research related to biomarkers are discussed.

  7. A Comprehensive Review of Contemporary Role of Local Treatment of the Primary Tumor and/or the Metastases in Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Fouad Aoun

    2014-01-01

    Full Text Available To provide an overview of the currently available literature regarding local control of primary tumor and oligometastases in metastatic prostate cancer and salvage lymph node dissection of clinical lymph node relapse after curative treatment of prostate cancer. Evidence Acquisition. A systematic literature search was conducted in 2014 to identify abstracts, original articles, review articles, research articles, and editorials relevant to the local control in metastatic prostate cancer. Evidence Synthesis. Local control of primary tumor in metastatic prostate cancer remains experimental with low level of evidence. The concept is supported by a growing body of genetic and molecular research as well as analogy with other cancers. There is only one retrospective observational population based study showing prolonged survival. To eradicate oligometastases, several options exist with excellent local control rates. Stereotactic body radiotherapy is safe, well tolerated, and efficacious treatment for lymph node and bone lesions. Both biochemical and clinical progression are slowed down with a median time to initiate ADT of 2 years. Salvage lymph node dissection is feasible in patients with clinical lymph node relapse after local curable treatment. Conclusion. Despite encouraging oncologic midterm results, a complete cure remains elusive in metastatic prostate cancer patients. Further advances in imaging are crucial in order to rapidly evolve beyond the proof of concept.

  8. Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma

    DEFF Research Database (Denmark)

    Brasso, Klaus; Christensen, Ib Jarle; Johansen, Julia S;

    2006-01-01

    To examine the prognostic value of markers of bone metabolism (serum PINP, BAP, and CTX-I) and serum YKL-40 in metastatic prostate carcinoma (PC).......To examine the prognostic value of markers of bone metabolism (serum PINP, BAP, and CTX-I) and serum YKL-40 in metastatic prostate carcinoma (PC)....

  9. Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy

    DEFF Research Database (Denmark)

    Sternberg, Cora N; Castellano, Daniel; Daugaard, Gedske

    2014-01-01

    BACKGROUND: In the final analysis of the phase 3 COU-AA-301 study, abiraterone acetate plus prednisone significantly prolonged overall survival compared with prednisone alone in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. Here, we present the final...... analysis of an early-access protocol trial that was initiated after completion of COU-AA-301 to enable worldwide preapproval access to abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy. METHODS: We did a multicentre, open-label, early......-access protocol trial in 23 countries. We enrolled patients who had metastatic castration-resistant prostate cancer progressing after taxane chemotherapy. Participants received oral doses of abiraterone acetate (1000 mg daily) and prednisone (5 mg twice a day) in 28-day cycles until disease progression...

  10. Cabazitaxel: more than a new taxane for metastatic castrate-resistant prostate cancer?

    Science.gov (United States)

    Mita, Alain C; Figlin, Robert; Mita, Monica M

    2012-12-15

    The taxanes are recognized as a major class of chemotherapeutic agents; however, mechanisms of innate and acquired resistance can limit their usefulness. Cabazitaxel, a novel taxane with microtubule-stabilizing potency similar to docetaxel, exhibits activity against tumor cell lines resistant to paclitaxel and docetaxel. Cabazitaxel showed linear pharmacokinetics and a terminal elimination half-life comparable with that of docetaxel, findings which support dosing as a single infusion in three-week treatment cycles. Dose-ranging studies recommended doses of 20 or 25 mg/m(2) every three weeks. Antitumor activity was shown in patients with advanced cancer and chemotherapy failure (including taxane failure). Other early studies investigated the efficacy of cabazitaxel in pretreated metastatic breast cancer, either as a single agent or in combination with capecitabine. Objective antitumor response rates of up to 24% and sustained tumor stabilizations were also observed. The TROPIC phase III study, conducted in patients with metastatic castrate-resistant prostate cancer previously treated with docetaxel, established cabazitaxel as the first chemotherapeutic agent to offer a survival advantage in this patient population. Across these studies, the dose-limiting hematologic toxicity was neutropenia (including febrile neutropenia), usually controllable with colony-stimulating factor/granulocyte-colony stimulating factor support.

  11. Clinical use of abiraterone in the treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Zobniw CM

    2014-08-01

    Full Text Available Chrystia M Zobniw,1 Alanna Causebrook,2 Mei Ka Fong1 1Department of Pharmacy, Roswell Park Cancer Institute, Buffalo, NY, USA; 2School of Pharmacy, Lake Erie College of Osteopathic Medicine, Erie, PA, USA Abstract: Prostate cancer remains the most common type of cancer among men in the United States. Treatment for metastatic prostate cancer has improved significantly over the years with more and more agents improving overall survival. This review will address the pathophysiology of prostate cancer followed by the mechanism of action and the pharmacokinetic properties of abiraterone. The review will also discuss the role of abiraterone in the treatment of metastatic castrate-resistant prostate cancer. Keywords: glucocorticoid receptor, CYP17, pipeline, enzalutamide, sipuleucel-T, drug resistance, radium-223 dichloride

  12. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    Science.gov (United States)

    2014-09-01

    effects due to the loss of testosterone (including fatigue, decreased sexual desire, weight gain, loss of muscle mass and osteoporosis ) and the well...beyond the prostate, immunotherapy may be the only way to treat it [6, 7]. A majority of clinical trials for the immunotherapy of prostate cancer...Localized Prostate Cancer. J Sex Med, 2012. 5. Fitzpatrick, J.M., Management of localized prostate cancer in senior adults : the crucial role of comorbidity

  13. Neural Cell Adhesion Protein CNTN1 Promotes the Metastatic Progression of Prostate Cancer.

    Science.gov (United States)

    Yan, Judy; Ojo, Diane; Kapoor, Anil; Lin, Xiaozeng; Pinthus, Jehonathan H; Aziz, Tariq; Bismar, Tarek A; Wei, Fengxiang; Wong, Nicholas; De Melo, Jason; Cutz, Jean-Claude; Major, Pierre; Wood, Geoffrey; Peng, Hao; Tang, Damu

    2016-03-15

    Prostate cancer metastasis is the main cause of disease-related mortality. Elucidating the mechanisms underlying prostate cancer metastasis is critical for effective therapeutic intervention. In this study, we performed gene-expression profiling of prostate cancer stem-like cells (PCSC) derived from DU145 human prostate cancer cells to identify factors involved in metastatic progression. Our studies revealed contactin 1 (CNTN1), a neural cell adhesion protein, to be a prostate cancer-promoting factor. CNTN1 knockdown reduced PCSC-mediated tumor initiation, whereas CNTN1 overexpression enhanced prostate cancer cell invasion in vitro and promoted xenograft tumor formation and lung metastasis in vivo. In addition, CNTN1 overexpression in DU145 cells and corresponding xenograft tumors resulted in elevated AKT activation and reduced E-cadherin (CDH1) expression. CNTN1 expression was not readily detected in normal prostate glands, but was clearly evident on prostate cancer cells in primary tumors and lymph node and bone metastases. Tumors from 637 patients expressing CNTN1 were associated with prostate cancer progression and worse biochemical recurrence-free survival following radical prostatectomy (P prostate cancer progression and metastasis, prompting further investigation into the mechanisms that enable neural proteins to become aberrantly expressed in non-neural malignancies.

  14. Abiraterone plus prednisone improves survival in metastatic castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Scott T Tagawa; Himisha Beltran

    2011-01-01

    In essentially just 1 year's time,we have seen science translated into exciting new therapeutic agents for men with metastatic castration-resistant prostate cancer (CRPC),1 most recently with the United States Food and Drug Administration (FDA) approval of abiraterone acetate in combination with prednisone.2 While prostate cancer has been known to be highly responsive to surgical or medical castration for well over half a century,3 what was once termed 'hormone refractory' prostate cancer inevitably developed,leading to cancerrelated death.Many consider the introduction of chemotherapy for CRPC initially for symptomatic benefit,then with improvements in survival,a substantial step forward.

  15. Prostate carcinoma metastatic to the skin as an extrammamary Paget’s disease

    Directory of Open Access Journals (Sweden)

    Petcu Eugen

    2012-08-01

    Full Text Available Abstract Aim The current paper describes a case of prostatic adenocarcinoma metastatic to the skin presenting as an extrammamary Paget's disease, a very rare and poorly characterised morphological entity. We report a case of prostatic carcinoma metastatic to skin showing a pattern of extramammary Paget's disease which has not been clearly illustrated in the literature Case presentation: A 63 year-old man with prostatic adenocarcinoma developed cutaneous metastases after 16 years. The inguinal metastases were sessile and 'keratotic.' The tumour displayed solid, glandular areas as well as a polypoid region suggestive of extramammary Paget's disease were identified. Discussion and conclusions We review the diagnostic criteria that have led to the correct histopathological diagnosis in this case. A differential diagnosis of the pagetoid spread in the skin and various forms of cutaneous metastases determined by a prostatic adenocarcinoma as well as the role of immunohistochemistry in establishing the prostatic origin are presented in the context of this case. Although, morphologically the cells presented in the skin deposits were not characteristic for adenocarcinoma of prostate, immunohistochemistry for PSA and PSAP suggested a prostatic origin. Virtual Slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1395450057455276

  16. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana;

    2017-01-01

    Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated...

  17. Docetaxel rechallenge after an initial good response in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Oudard, Stéphane; Kramer, Gero; Caffo, Orazio

    2015-01-01

    OBJECTIVE: To evaluate the benefit of docetaxel rechallenge in patients with metastatic castration-resistant prostate cancer (mCRPC) relapsing after an initial good response to first-line docetaxel. PATIENTS AND METHODS: We retrospectively reviewed the records of consecutive patients with mCRPC w...

  18. Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Heidenreich, Axel; Bracarda, Sergio; Mason, Malcolm;

    2014-01-01

    BACKGROUND: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access progra...

  19. Abiraterone in the treatment of metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Mostaghel EA

    2014-01-01

    Full Text Available Elahe A Mostaghel Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA, USA Abstract: Androgen deprivation therapy remains the single most effective treatment for the initial therapy of advanced prostate cancer, but is uniformly marked by progression to castration-resistant prostate cancer (CRPC. Residual tumor androgens and androgen axis activation are now recognized to play a prominent role in mediating CRPC progression. Despite suppression of circulating testosterone to castrate levels, castration does not eliminate androgens from the prostate tumor microenvironment and residual androgen levels are well within the range capable of activating the androgen receptor (AR and AR-mediated gene expression. Accordingly, therapeutic strategies that more effectively target production of intratumoral androgens are necessary. The introduction of abiraterone, a potent suppressor of cytochrome P450 17 α-hydroxysteroid dehydrogenase-mediated androgen production, has heralded a new era in the hormonal treatment of men with metastatic CRPC. Herein, the androgen and AR-mediated mechanisms that contribute to CRPC progression and establish cytochrome P450 17 α-hydroxysteroid dehydrogenase as a critical therapeutic target are briefly reviewed. The mechanism of action and pharmacokinetics of abiraterone are reviewed and its recently described activity against AR and 3-β-hydroxysteroid dehydrogenase is discussed. The Phase I and II data initially demonstrating the efficacy of abiraterone and Phase III data supporting its approval for patients with metastatic CRPC are reviewed. The safety and tolerability of abiraterone, including the incidence and management of side effects and potential drug interactions, are discussed. The current place of abiraterone in CRPC therapy is reviewed and early evidence regarding cross-resistance of abiraterone with taxane therapy, mechanisms of resistance to abiraterone, and observations of an

  20. Management of patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Gillessen, S; Omlin, A; Attard, G

    2015-01-01

    -resistant prostate cancer and the recent studies of chemo-hormonal therapy in men with castration-naïve prostate cancer have led to considerable uncertainty as to the best treatment choices, sequence of treatment options and appropriate patient selection. Management recommendations based on expert opinion......The first St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) Expert Panel identified and reviewed the available evidence for the ten most important areas of controversy in advanced prostate cancer (APC) management. The successful registration of several drugs for castration...... decisions on treatment as always will involve consideration of disease extent and location, prior treatments, host factors, patient preferences as well as logistical and economic constraints. Inclusion of men with APC in clinical trials should be encouraged....

  1. Vismodegib: in locally advanced or metastatic basal cell carcinoma.

    Science.gov (United States)

    Keating, Gillian M

    2012-07-30

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the US, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. Vismodegib selectively and potently inhibits the Hedgehog signalling pathway by binding to Smoothened, thereby inhibiting the activation of Hedgehog target genes. Oral vismodegib was effective in the treatment of patients with locally advanced (n = 63) or metastatic (n = 33) BCC, according to the results of an ongoing, noncomparative, multinational, pivotal, phase II trial (ERIVANCE BCC). In this trial (using a clinical cutoff date of 26 November 2010), the independent review facility overall response rate was 42.9% in patients with locally advanced BCC and 30.3% in patients with metastatic BCC. In both patients with locally advanced BCC and those with metastatic BCC, the median duration of response was 7.6 months and median progression-free survival was 9.5 months. Oral vismodegib had an acceptable tolerability profile in patients with advanced BCC.

  2. Cyclin-dependent kinase 5 activity controls cell motility and metastatic potential of prostate cancer cells.

    Science.gov (United States)

    Strock, Christopher J; Park, Jong-In; Nakakura, Eric K; Bova, G Steven; Isaacs, John T; Ball, Douglas W; Nelkin, Barry D

    2006-08-01

    We show here that cyclin-dependent kinase 5 (CDK5), a known regulator of migration in neuronal development, plays an important role in prostate cancer motility and metastasis. P35, an activator of CDK5 that is indicative of its activity, is expressed in a panel of human and rat prostate cancer cell lines, and is also expressed in 87.5% of the human metastatic prostate cancers we examined. Blocking of CDK5 activity with a dominant-negative CDK5 construct, small interfering RNA, or roscovitine resulted in changes in the microtubule cytoskeleton, loss of cellular polarity, and loss of motility. Expression of a dominant-negative CDK5 in the highly metastatic Dunning AT6.3 prostate cancer cell line also greatly impaired invasive capacity. CDK5 activity was important for spontaneous metastasis in vivo; xenografts of AT6.3 cells expressing dominant-negative CDK5 had less than one-fourth the number of lung metastases exhibited by AT6.3 cells expressing the empty vector. These results show that CDK5 activity controls cell motility and metastatic potential in prostate cancer.

  3. Novel tracers and their development for the imaging of metastatic prostate cancer.

    Science.gov (United States)

    Apolo, Andrea B; Pandit-Taskar, Neeta; Morris, Michael J

    2008-12-01

    There are presently no accurate methods of imaging prostate cancer metastases to bone. An unprecedented number of novel imaging agents, based on the biology of the disease, are now available for testing. We reviewed contemporary molecular imaging modalities that have been tested in humans with metastatic prostate cancer, with consideration of the studies' adherence to current prostate cancer clinical trial designs. Articles from the years 2002 to 2008 on PET using (18)F-FDG, (11)C-choline, (18)F-choline, (18)F-flouride, (11)C-acetate, (11)C-methionine, and (18)F-fluoro-5alpha-dihydrotestosterone in patients with metastatic prostate cancer were reviewed. Although these studies are encouraging, most focus on the rising population with prostate-specific antigen, and many involve small numbers of patients and do not adhere to consensus criteria for clinical trial designs in prostate cancer. Hence, although many promising agents are available for testing, such studies would benefit from closer collaboration between those in the fields of medical oncology and nuclear medicine.

  4. Immunohistochemical profiles of claudin-3 in primary and metastatic prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Becich Michael J

    2011-01-01

    Full Text Available Abstract Background Claudins are integral membrane proteins that are involved in forming cellular tight junctions. One member of the claudin family, claudin-3, has been shown to be overexpressed in breast, ovarian, and pancreatic cancer. Here we use immunohistochemistry to evaluate its expression in benign prostatic hyperplasia (BPH, prostatic intraepithelial neoplasia (PIN, normal tissue adjacent to prostatic adenocarcinoma (NAC, primary prostatic adenocarcinoma (PCa, and metastatic prostatic adenocarcinoma (Mets. Methods Tissue microarrays were immunohistochemically stained for claudin-3, with the staining intensities subsequently quantified and statistically analyzed using a one-way ANOVA with subsequent Tukey tests for multiple comparisons or a nonparametric equivalent. Fifty-three cases of NAC, 17 cases of BPH, 35 cases of PIN, 107 cases of PCa, and 55 cases of Mets were analyzed in the microarrays. Results PCa and Mets had the highest absolute staining for claudin-3. Both had significantly higher staining than BPH (p Conclusions To our knowledge, this represents one of the first studies comparing the immunohistochemical profiles of claudin-3 in PCa and NAC to specimens of PIN, BPH, and Mets. These findings provide further evidence that claudin-3 may serve as an important biomarker for prostate cancer, both primary and metastatic, but does not provide evidence that claudin-3 can be used to predict risk of metastasis.

  5. Treatment of locally advanced prostatic cancer

    Directory of Open Access Journals (Sweden)

    Marušić Goran

    2010-01-01

    Full Text Available Introduction. A locally advanced prostate cancer is defined as a malignant process spreading beyond the prostate capsule or in seminal vesicles but without distant metastasis or regional lymph nodes invasion. Clinical classification, prediction and treatment of prostate cancer. An exact staging of clinical T3 stadium is usually difficult because of the frequent over and under staging. The risk prognostic stratification is performed through nomograms and ANN (artificial neural networks. The options for treatment are: radical prostatectomy, external radiotherapy and interstitial implantation of radioisotopes, hormonal therapy by androgen blockade. Radical prostatectomy is considered in patients with T3 stage but extensive dissection of lymph nodes, dissection of neurovascular bundle (on tumor side, total removal of seminal vesicle and sometimes resection of bladder neck are obligatory. Postoperative radiotherapy is performed in patients with invasion of seminal vesicles and capsular penetration or with prostate specific antigen value over 0.1 ng/ml, one month after the surgical treatment. Definitive radiotherapy could be used as the best treatment option considering clinical stage, Gleason score, age, starting prostate specific antigen (PSA value, concomitant diseases, life expectancy, quality of life, through multidisciplinary approach (combined with androgen deprivation. Hormonal therapy in intended for patients who are not eligible for surgical treatment or radiotherapy. Conclusion. Management of locally advanced prostate cancer is still controversial and studies for better diagnosis and new treatment modalities are ongoing.

  6. Metastatic prostatic adenocarcinoma diagnosed in a bronchoalveolar lavage specimen: An unusual presentation of a common tumor

    Directory of Open Access Journals (Sweden)

    Adrienne E Moul

    2016-01-01

    Full Text Available Metastatic prostatic adenocarcinoma presenting as a primary lung disease is rare. We present a 52-year-old male with a 3-month history of cough, shortness of breath, and weight loss with clinical and radiological findings suggestive of a primary lung disease: Bilateral interstitial and alveolar opacities with blunting of the costophrenic angles, multiple diffuse foci of consolidations and nodules, predominantly subpleural and located in the lower lobes, and diffuse interlobular septal thickening and peribronchial thickening. The patient underwent bronchoscopy and bronchoalveolar lavage (BAL was obtained. Cytospin smears were diagnostic for a low-grade adenocarcinoma. Clinically, the patient had elevated serum prostate-specific antigen (PSA levels greater than 5,000 ng/mL. Because of this, immunocytochemistry for PSA was performed which was positive, confirming the diagnosis of metastatic prostatic adenocarcinoma. This unusual case of metastatic adenocarcinoma of the prostate first diagnosed by BAL highlights the significance of available clinical information and the use of immunocytochemistry for proper diagnosis.

  7. Management of locally advanced prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Heather Payne

    2009-01-01

    The management of all stages of prostate cancer is an increasingly complex process and involves a variety of available treatments and many disciplines.Despite prostate-specific antigen (PSA) testing,the presentation of prostate cancer at a locally advanced stage is common in the UK,accounting for one-third of all new cases.There is no universally accepted definition of locally advanced prostate cancer;the term is loosely used to encompass a spectrum of disease profiles that show high-risk features.Men with high-risk prostate cancer generally have a significant risk of disease progression and cancer-related death if left untreated.High-risk patients,including those with locally advanced disease,present two specific challenges.There is a need for local control as well as a need to treat any microscopic metastases likely to be present but undetectable until disease progression.The optimal treatment approach will therefore often necessitate multiple modalities.The exact combinations,timing and intensity of treatment continue to be strongly debated.Management decisions should be made after all treatments have been discussed by a multidisciplinary team (including urologists,oncologists,radiologists,pathologists and nurse specialists) and after the balance of benefits and side effects of each therapy modality has been considered by the patient with regard to his own individual circumstances.This article reviews the current therapy options.

  8. Sipuleucel-T for the treatment of metastatic prostate cancer: promise and challenges.

    Science.gov (United States)

    Paller, Channing J; Antonarakis, Emmanuel S

    2012-04-01

    In the past 18 mo, three new life-prolonging therapies have been approved by the US. Food and Drug Administration for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC), including sipuleucel-T, the first therapeutic vaccine approved for this disease. With very low toxicity and a demonstrable overall survival benefit, sipuleucel-T offers a promising new therapy and validates further investigation into other immunotherapy approaches for prostate cancer patients. However, questions about its mechanism of action, concerns about its cost, and its optimal sequencing in the prostate cancer treatment landscape may be limiting the adoption of sipuleucel-T. This review summarizes the state-of-the-science with respect to immunotherapy approaches for men with prostate cancer, provides information about the clinical development as well as the strengths and concerns associated with sipuleucel-T, and offers initial insights about where this promising treatment may best fit in the therapeutic landscape.

  9. Evolving treatment approaches for the management of metastatic castration-resistant prostate cancer – role of radium-223

    Directory of Open Access Journals (Sweden)

    Mukherji D

    2014-05-01

    Full Text Available Deborah Mukherji,1 Imane El Dika,1 Sally Temraz,1 Mohammed Haidar,2 Ali Shamseddine11Department of Hematology/Oncology, 2Department of Nuclear Medicine, American University of Beirut Medical Center, Beirut, LebanonAbstract: Radium-223 is a first-in-class alpha particle-emitting radiopharmaceutical approved for the treatment of bone metastatic castration-resistant prostate cancer. Radium-223 is administered intravenously with no requirement for complex shielding and specifically targets areas of bone metastasis. In a randomized placebo-controlled Phase III study, treatment with radium-223 was shown to improve overall survival, time to skeletal-related events, and health-related quality of life. Apart from radium-223, the cytotoxic chemotherapy agents docetaxel and cabazitaxel, androgen biosynthesis inhibitor abiraterone acetate, novel anti-androgen enzalutamide, and immunotherapy sipuleucel-T have also been shown to improve survival of men with advanced prostate cancer in Phase III trials. This review will outline current treatment approaches for advanced prostate cancer with a focus on the role of radium-223 in changing treatment paradigms.Keywords: Alpharadin, alpha-emitting radionuclide, bone metastasis

  10. Role of Chemotherapy and Mechanisms of Resistance to Chemotherapy in Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    Lohiya, Vipin; Aragon-Ching, Jeanny B.; Sonpavde, Guru

    2016-01-01

    Chemotherapy using the taxanes, docetaxel and cabazitaxel, remains an important therapeutic option in metastatic castration-resistant prostate cancer (CRPC). However, despite the survival benefits afforded by these agents, the survival increments are modest and resistance occurs universally. Efforts to overcome resistance to docetaxel by combining with biologic agents have heretofore been unsuccessful. Indeed, resistance to these taxanes is also associated with cross-resistance to the antiandrogen drugs, abiraterone and enzalutamide. Here, we discuss the various mechanisms of resistance to chemotherapy in metastatic CRPC and the potential role of emerging regimens and agents in varying clinical phases of development.

  11. Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma

    DEFF Research Database (Denmark)

    Brasso, Klaus; Christensen, Ib Jarle; Johansen, Julia S.;

    2006-01-01

    BACKGROUND: To examine the prognostic value of markers of bone metabolism (serum PINP, BAP, and CTX-I) and serum YKL-40 in metastatic prostate carcinoma (PC). METHODS: The biomarkers were determined by ELISAs in 153 metastatic PC patients before treatment with parenteral estrogen or total androgen...

  12. Diagnostic utility of p501s (prostein in comparison to prostate specific antigen (PSA for the detection of metastatic prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Parwani Anil V

    2007-10-01

    Full Text Available Abstract Background Immunohistochemical detection of prostate specific antigen (PSA is widely used to identify metastatic prostatic adenocarcinoma. However, PSA may not be expressed in some poorly differentiated prostatic carcinomas and its immunoreactivity has been found in some non-prostatic tissues. P501s (prostein is a prostate-specific marker that is expressed in the cytoplasm of benign and malignant prostatic glandular cells. It has not been detected in any other normal or malignant tissues. The purpose of this study was to evaluate the expression of P501s in metastatic prostatic adenocarcinoma and compare its expression with PSA. Methods Immunohistochemical stains with anti-P501s antibodies were performed on 5-micron sections of tissue microarray (TMA specimens. The TMA is constructed with normal donor prostates (NDP, prostatic adenocarcinoma (PRCA, non-neoplastic prostatic tissues adjacent to malignant glands (NAT, benign prostatic hyperplasia (BPH, high-grade prostatic neoplasia (PIN, metastatic adenocarcinoma to lymph nodes (MLN, metastatic adenocarcinoma to other sites (MC, and samples of benign testis, colon, adrenal and kidney. The two groups of metastatic lesions were also subjected to stains with antibodies to PSA. A composite score (ranging from 0 to 3 was assigned to score intensity of staining. Results Granular staining pattern of p501s was seen in all benign glands (score = 1.77 – 2.1 and malignant acini (score = 1.52 at the apical aspect of cytoplasm, predominantly adjacent to the nuclei. No staining was observed in controls including testis, colon, adrenal and kidney. The MLN group received a score of 1.0, with 10% of cases negative for p501s. The MC cases had a score of 0.64, with 16.7% of case showing loss of p501s expression. Although the metastatic lesions demonstrated similar rate of negative expression with PSA antibody, only 2 MC cases (3.3% showed simultaneous negative stains for both P501S and PSA. Conclusion P501

  13. Cabazitaxel:a new drug for metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Marijo Bilusic; William L Dahut

    2011-01-01

    @@ In Western countries, prostate cancer is the most common malignancy in men and ranks third in mortality.In 2010, an esti-mated 217 730 new cases are anticipated in the United States, and about 32 050 men are expected to die from the disease.

  14. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    Science.gov (United States)

    2013-09-01

    overcome the suppressive activity of regulatory T cells while simultaneously inducing prostate cancer-specific immunity. LIGHT, a ligand for Herpes ...altering the tumor microenvironment by increasing NOS expression and compromising tumor immunosuppression via Tregs. REPORTABLE OUTCOMES 1. Oral ...13 APPENDICES Yan, Lisa Southern California Clinical and Translational Science Institute Oral Presentation- May 6, 2013 Forced LIGHT

  15. How MMPs Impact Bone Responses to Metastatic Prostate Cancer

    Science.gov (United States)

    2011-04-30

    metastatic bone cancer: consensus recommendations from the Second Cambridge Conference. Clin Cancer Res 2008; 14: 6387-95. 10. Cackowski FC, Roodman GD...2005;184:1266–73. 20. Cackowski FC, Roodman GD. Perspective on the osteoclast: an an- giogenic cell? Ann N Y Acad Sci 2007;1117:12–25. 21. Bergers G...We are grateful to Kevin P. Weller and David K. Flaherty for their assistance with flow cytometry. Flow cytometry experiments were performed in the

  16. Acute Respiratory Distress Syndrome after Treatment of Metastatic Prostate Cancer with Taxotere: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Ali Raufi

    2015-01-01

    Full Text Available Prostate cancer is the most common cancer in men. Docetaxel is a common chemotherapeutic agent that has proven its efficacy in the treatment of patients with both castration sensitive and resistant metastatic prostate cancer. We report a case of acute respiratory distress syndrome (ARDS in a patient with metastatic prostate cancer treated with docetaxel (Taxotere. ARDS is very rare but life threatening complication of docetaxel which requires aggressive supportive care and close monitoring. Better awareness and prompt diagnosis of this treatment related ARDS will improve the effectiveness and outcome of its management.

  17. Cabazitaxel as second-line or third-line therapy in patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge M; Lindberg, Henriette

    2016-01-01

    To compare treatment outcomes in patients with metastatic castration-resistant prostate cancer treated with cabazitaxel (CA) as second-line or third-line therapy in the everyday clinical setting. Charts from 94 patients treated with CA as second-line (n=28) or third-line therapy (n=66) were...... evaluated. Common Terminology Criteria for Adverse Events were used to register grade 3-4 nonhematological toxicity during treatment with CA. Baseline metastatic castration-resistant prostate cancer-related prognostic factors, duration of therapy, and maximum prostate-specific antigen (PSA) percentage...

  18. PrognosticValue of PINP,BoneAlkaline Phosphatase, CTX-I, andYKL-40 in Patients With Metastatic Prostate Carcinoma

    DEFF Research Database (Denmark)

    Brasso, Klaus; Christensen, Ib Jarle; Johansen, Julia S

    2006-01-01

    Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006 Apr 1;66(5):503-13. PMID: 16372331 [PubMed - indexed for MEDLINE]......Prognostic value of PINP, bone alkaline phosphatase, CTX-I, and YKL-40 in patients with metastatic prostate carcinoma. Prostate. 2006 Apr 1;66(5):503-13. PMID: 16372331 [PubMed - indexed for MEDLINE]...

  19. LIGHT: A Novel Immunotherapy for Primary and Metastatic Prostate Cancer

    Science.gov (United States)

    2012-09-01

    Membrane bound LIGHT was detected via flow cytometry with LTR-Fc antibody . Expression of LIGHT correlates with the mRNA expression level, where 24 hours...prostate cancer but their regulatory T cells may be depleted via administration of diphtheria toxin. The advantage of using this transgenic mouse...Tumors were homogenized and supernatant was collected for a multiplex ELISA , Bioplex Assay (Figure 4). The following cytokines/chemokines were analyzed

  20. Vascular Differences Detected by MRI for Metastatic Versus Nonmetastatic Breast and Prostate Cancer Xenografts

    Directory of Open Access Journals (Sweden)

    Zaver M. Bhujwalla

    2001-01-01

    Full Text Available Several studies have linked vascular density, identified in histologic sections, to “metastatic risk.” Functional information of the vasculature, not readily available from histologic sections, can be obtained with contrast-enhanced MRI to exploit for therapy or metastasis prevention. Our aims were to determine if human breast and prostate cancer xenograffs preselected for differences in invasive and metastatic characteristics established correspondingly different vascular volume and permeability, quantified here with noninvasive MRI of the intravascular contrast agent albumin-GdDTPA. Tumor vascular volume and permeability of human breast and prostate cancer xenografts were characterized using MRI. Parallel studies confirmed the invasive behavior of these cell lines. Vascular endothelial growth factor (VEGF expression in the cell lines was measured using ELISA and Western blots. Metastasis to the lungs was evaluated with spontaneous as well as experimental assay. Metastatic tumors formed vasculature with significantly higher permeability or vascular volume (P < .05, two-sided unpaired t test. The permeability profile matched VEGF expression. Within tumors, regions of high vascular volume usually exhibited low permeability whereas regions of low vascular volume exhibited high permeability. We observed that although invasion was necessary, without adequate vascularization it was not sufficient for metastasis to occur.

  1. Fluid biopsy in patients with metastatic prostate, pancreatic and breast cancers

    Science.gov (United States)

    Marrinucci, Dena; Bethel, Kelly; Kolatkar, Anand; Luttgen, Madelyn S.; Malchiodi, Michael; Baehring, Franziska; Voigt, Katharina; Lazar, Daniel; Nieva, Jorge; Bazhenova, Lyudmila; Ko, Andrew H.; Korn, W. Michael; Schram, Ethan; Coward, Michael; Yang, Xing; Metzner, Thomas; Lamy, Rachelle; Honnatti, Meghana; Yoshioka, Craig; Kunken, Joshua; Petrova, Yelena; Sok, Devin; Nelson, David; Kuhn, Peter

    2012-02-01

    Hematologic spread of carcinoma results in incurable metastasis; yet, the basic characteristics and travel mechanisms of cancer cells in the bloodstream are unknown. We have established a fluid phase biopsy approach that identifies circulating tumor cells (CTCs) without using surface protein-based enrichment and presents them in sufficiently high definition (HD) to satisfy diagnostic pathology image quality requirements. This 'HD-CTC' assay finds >5 HD-CTCs mL-1 of blood in 80% of patients with metastatic prostate cancer (n = 20), in 70% of patients with metastatic breast cancer (n = 30), in 50% of patients with metastatic pancreatic cancer (n = 18), and in 0% of normal controls (n = 15). Additionally, it finds HD-CTC clusters ranging from 2 HD-CTCs to greater than 30 HD-CTCs in the majority of these cancer patients. This initial validation of an enrichment-free assay demonstrates our ability to identify significant numbers of HD-CTCs in a majority of patients with prostate, breast and pancreatic cancers.

  2. Clinical appraisal of abiraterone in the treatment of metastatic prostatic cancer: patient considerations, novel opportunities, and future directions

    Directory of Open Access Journals (Sweden)

    Mitsiades N

    2013-01-01

    Full Text Available Diego J Bedoya,1 Nicholas Mitsiades2,31Clearview Cancer Institute, Huntsville, AL, USA; 2Department of Medicine, 3Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USAAbstract: While androgen-deprivation therapy can induce dramatic clinical responses in advanced and metastatic prostate cancer, refractory disease (castration-resistant prostate cancer [CRPC] eventually emerges. In recent years, several studies have demonstrated the importance of residual intratumoral androgens in maintaining androgen receptor (AR transcriptional activity in CRPC. The cytochrome P450 enzyme CYP17 is an obligatory step in androgen synthesis, and therefore a critical therapeutic target in CRPC. Abiraterone acetate is a selective, irreversible inhibitor of CYP17 and can suppress adrenal synthesis of androgen precursors, and possibly in situ steroidogenesis in the tumor microenvironment. In a phase III multicenter study, abiraterone in combination with prednisone improved median overall survival of men with docetaxel-refractory CRPC by 3.9 months compared to placebo plus prednisone, and also resulted in higher objective prostate-specific antigen and radiographic response rates. The study led to the FDA approval in April 2011 of abiraterone for treatment of chemotherapy-refractory CRPC patients, validating steroidogenesis and the AR axis in general as therapeutic targets in CRPC. The FDA indication for abiraterone was expanded to all CRPCs in December 2012, while evaluation in even earlier disease states is ongoing. We propose a comprehensive AR axis-targeting approach via simultaneous, frontline enzymatic blockade of several steroidogenic enzymes (eg, CYP17 and AKR1C3 in combination with gonadotropin-releasing hormone analogs and potent, second-generation AR antagonists (eg, enzalutamide in order to improve outcomes in patients with prostate cancer.Keywords: androgen synthesis, testosterone, dihydrotestosterone, CYP17, AKR1C3, MDV

  3. Immunotherapy and Immune Evasion in Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Thakur, Archana, E-mail: thakur@karmanos.org; Vaishampayan, Ulka [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Lum, Lawrence G., E-mail: thakur@karmanos.org [Department of Oncology, Wayne State University, Detroit, MI 48201 (United States); Department of Medicine, Wayne State University, Detroit, MI 48201 (United States); Department of Immunology and Microbiology, Wayne State University, Detroit, MI 48201 (United States)

    2013-05-24

    Metastatic prostate cancer remains to this day a terminal disease. Prostatectomy and radiotherapy are effective for organ-confined diseases, but treatment for locally advanced and metastatic cancer remains challenging. Although advanced prostate cancers treated with androgen deprivation therapy achieves debulking of disease, responses are transient with subsequent development of castration-resistant and metastatic disease. Since prostate cancer is typically a slowly progressing disease, use of immune-based therapies offers an advantage to target advanced tumors and to induce antitumor immunity. This review will discuss the clinical merits of various vaccines and immunotherapies in castrate resistant prostate cancer and challenges to this evolving field of immune-based therapies.

  4. Disseminated intravascular coagulation in a patient with metastatic prostate cancer: Fatal outcome following strontium-89 therapy

    Energy Technology Data Exchange (ETDEWEB)

    Leong, C.; McKenzie, R.; Coupland, D.B. [Univ. of British Columbia, (Canada)] [and others

    1994-10-01

    A patient with metastatic prostate cancer was found to have low-grade disseminated intravascular coagulation (DIC). He had significant bone pain despite external-beam radiotherapy and was given {sup 89}Sr with subsequent thrombocytopenia and epistaxis. The patient died from generalized hemorrhage 36 days postinjection. Although it is not possible to establish a causal relationship between {sup 89}Sr and DIC, practitioners should be alert to complications associated with the primary disorder which might occur at a time to raise concern about the intervention. 8 refs., 1 tab.

  5. Complete Response to Bicalutamide Withdrawal Prolonged for Almost 2 Years in Patients With Metastatic Prostate Cancer.

    Science.gov (United States)

    Hongo, Hiroshi; Kosaka, Takeo; Oya, Mototsugu

    2014-09-01

    This is the first case report describing a complete response to bicalutamide withdrawal that lasted for almost 2 years in a patient with metastatic prostate cancer. An 80-year-old man who had prostate-specific antigen (PSA) level elevation (168.1 ng/mL) visited our hospital in February 2010. Bone scintigraphy showed pelvic metastases. We started hormonal therapy with leuprorelin and bicalutamide. The PSA concentration decreased to <0.1 ng/mL but started increasing again and reached 1.64 ng/mL in October 2012, at which time bicalutamide administration was discontinued. The PSA concentration decreased again and has remained below the limit of sensitivity for almost 2 years.

  6. Enzalutamide Antitumour Activity Against Metastatic Castration-resistant Prostate Cancer Previously Treated with Docetaxel and Abiraterone

    DEFF Research Database (Denmark)

    Brasso, Klaus; Thomsen, Frederik B; Schrader, Andres J

    2015-01-01

    , AND PARTICIPANTS: Metastatic castration-resistant prostate cancer patients entering one of four European compassionate use programmes of enzalutamide. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was overall survival (OS). Secondary end points were association between OS and posttreatment...... prostate-specific antigen (PSA) kinetics, patient characteristics, and progression-free survival, respectively. Kaplan-Meier survival analysis and Cox proportional hazard analysis were performed. RESULTS AND LIMITATIONS: We identified 137 patients who prior to enzalutamide had progressed following a median....... Patients who had more than 30% or 50% falls in PSA had improved survival compared with patients who had no such PSA fall (11.4 mo vs 7.1 mo; p=0.001 and 12.6 vs 7.4 mo; p=0.007, respectively). Poor performance status and low haemoglobin was negatively associated with OS. CONCLUSIONS: Median OS...

  7. miR-129-3p controls centrosome number in metastatic prostate cancer cells by repressing CP110.

    Science.gov (United States)

    Bijnsdorp, Irene V; Hodzic, Jasmina; Lagerweij, Tonny; Westerman, Bart; Krijgsman, Oscar; Broeke, Jurjen; Verweij, Frederik; Nilsson, R Jonas A; Rozendaal, Lawrence; van Beusechem, Victor W; van Moorselaar, Jeroen A; Wurdinger, Thomas; Geldof, Albert A

    2016-03-29

    The centrosome plays a key role in cancer invasion and metastasis. However, it is unclear how abnormal centrosome numbers are regulated when prostate cancer (PCa) cells become metastatic. CP110 was previously described for its contribution of centrosome amplification (CA) and early development of aggressive cell behaviour. However its regulation in metastatic cells remains unclear. Here we identified miR-129-3p as a novel metastatic microRNA. CP110 was identified as its target protein. In PCa cells that have metastatic capacity, CP110 expression was repressed by miR-129-3p. High miR-129-3p expression levels increased cell invasion, while increasing CP110 levels decreased cell invasion. Overexpression of CP110 in metastatic PCa cells resulted in a decrease in the number of metastasis. In tissues of PCa patients, low CP110 and high miR-129-3p expression levels correlated with metastasis, but not with the expression of genes related to EMT. Furthermore, overexpression of CP110 in metastatic PCa cells resulted in excessive-CA (E-CA), and a change in F-actin distribution which is in agreement with their reduced metastatic capacity. Our data demonstrate that miR-129-3p functions as a CA gatekeeper in metastatic PCa cells by maintaining pro-metastatic centrosome amplification (CA) and preventing anti-metastatic E-CA.

  8. The Effect of Multiplicity of Metastatic Sites on Hormone Refractory Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Amal Halim

    2012-10-01

    Full Text Available Background: This study retrospectively evaluated the prognostic factors and treatment outcome of patients with hormone-refractory prostate cancer who received chemotherapy.Methods: We reviewed records of hormone-refractory prostate cancer patients who received chemotherapy between December 2004 and May 2011 at the Clinical Oncology and Nuclear Medicine Department, Mansoura University and the Oncology Outpatient Clinic of East Delta Insurance Institute, Egypt with regards to patient characteristics, response to chemotherapy, toxicity, survival and prognostic factors.Results: A total of 37 records were analyzed. Patients' median age was 66 years. The majority (70% had bone metastases. One patient received single agent prednisolone and 2 received single agent vinorelbine. There were 34 (92% who received a docetaxel based chemotherapy regimen for whom we determined the treatment outcome andprognostic factors. Patients underwent a median of six cycles of treatment (range: 4–11. Fourteen of 34 patients (%41 had ≥50% decrease in serum prostatic-surface antigen. Among 16 patients who had measurable disease at the baseline, 8 (50% achieved a partial response according to radiographic criteria. Of the 25 patients who experienced cancer pain before treatment initiation, 15 (60% reduced their analgesic drug intake. Grades 3-4 neutropenia occurred in 13 (38% patients. The median follow-up period was 13 months and the median event-free survival was 7 months (range: 4-31. The median overall survival period was 12 months (range: 4.5-37. According to multivariate regression analysis, multiplicity of metastatic sites was the only independent prognostic factor (P=0.005.Conclusions: Hormone-refractory prostate cancer is not considered totally resistant to chemotherapy. In this study, multiplicity of metastatic sites is the only independent prognostic factor. Survival figures are not satisfactory, therefore additional research is needed for achieving a better

  9. The CT flare response of metastatic bone disease in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Messiou, Christina; deSouza, Nandita M. (Cancer Research UK Clinical Magnetic Resonance Research Group, Inst. of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)), email: Christina.Messiou@icr.ac.uk; Cook, Gary (Dept. of Nuclear Medicine, Royal Marsden NHS Foundation Trust, Surrey (United Kingdom)); Reid, Alison H.M.; Attard, Gerhardt; Dearnaley, David; deBono, Johann S. (Inst. of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey (United Kingdom))

    2011-06-15

    Background New or worsening bone lesions in patients responding to treatment, known as the flare phenomenon is well described on 99mTc-MDP bone scintigraphy, but to our knowledge has not previously been described on CT. The appearance of new or worsening bone sclerosis on CT in patients with prostate cancer may therefore be erroneously classified as disease progression. Purpose To assess the incidence of osteoblastic healing flare response at 3-month CT assessment in patients with castrate-resistant prostate cancer and to identify associated features that enable differentiation from progressive metastatic bone disease at 3 months. Material and Methods CT scans of 67 patients with castrate-resistant prostate cancer undergoing treatment were reviewed by a radiologist blinded to clinical outcome. Changes in number, size, and density of metastatic bone lesions were documented and Response Evaluation Criteria in Solid Tumours (RECIST) in soft tissue lesions, alkaline phosphatase, prostate specific antigen, and 99mTc-MDP bone scans were used for correlation. Results Of the 39 patients who had 3- and 6-month follow-up, eight patients (21%) demonstrated an increase in number, size, or density of sclerotic lesions on the 3-month CT scan despite improvement in PSA and soft tissue lesions. Three out of eight patients (8%) maintained partial response/remained stable at follow-up and were defined as showing a flare response: in this group bone metastases evident on CT showed a qualitative and quantitative increase in density and no lesions faded at 3 months. In contrast, in all patients who progressed at 3 months by PSA/RECIST criteria (n = 8) bone lesions showed a mixed pattern with some lesions increasing and others decreasing in density. Conclusion The incidence of flare response of metastatic bone disease evident at 3-month post-treatment CT in patients with prostate cancer undergoing systemic treatment is 8%. In patients with falling PSA and stable/responding soft tissue

  10. Changes in extracellular matrix (ECM and ECM-associated proteins in the metastatic progression of prostate cancer

    Directory of Open Access Journals (Sweden)

    Sikes Robert A

    2004-01-01

    Full Text Available Abstract Prostate cancer (PCa is no exception to the multi-step process of metastasis. As PCa progresses, changes occur within the microenvironments of both the malignant cells and their targeted site of metastasis, enabling the necessary responses that result in successful translocation. The majority of patients with progressing prostate cancers develop skeletal metastases. Despite advancing efforts in early detection and management, there remains no effective, long-term cure for metastatic PCa. Therefore, the elucidation of the mechanism of PCa metastasis and preferential establishment of lesions in bone is an intensive area of investigation that promises to generate new targets for therapeutic intervention. This review will survey what is currently know concerning PCa interaction with the extracellular matrix (ECM and the roles of factors within the tumor and ECM microenvironments that contribute to metastasis. These will be discussed within the context of changes in expression and functional heterodimerization patterns of integrins, changes in ECM expression and reorganization by proteases facilitating invasion. In this context we also provide a brief summary of how growth factors (GFs, cytokines and regulatory signaling pathways favor PCa metastasis to bone.

  11. Targeted treatment of advanced and metastatic breast cancer with lapatinib

    Directory of Open Access Journals (Sweden)

    Brendan Corkery

    2008-09-01

    Full Text Available Brendan Corkery1,2, Norma O’Donovan2, John Crown1,21St. Vincent’s University Hospital, Dublin, Ireland; 2National Institute for Cellular Biotechnology, Dublin City University, Dublin, IrelandAbstract: Improved molecular understanding of breast cancer in recent years has led to the discovery of important drug targets such as HER-2 and EGFR. Lapatinib is a potent dual inhibitor of HER-2 and EGFR. Preclinical and phase I studies have shown activity with lapatinib in a number of cancers, including breast cancer, and the drug is well tolerated. The main known drug interactions are with paclitaxel and irinotecan. The most significant side-effects of lapatinib are diarrhea and adverse skin events. Rates of cardiotoxicity compare favorably with trastuzumab, a monoclonal antibody against HER-2. This paper focuses on lapatinib in advanced and metastatic breast cancer, which remains an important therapeutic challenge. Phase II and III studies show activity as monotherapy, and in combination with chemotherapy or hormonal agents. Results from these studies suggest that the main benefit from lapatinib is in the HER-2 positive breast cancer population. Combinations of lapatinib and trastuzumab are also being studied and show encouraging results, particularly in trastuzumab-refractory metastatic breast cancer. Lapatinib may have a specific role in treating HER-2 positive CNS metastases. The role of lapatinib as neoadjuvant therapy and in early breast cancer is also being evaluated.Keywords: HER-2, EGFR, erbB, lapatinib, Tykerb®, tyrosine kinase

  12. Treatment Outcomes in Non-Metastatic Prostate Cancer Patients With Ultra-High Prostate-Specific Antigen

    Energy Technology Data Exchange (ETDEWEB)

    Tai, Patricia, E-mail: ptai2@yahoo.com [Saskatchewan Cancer Agency, Regina, SK (Canada); Tonita, Jon; Woitas, Carla; Zhu Tong [Saskatchewan Cancer Agency, Regina, SK (Canada); Joseph, Kurian [Department of Oncology, Cross Cancer Institute, University of Alberta, Calgary, AB (Canada); Skarsgard, David [Department of Oncology, Tom Baker Cancer Center, University of Alberta, Calgary, AB (Canada)

    2012-07-15

    Purpose: It is commonly believed that prostate cancer patients with very high prostate-specific antigen (PSA) levels are unlikely to benefit from definitive local treatment, and patients with very high PSA are often underrepresented in, or excluded from, randomized clinical trials. Consequently, little is known about their optimal treatment or prognosis. We performed a registry-based analysis of management and outcome in this population of patients. Methods and Materials: Our provincial Cancer Registry was used to identify all men who were diagnosed with prostate cancer from 1990 to 2001. A retrospective chart review provided information on stage, Gleason score, PSA at diagnosis, and treatment. In this study, ultra-high PSA was defined as PSA of {>=}50 ng/ml. For a more complete perspective, treatment outcomes of patients with PSA of 20 to 49.9 ng/ml were also studied. Results: Of the 8378 men diagnosed with prostate cancer during this period, 6,449 had no known nodal or distant metastatic disease. The median follow-up of this group was 67.2 months (range, 0-192 months). A total of 1534 patients had PSA of {>=}20 ng/ml. Among the 995 patients with PSA 20 to 49.9 ng/ml, 85 had radical prostatectomy (RP), and their 5- and 10-year cause-specific survivals (CSS) were 95% and 84%, respectively. The 497 patients treated with radiotherapy (RT) had 5- and 10-year CSS of 92% and 71%. For the 332 patients with PSA 50-99.9 ng/ml, RT was associated with 5- and 10-year CSS of 81% and 55%. For the 207 patients with PSA of {>=}100 ng/ml, RT was associated with 5- and 10-year CSS of 80% and 54%. Conclusions: This is the largest series in the world on non metastatic cancer patients with ultra-high PSA at diagnosis. Even in the setting of a very high presenting PSA level, prostatectomy and radiotherapy are often associated with prolonged survival.

  13. Optimal Sequencing of New Drugs in Metastatic Castration-Resistant Prostate Cancer: Dream or Reality?

    Science.gov (United States)

    Caffo, Orazio; Lunardi, Andrea; Trentin, Chiara; Maines, Francesca; Veccia, Antonello; Galligioni, Enzo

    2016-01-01

    The availability of new drugs capable of improving the overall survival of patients with metastatic castration-resistant prostate cancer has led to the possibility of using them sequentially in the hope of obtaining a cumulative survival benefit. The new agents have already been administered as third-line treatments in patients who have previously received them as second line in everyday clinical practice, but the efficacy of this practice is not yet supported by clinical trial data, and evidence of possible cross-resistance has reinforced the debate concerning the best sequence to use in order to maximise the benefit. Furthermore, the situation is further complicated by the possibility of administering new hormonal agents to chemotherapy-naïve patients, and novel chemotherapeutic agents to hormone-sensitive patients. This article critically reviews the available data concerning the sequential use of new drugs, and discusses the real evidence concerning their optimal positioning in the therapeutic strategy of metastatic castration-resistant prostate cancer.

  14. Inverse Relationship Between Leydig Cell Density and Metastatic Potential of Prostatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    W. John Wang

    1999-01-01

    Full Text Available Purpose: Evaluate the relationship between metastatic potential of prostatic adenocarcinoma (PC and testicular Leydig cell density. Materials and methods: Tissue samples from 111 men, age 52–85, with PC and bilateral orchiectomy were evaluated for Leydig cell density. The patients were divided into two groups: Group A were patients with metastasis (n=36 and Group B were patients without metastasis (n=75. Leydig cell density was determined by direct manual microscopic cell count on the tissue sections. The means of cell counts by four pathologists, expressed as cell/0.78 mm2 were used for analysis. The normally distributed data were analyzed by two‐tail Student’s t‐test. Thirty‐eight age‐compatible autopsy cases who died of unrelated causes served as normal controls. Results: The mean of Leydig cell count in group A patients was 14.43 (14.43 ± 1.19 SE. Mean of Group B was 47.05 (47.05 ± 4.05 SE whereas normal controls displayed a mean of 48.66 (48.66 ± 2.94 SE. Group A was significantly different from control (p0.75. Conclusions: Patients with metastatic adenocarcinoma of prostate, as a group, have a significantly lower Leydig cell density than patients without metastasis or patients without PC in compatible age groups. The hormonal relationship between this observation is however unknown. One possible explanation is that PC subpopulation with metastatic potential may require different level of endogenous androgen or are androgen‐independent.

  15. Integrated Multimodal Imaging of Dynamic Bone-Tumor Alterations Associated with Metastatic Prostate Cancer

    NARCIS (Netherlands)

    Brisset, Jean-Christophe; Hoff, Benjamin A.; Chenevert, Thomas L.; Jacobson, Jon A.; Boes, Jennifer L.; Galban, Stefanie; Rehemtulla, Alnawaz; Johnson, Timothy D.; Pienta, Kenneth J.; Galban, Craig J.; Meyer, Charles R.; Schakel, Timothy; Nicolay, Klaas; Alva, Ajjai S.; Hussain, Maha; Ross, Brian D.; Schakel, Tim

    2015-01-01

    Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellul

  16. Improving radionuclide therapy in prostate cancer patients with metastatic bone pain

    NARCIS (Netherlands)

    Lam, M.G.E.H.

    2009-01-01

    Bone seeking radiopharmaceuticals are indicated in cancer patients with multiple painful skeletal metastases. The majority of these patients are hormone-refractory prostate cancer patients in an advanced stage of their disease. Bone seeking radiopharmaceuticals relieve pain and improve the patients

  17. Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells

    NARCIS (Netherlands)

    Chatterji, T.; Varkaris, A.S.; Parikh, N.U.; Song, J.H.; Cheng, C.J.; Schweppe, R.E.; Alexander, S.; Davis, J.W.; Troncoso, P.; Friedl, P.H.; Kuang, J.; Lin, S.H.; Gallick, G.E.

    2015-01-01

    To study the role of FAK signaling complexes in promoting metastatic properties of prostate cancer (PCa) cells, we selected stable, highly migratory variants, termed PC3 Mig-3 and DU145 Mig-3, from two well-characterized PCa cell lines, PC3 and DU145. These variants were not only increased migration

  18. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Robert B. Sims

    2011-01-01

    Full Text Available Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  19. Sipuleucel-T: autologous cellular immunotherapy for men with asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer.

    Science.gov (United States)

    Sims, Robert B

    2011-01-01

    Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  20. Sipuleucel-T: Autologous Cellular Immunotherapy for Men with Asymptomatic or Minimally Symptomatic Metastatic Castrate Resistant Prostate Cancer

    OpenAIRE

    Sims, Robert B.

    2011-01-01

    Sipuleucel T is an autologous cellular immunotherapy designed to stimulate an immune response in men diagnosed with asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer. Sipuleucel T improves overall survival and provides an additional treatment option for this patient population.

  1. Cabazitaxel in patients with metastatic castration-resistant prostate cancer: results of a compassionate use program in the Netherlands

    NARCIS (Netherlands)

    Wissing, M.D.; Oort, I.M. van; Gerritsen, W.R.; Eertwegh, A.J. van den; Coenen, J.L.; Bergman, A.M.; Gelderblom, H.

    2013-01-01

    BACKGROUND: Cabazitaxel has been reimbursed as a second-line therapy for patients with metastatic castrate-resistant prostate cancer (mCRPC) in the Netherlands since 2011. Before reimbursement was available, cabazitaxel was provided through a Compassionate Use Program (CUP). We report the results of

  2. Metastatic adenocarcinoma of prostate in a 28-year-old male: The outcome is poor in young patients?

    Directory of Open Access Journals (Sweden)

    Renu Madan

    2015-01-01

    Full Text Available Prostate cancer is common in older patients. Rarity in younger population limits the study of natural history and prognosis in this population. Most of the published data has reported poor outcome in younger patients with metastatic prostate cancer. Here, we report a case of prostate cancer in 28-year-old male who presented with bone metastasis. After bilateral inguinal orchidectomy, he was started on anti-androgen therapy and received palliative radiotherapy for bone metastasis. There was only a slight decrease in prostate-specific antigen (PSA level and pelvic disease post treatment. Subsequently, he was started on opioid analgesics (by World Health Organization, WHO, step ladder in view of persistent pain. The index case is being presented for its rarity and probable poor outcome in young patients and to stress on the fact that the possibility of primary prostatic adenocarcinoma should be investigated in a male presenting with bone metastasis irrespective of the age.

  3. Contemporary agents in the management of metastatic castration-resistant prostate cancer

    Science.gov (United States)

    Kapoor, Anil; Wu, Christopher; Shayegan, Bobby; Rybak, Adrian P.

    2016-01-01

    Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC. Cabazitaxel, abiraterone acetate, and enzalutamide are three agents recently approved for the treatment of mCRPC, having shown overall survival benefit in patients previously treated with docetaxel, while both abiraterone acetate and enzalutamide have also shown promise in the pre-docetaxel setting. Sipuleucel-T has shown overall survival benefit in asymptomatic mCRPC, while radium-223 provides survival benefit to patients with mCRPC who are symptomatic from their skeletal metastases in both docetaxel-naïve patients and post-docetaxel patients. Denosumab, an anti-RANKL antibody, has been approved for the prevention of skeletal-related events in patients with prostate cancer bone metastases. This review examines the phase 3 trials supporting the use of theses novel agents in the treatment of mCRPC. While these agents provide incremental increases in patient survival, further study to determine the best choice, combination, and/or sequencing of administration is still necessary. PMID:28096932

  4. Combined effects of terazosin and genistein on a metastatic, hormone-independent human prostate cancer cell line.

    Science.gov (United States)

    Chang, Kee-Lung; Cheng, Hsiao-Ling; Huang, Li-Wen; Hsieh, Bau-Shan; Hu, Yu-Chen; Chih, Tsai-Tung; Shyu, Huey-Wen; Su, Shu-Jem

    2009-04-08

    Metastatic prostate cancer progresses from androgen-dependent to androgen-independent. Terazosin, a long-acting selective alpha1-adrenoreceptor antagonist, induces apoptosis of prostate cancer cells in an alpha1-adrenoreceptor-independent manner, while genistein, a major soy isoflavone, inhibits the growth of several types of cancer cells. The present study was designed to test the therapeutic potential of a combination of terazosin and genistein using a metastatic, hormone-independent prostatic cancer cell line, DU-145. Terazosin or genistein treatment inhibited the growth of DU-145 cells in a dose-dependent manner, whereas had no effect on normal prostate epithelial cells. Addition of 1 microg/ml of terazosin, which was inactive alone, augmented the growth inhibitory effect of 5 microg/ml of genistein. Co-treatment with terazosin resulted in the genistein-induced arrest of DU-145 cells in G2/M phase being overridden and an increase in apoptotic cells, as evidenced by procaspase-3 activation and PARP cleavage. The combination also caused a greater decrease in the levels of the apoptosis-regulating protein, Bcl-XL, and of VEGF165 and VEGF121 than genistein alone. In conclusion, the terazosin/genistein combination was more effective in inhibiting cell growth and VEGF expression as well as inducing apoptosis of the metastatic, androgen-independent prostate cancer cell line, DU-145, than either alone. The doses used in this study are in lower and nontoxic anticancer dosage range, suggesting this combination has potential for therapeutic use.

  5. COX2 genetic variation, NSAIDs, and advanced prostate cancer risk

    OpenAIRE

    Cheng, I.; Liu, X.; Plummer, S J; Krumroy, L M; Casey, G; Witte, J S

    2007-01-01

    Collective evidence suggests that cyclooxygenase 2 (COX2) plays a role in prostate cancer risk. Cyclooxygenase 2 is the major enzyme that converts arachidonic acid to prostaglandins, which are potent mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzymatic activity of COX2 and long-term use of NSAIDs appears to modestly lower the risk of prostate cancer. We investigated whether common genetic variation in COX2 influences the risk of advanced prostate canc...

  6. Efficacy of c-Met inhibitor for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Christensen James G

    2010-10-01

    Full Text Available Abstract Background Aberrant expression of HGF/SF and its receptor, c-Met, often correlates with advanced prostate cancer. Our previous study showed that expression of c-Met in prostate cancer cells was increased after attenuation of androgen receptor (AR signalling. This suggested that current androgen ablation therapy for prostate cancer activates c-Met expression and may contribute to development of more aggressive, castration resistant prostate cancer (CRPC. Therefore, we directly assessed the efficacy of c-Met inhibition during androgen ablation on the growth and progression of prostate cancer. Methods We tested two c-Met small molecule inhibitors, PHA-665752 and PF-2341066, for anti-proliferative activity by MTS assay and cell proliferation assay on human prostate cancer cell lines with different levels of androgen sensitivity. We also used renal subcapsular and castrated orthotopic xenograft mouse models to assess the effect of the inhibitors on prostate tumor formation and progression. Results We demonstrated a dose-dependent inhibitory effect of PHA-665752 and PF-2341066 on the proliferation of human prostate cancer cells and the phosphorylation of c-Met. The effect on cell proliferation was stronger in androgen insensitive cells. The c-Met inhibitor, PF-2341066, significantly reduced growth of prostate tumor cells in the renal subcapsular mouse model and the castrated orthotopic mouse model. The effect on cell proliferation was greater following castration. Conclusions The c-Met inhibitors demonstrated anti-proliferative efficacy when combined with androgen ablation therapy for advanced prostate cancer.

  7. Neuroendocrine differentiation in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Jiaoti Huang

    2008-01-01

    @@ The treatment of choice for advanced/metastatic prostate cancer(PC) is hormonal therapy. Although patients respond initially to this therapy, the tumor will recur and enter the androgen-independent state, which is the major obstacle in therapy.

  8. uPAR Targeted Radionuclide Therapy with 177Lu-DOTA-AE105 Inhibits Dissemination of Metastatic Prostate Cancer

    DEFF Research Database (Denmark)

    Persson, Morten; Juhl, Karina; Rasmussen, Palle

    2014-01-01

    value of 100 nM in a competitive binding experiment. In vivo, uPAR targeted radionuclide therapy significantly reduced the number of metastatic lesions in the disseminated metastatic prostate cancer model, when compared to vehicle and nontargeted 177Lu groups (p bioluminescence imaging...... with bioluminescence imaging in a cohort of animals during the treatment study. In conclusion, uPAR targeted radiotherapy resulted in a significant reduction in the number of metastatic lesions in a human metastatic prostate cancer model. Furthermore, we have provided the first evidence of the potential...

  9. Serum methionine metabolites are risk factors for metastatic prostate cancer progression.

    Directory of Open Access Journals (Sweden)

    Sally Stabler

    Full Text Available BACKGROUND: Clinical decision for primary treatment for prostate cancer is dictated by variables with insufficient specificity. Early detection of prostate cancer likely to develop rapid recurrence could support neo-adjuvant therapeutics and adjuvant options prior to frank biochemical recurrence. This study compared markers in serum and urine of patients with rapidly recurrent prostate cancer to recurrence-free patients after radical prostatectomy. Based on previous identification of urinary sarcosine as a metastatic marker, we tested whether methionine metabolites in urine and serum could serve as pre-surgical markers for aggressive disease. METHODOLOGY/PRINCIPAL FINDINGS: Urine and serum samples (n = 54 and 58, respectively, collected at the time of prostatectomy were divided into subjects who developed biochemical recurrence within 2 years and those who remained recurrence-free after 5 years. Multiple methionine metabolites were measured in urine and serum by GC-MS. The role of serum metabolites and clinical variables (biopsy Gleason grade, clinical stage, serum prostate specific antigen [PSA] on biochemical recurrence prediction were evaluated. Urinary sarcosine and cysteine levels were significantly higher (p = 0.03 and p = 0.007 respectively in the recurrent group. However, in serum, concentrations of homocysteine (p = 0.003, cystathionine (p = 0.007 and cysteine (p<0.001 were more abundant in the recurrent population. The inclusion of serum cysteine to a model with PSA and biopsy Gleason grade improved prediction over the clinical variables alone (p<0.001. CONCLUSIONS: Higher serum homocysteine, cystathionine, and cysteine concentrations independently predicted risk of early biochemical recurrence and aggressiveness of disease in a nested case control study. The methionine metabolites further supplemented known clinical variables to provide superior sensitivity and specificity in multivariable prediction models for

  10. Can we improve the definition of high-risk, hormone naïve, non-metastatic prostate cancer?

    Science.gov (United States)

    Tombal, Bertrand; Alcaraz, Antonio; James, Nicholas; Valdagni, Riccardo; Irani, Jacques

    2014-02-01

    To identify criteria beyond Tumour-Node-Metastasis (TMN)-, prostate-specific antigen (PSA)- and Gleason score-based standard classifications to enhance the stratification of non-metastatic high-risk prostate cancer. A detailed search of the literature was performed using PubMed. The authors reviewed the literature and used a modified Delphi approach to identify relevant approaches to enhance standard classifications. Specific criteria for high-risk prostate cancer vary across guidelines and clinical trials, reflecting the differing perspectives concerning the definition of 'risk' between different specialities within the urology/radiation oncology community. In addition to the present classifications, evidence exists that the measure of cancer volume can provide additional prognostic value. More accurate imaging, especially multiparametric magnetic resonance imaging can also provide information concerning staging and cancer volume, and thus may assist in the identification of patients with high-risk prostate cancer. A refined definition of non-metastatic high-risk prostate cancer is proposed. Within this high-risk cohort, patients with multiple high-risk criteria are especially at risk of prostate cancer-specific mortality.

  11. Maximal androgen blockade versus castration alone in patients with metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Abeer A.Mahmoud; Eman A.El-Sharawy; Mohamed M.El-Bassiouny; Ramy R.Ghali

    2014-01-01

    Objective: Maximum androgen blockade (MAB), consisting of an antiandrogen plus either a luteinizing hormone-releasing hormone agonist (LHRHA) or orchiectomy, is a standard care for patients with prostate cancer. Although, clinical trial results have been equivocal, none has shown a significant advantage in favor of MAB over castration alone in metastatic prostate cancer and MAB has been the subject of considerable controversy. The aim of this study was to compare MAB (orchiectomy or LHRHA “Goserelin”) and anti-androgen “Bicalutamide” with castration alone (orchiectomy or LHRHA) in previ-ously untreated metastatic prostate cancer patients.Methods: Hundred eligible patients with adequate performance status and adequate hematologic, hepatic and renal functions were included. MAB arm, fifty patients underwent castration either surgicaly by orchiectomy or medicaly by receiving Goserelin (3.6 mg) depot, which was injected subcutaneously every 28 days plus bicalutamide 50 mg once daily. Castration alone arm, fifty patients underwent castration alone either surgicaly by orchiectomy or medicaly by receiving Goserelin (3.6 mg) depot.Results: During the period from January 2011 to January 2013, with a median folow up of 18 months (range 6 to 24 months), there were eight deaths (16%), in MAB arm and ten deaths (20%) in castration alone arm. At three months, there were 35 patients (70%) with prostate specific antigen (PSA) normalization (≤ 4 mg/dL) in MAB arm versus 17 patients (34%) with PSA normalization in castration alone arm (P = 0.001). The median progression free survival (PFS) times were 22.18 months (95% CI, 19.7 to 24.2 months) for MAB arm versus 22 months in castration alone arm (95% CI, 18 to 25.9 months;P = 0.045). The survival rates for MAB arm were 82% at 18 months and 70.6% at 24 months versus 78.7% at 18 months and 75.1% at 24 months in castration alone arm (P > 0.05). The median overal survival (OS) was not reached in either arm. Both hematological

  12. Robotic Image-Guided Stereotactic Radiotherapy, for Isolated Recurrent Primary, Lymph Node or Metastatic Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jereczek-Fossa, Barbara Alicja, E-mail: barbara.jereczek@ieo.it [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); University of Milan, Milan (Italy); Beltramo, Giancarlo [CyberKnife Center CDI, Milan (Italy); Fariselli, Laura [Radiotherapy Unit, Carlo Besta Neurological Institute Foundation, Milan (Italy); Fodor, Cristiana [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); Santoro, Luigi [Department of Epidemiology and Statistics, European Institute of Oncology, Milan (Italy); Vavassori, Andrea; Zerini, Dario [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); Gherardi, Federica [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); University of Milan, Milan (Italy); Ascione, Carmen [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); Seconda Universita degli Studi di Napoli, Naples (Italy); Bossi-Zanetti, Isa; Mauro, Roberta [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); University of Milan, Milan (Italy); Bregantin, Achille; Bianchi, Livia Corinna [CyberKnife Center CDI, Milan (Italy); De Cobelli, Ottavio [Department of Urology, European Institute of Oncology, Milan (Italy); Orecchia, Roberto [Department of Radiotherapy, European Institute of Oncology, Milan (Italy); University of Milan, Milan (Italy)

    2012-02-01

    Purpose: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. Methods and Materials: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [{sup 11}C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). Results: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. Conclusions: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor

  13. Health Economics and Radium-223 (Xofigo®) in the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC): A Case History and a Systematic Review of the Literature

    OpenAIRE

    Norum, Jan; Traasdahl, Erik R.; Totth, Arpad; Nieder, Carsten; Olsen, Jan Abel

    2015-01-01

    DOI: 10.5539/gjhs.v8n4p1 Creative Commons Attribution License 3.0 OBJECTIVES: Prostate cancer (PC) is the most common cancer in Western countries. Recent advances in the treatment of metastatic castration resistant prostate cancer (mCRPC) have caused significant pressure on health care budgets. We aimed to exemplify this dilemma presenting an example, radium-223 (Xofigo®), and review the literature. METHODS: A 74-year-old man diagnosed with mCRPC was referred to our department in O...

  14. Toward Maximizing Immunotherapy in Metastatic Castration Resistant Prostate Cancer – Rationale for Combinatorial Approaches Using Chemotherapy

    Directory of Open Access Journals (Sweden)

    Susan F Slovin

    2012-05-01

    Full Text Available Prostate cancer is particularly suited for active immunotherapy because of the expression of a distinctive number of antigens which are overexpressed on prostate cancer cells and cell lines. There is evidence in this disease that tumors promote immune tolerance starting early in the disease course. As such, chemotherapy, by suppressing tumors and activating immune system homeostatic mechanisms, may help overcome this tumor-induced immune tolerance. Sipuleucel-T which has recently been approved in the US, is an autologous cellule product immunotherapy that induces immune activity likely through activation of dendritic cells. This was associated with a survival benefit in the absence of significant toxicity. However, a post hoc analysis of phase III trial participants found a substantial survival benefit to receiving docetaxel some months after sipuleucel-T. However, another phase III immunotherapy trial combining a prostate cancer therapeutic vaccine G-VAX plus docetaxel versus standard docetaxel therapy in advanced prostate cancer, observed a lower overall survival with the vaccine regimen. These trials highlight major unresolved questions concerning the optimum choice, dosing, and timing of chemotherapy relative to active immunotherapy and the overall merits of considering this approach. The ideal treatment approach remains unclear; advances in biomarker validation and trial design may likely improve our ability to assess biologic benefit irrespective of the development of true anti-tumor immunity.

  15. A single-center experience with abiraterone as treatment for metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Thortzen, Anita; Thim, Stine; Røder, Martin Andreas;

    2016-01-01

    BACKGROUND: Continuous stimulation of the androgen receptor (AR) axis is a prerequisite for growth in castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) is a potent inhibitor of extracellular and intracellular androgen synthesis by inhibition of the CYP-17 enzyme system, which...... has been shown to be up-regulated in CRPC. AA was recently introduced in the management of patients with metastatic CRPC (mCRPC) both before and after taxane-based chemotherapy. The purpose of this study is to report the initial clinical experience obtained from mCRPC patients managed on AA......% of the patients. Time to biochemical and radiological progression was 3.5 and 4.9 months, respectively. Overall survival was 13.2 months (95% CI: 9.0-17.4). CONCLUSION: Our initial experience with AA in the routine management of patients with mCRPC demonstrates an efficacy-effectiveness gap compared with clinical...

  16. Challenges to improved therapeutics for metastatic castrate resistant prostate cancer: from recent successes and failures

    Directory of Open Access Journals (Sweden)

    Huang Xuan

    2012-07-01

    Full Text Available Abstract Men with metastatic castration-resistant prostate cancer (mCRPC carry poor prognosis despite the use of docetaxel-based regimens which has modest survival benefit shown by randomized clinical trials. Significant progress in the discovery of novel therapeutic agents has been made in the past few years. While sipuleucel-T, cabazitaxel, and abiraterone gained regulatory approval in 2010 and 2011, several highly promising candidates/regimens have failed in large scale clinical trials. Challenges remain to optimize the design and interpretation of clinical trial results and develop more effective strategies for mCRPC. In this review, we examined the positive and negative clinical trials in mCRPC in the past and discussed the various aspects of clinical trial design including selection of targets and appropriate outcome measures, biomarker development and implementation, and strategies for combination therapy.

  17. Challenges in the sequencing of therapies for the management of metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Parente, Phillip; Parnis, Francis; Gurney, Howard

    2014-09-01

    Prior to 2010, docetaxel was the standard option for chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC). Today, the picture is vastly different: several additional therapies have each demonstrated a survival benefit such that we now have chemotherapy (cabazitaxel), androgen suppressive agents (abiraterone acetate and enzalutamide), a cellular vaccine (sipuleucel-T) and radium-233 (for symptomatic bone metastases). With several other agents in the pipeline for late-stage disease, the future looks promising for mCRPC. As the available data are not able to inform as to the optimum sequencing of therapy, this remains a challenge. This paper draws on insights from published and ongoing clinical studies to provide a practical patient-focused approach to maximize the benefits of the current therapeutic armamentarium. Preliminary sequencing suggestions are made based on clinical trial criteria. But until more data become available, clinical gestalt, experience, cost and individual patient preferences will continue to drive choices.

  18. Advantages and Disadvantages of Bone Protective Agents in Metastatic Prostate Cancer: Lessons Learned

    Directory of Open Access Journals (Sweden)

    Christian Thomas

    2016-08-01

    Full Text Available Nine out of ten metastatic prostate cancer (PCa patients will develop osseous metastases. Of these, every second will suffer from skeletal-related events (SRE. SRE are associated with an increased risk for death, which is markedly increased in the presence of pathological fracture. Moreover, health insurance costs nearly double in the presence of SRE. Zoledronic acid and denosumab are both approved drugs for the prevention or delay of SRE in castration-resistant prostate cancer (CRPC patients with osseous metastases. However, long-term treatment with one of these two drugs is associated with the development of medication-related osteonecrosis of the jaw (MRONJ. Routine inspections of the oral cavity before and during treatment are mandatory in these patients. Regarding imaging techniques, bone scintigraphy seems to be a promising tool to detect early stage MRONJ. Zoledronic acid does not reduce the incidence of SRE in hormone-sensitive PCa. First data shows 3-monthly application of zoledronic acid to be equi-effective to monthly application.

  19. Dose escalation study of rhenium-186 hydroxyethylidene diphosphonate in patients with metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Klerk, J.M.H. de (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands)); Zonnenberg, B.A. (Oncology Section, Dept. of Internal Medicine, Univ. Hospital, Utrecht (Netherlands)); Schip, A.D. van het (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands)); Dijk, A. van (Center for Hospital Pharmacy, Univ. Hospital, Utrecht (Netherlands)); Han, S.H. (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands)); Quirijnen, J.M.S.P. (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands)); Blijham, G.H. (Oncology Section, Dept. of Internal Medicine, Univ. Hospital, Utrecht (Netherlands)); Rijk, P.P. van (Dept. of Nuclear Medicine, Univ. Hospital, Utrecht (Netherlands))

    1994-10-01

    Rhenium-186 hydroxyethylidene diphosphonate ([sup 186]Re-HEDP) has been used for the palliative treatment of metastatic bone pain. A phase 1 dose escalation study was performed using [sup 186]Re-HEDP. Twenty-four patients with hormone-resistant prostate cancer entered the study. Each patient had at least four bone metastases and adequate haematological function. Groups of at least three consecutive patients were treated with doses starting at 1295 MBq and increasing to 3515 MBq (escalated in increments of 555 MBq). Thrombocytopenia proved to be the dose-limiting toxicity, while leucopenia played a minor role. Early death occurred in one patient (10 days after administration) without clear relationship to the [sup 186]Re-HEDP therapy. Transient neurological dysfunction was seen in two cases. Two patients who received 3515 MBq [sup 186]Re-HEDP showed grade 3 toxicity (thrombocytes 25-50 x 10[sup 9]/l), defined as unacceptable toxicity. After treatment alkaline phosphatase levels showed a transient decrease in all patients (mean: 26% [+-] 10% IU/l; range: 11%-44%). Prostate-specific antigen values showed a decline in eight patients, preceded by a temporary increase in three patients. From this study we conclude that the maximally tolerated dose of [sup 186]Re-HEDP is 2960 MBq. A placebo-controlled comparative study on the efficacy of [sup 186]Re-HEDP has been initiated. (orig.)

  20. Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

    Directory of Open Access Journals (Sweden)

    Vanita Noronha

    2016-08-01

    Full Text Available Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC patients from the named patient programme (NPP at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27 under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80 and progression-free survival was 2.67 months (1.07–20.27. QOL was stable for most patients. Common adverse events (grade ≥3 were neutropenia (n = 8, anaemia (n = 4, and leucopenia (n = 4. Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

  1. Sipuleucel-T for the Treatment of Patients With Metastatic Castrate-resistant Prostate Cancer: Considerations for Clinical Practice.

    Science.gov (United States)

    Pieczonka, Christopher M; Telonis, Dimitrios; Mouraviev, Vladimir; Albala, David

    2015-01-01

    Sipuleucel-T treatment is associated with a significant and consistent survival benefit in patients with metastatic castrate-resistant prostate cancer. Most adverse events are infusion related, manageable, and of short duration. Early screening and diagnosis of metastatic disease is important, as the greatest survival benefit may occur in patients with a lower disease burden. The short duration of sipuleucel-T treatment facilitates the use of subsequent therapies. Sipuleucel-T is now being used in the clinic for patients with a lower disease burden. We present our own experience with the use of sipuleucel-T in the setting of a large urology practice.

  2. Identification of Bone-Derived Factors Conferring De Novo Therapeutic Resistance in Metastatic Prostate Cancer.

    Science.gov (United States)

    Lee, Yu-Chen; Lin, Song-Chang; Yu, Guoyu; Cheng, Chien-Jui; Liu, Bin; Liu, Hsuan-Chen; Hawke, David H; Parikh, Nila U; Varkaris, Andreas; Corn, Paul; Logothetis, Christopher; Satcher, Robert L; Yu-Lee, Li-Yuan; Gallick, Gary E; Lin, Sue-Hwa

    2015-11-15

    Resistance to currently available targeted therapies significantly hampers the survival of patients with prostate cancer with bone metastasis. Here we demonstrate an important resistance mechanism initiated from tumor-induced bone. Studies using an osteogenic patient-derived xenograft, MDA-PCa-118b, revealed that tumor cells resistant to cabozantinib, a Met and VEGFR-2 inhibitor, reside in a "resistance niche" adjacent to prostate cancer-induced bone. We performed secretome analysis of the conditioned medium from tumor-induced bone to identify proteins (termed "osteocrines") found within this resistance niche. In accordance with previous reports demonstrating that activation of integrin signaling pathways confers therapeutic resistance, 27 of the 90 osteocrines identified were integrin ligands. We found that following cabozantinib treatment, only tumor cells positioned adjacent to the newly formed woven bone remained viable and expressed high levels of pFAK-Y397 and pTalin-S425, mediators of integrin signaling. Accordingly, treatment of C4-2B4 cells with integrin ligands resulted in increased pFAK-Y397 expression and cell survival, whereas targeting integrins with FAK inhibitors PF-562271 or defactinib inhibited FAK phosphorylation and reduced the survival of PC3-mm2 cells. Moreover, treatment of MDA-PCa-118b tumors with PF-562271 led to decreased tumor growth, irrespective of initial tumor size. Finally, we show that upon treatment cessation, the combination of PF-562271 and cabozantinib delayed tumor recurrence in contrast to cabozantinib treatment alone. Our studies suggest that identifying paracrine de novo resistance mechanisms may significantly contribute to the generation of a broader set of potent therapeutic tools that act combinatorially to inhibit metastatic prostate cancer.

  3. Enzalutamide: targeting the androgen signalling pathway in metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Schalken, Jack; Fitzpatrick, John M

    2016-02-01

    Significant progress has been made in the understanding of the underlying cancer biology of castration-resistant prostate cancer (CRPC) with the androgen receptor (AR) signalling pathway remaining implicated throughout the prostate cancer disease continuum. Reactivation of the AR signalling pathway is considered to be a key driver of CRPC progression and, as such, the AR is a logical target for therapy in CRPC. The objective of this review was to understand the importance of AR signalling in the treatment of patients with metastatic CRPC (mCRPC) and to discuss the clinical benefits associated with inhibition of the AR signalling pathway. A search was conducted to identify articles relating to the role of AR signalling in CRPC and therapies that inhibit the AR signalling pathway. Current understanding of prostate cancer has identified the AR signalling pathway as a logical target for the treatment of CRPC. Available therapies that inhibit the AR signalling pathway include AR blockers, androgen biosynthesis inhibitors, and AR signalling inhibitors. Enzalutamide, the first approved AR signalling inhibitor, has a novel mode of action targeting AR signalling at three key stages. The direct mode of action of enzalutamide has been shown to translate into clinical responses in patients with mCRPC. In conclusion, the targeting of the AR signalling pathway in patients with mCRPC results in numerous clinical benefits. As the number of treatment options increase, more trials evaluating the sequencing and combination of treatments are required. This review highlights the continued importance of targeting a key driver in the progression of CRPC, AR signalling, and the clinical benefits associated with inhibition of the AR signalling pathway in the treatment of patients with CRPC.

  4. Zoladex plus flutamide vs. orchidectomy for advanced prostatic cancer. Danish Prostatic Cancer Group (DAPROCA)

    DEFF Research Database (Denmark)

    Iversen, P

    1990-01-01

    The study comprised 262 patients with previously untreated advanced carcinoma of the prostate. Patients were randomized either to undergo orchidectomy or to receive combined treatment with Zoladex, 3.6 mg every 4 weeks, plus flutamide, 250 mg t.i.d. At present the median follow-up is 39 months......' with Zoladex plus flutamide was not clinically superior to orchidectomy in the treatment of patients with advanced prostatic cancer....

  5. Treatment of Hormone Resistance with Docetaxel in Metastatic Prostate Cancer Patients: Results of a Clinical Experience at Omid Hospital, Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Mina Tajvidi

    2017-01-01

    Full Text Available Background: Metastatic prostate cancer is one of the most important cancers among men worldwide. Androgen ablation therapy can be used in treatment of these patients; however, most will progress to metastatic hormone-refractory prostate cancer. In this regard, docetaxel has been approved to treat metastatic hormone-refractory prostate cancer in the United States. In this study, we aimed to investigate the results of this treatment modality in metastatic prostate cancer patients from Iran. Methods:We evaluated PSA response and bone pain relief in 18 metastatic prostate cancer patients who underwent treatment with docetaxel at a dose of 75 mg/m2 intravenously on the first day of treatment. The treatment was repeated every three weeks (6 cycles along with 10 mg of prednisolone. Results: Of 18 patients, 39% had >50% decline in PSA levels.There were 16% of the patients with a PSA decline of approximately 30% to 50% of the pre-treatment levels. In addition, 29% of the patients had progressive PSA levels during chemotherapy. Among them, 55% had significant pain relief. Conclusion: This research showed the effectiveness of docetaxel to decrease PSA levels in metastatic hormone-refractory prostate cancer patients from Iran. Docetaxel was also valuable in alleviation of pain in these patients. However, prospective studies should validate this approach.

  6. Vismodegib: a guide to its use in locally advanced or metastatic basal cell carcinoma.

    Science.gov (United States)

    Lyseng-Williamson, Katherine A; Keating, Gillian M

    2013-02-01

    Vismodegib is the first Hedgehog pathway inhibitor to be approved in the USA, where it is indicated for the treatment of adults with metastatic basal cell carcinoma (BCC), or with locally advanced BCC that has recurred following surgery or who are not candidates for surgery, and who are not candidates for radiation. In an ongoing, noncomparative, phase II trial, oral vismodegib was effective in and had an acceptable tolerability profile in the treatment of patients with locally advanced or metastatic BCC.

  7. Low-dose prednisolone in first-line docetaxel for patients with metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge Marie; Lindberg, Henriette;

    2015-01-01

    BACKGROUND: Randomized studies have shown improved survival with the combination of docetaxel (D) and prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC). We retrospectively investigated whether coadministration of low-dose glucocorticoids has clinical benefits.......001). P did not influence progression-free survival (P = 0.692, log-rank test) or overall survival when adjusting for baseline levels of hemoglobin, alkaline phosphatase, lactate dehydrogenase, prostate-specific antigen, and Eastern Cooperative Oncology Group performance status (hazard ratioP = 0.98, 95...

  8. Piecing the Puzzle Together: Docetaxel Cycles and Current Considerations in the Treatment of Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Feinman, Hannah E; Price, Douglas K; Figg, William D

    2017-02-25

    Docetaxel is the current first line therapy for metastatic castration-resistant prostate cancer (mCRPC), but there is no standard number of docetaxel cycles given to patients. In their post hoc analysis of the Mainsail study, de Morrée et al. show that the number of docetaxel cycles administered to a patient is a significant factor contributing to overall survival. These findings warrant further investigation into the standardization of the number of docetaxel cycles administered.

  9. Combined androgen blockade in the treatment of advanced prostate cancer--an overview. The Scandinavian Prostatic Cancer Group

    DEFF Research Database (Denmark)

    Iversen, P

    1997-01-01

    The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed.......The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed....

  10. Denosumab Reduces Risk of Bone Side Effects in Advanced Prostate Cancer

    Science.gov (United States)

    The biological agent denosumab (Xgeva) is more effective than zoledronic acid at decreasing the risk of bone fractures and other skeletal-related events (SRE) in men with castration-resistant metastatic prostate cancer, according to results from a randomi

  11. Successful sperm extraction and live birth after radiation, androgen deprivation and surgical castration for treatment of metastatic prostate cancer.

    Science.gov (United States)

    Wood, G J A; Hayden, R P; Tanrikut, C

    2017-02-01

    Fertility preservation has become an important aspect of cancer treatment given the gonadotoxic effects of oncologic therapies. It is now considered standard of care to offer sperm banking to men undergoing treatment for primaries that affect young individuals. Less is known regarding fertility preservation of patients afflicted with prostate cancer. This cohort has progressively expanded and grown younger in the post-PSA era. Prostatectomy, radiation, chemotherapy and androgen blockade all pose unique challenges to the infertility specialist. Optimum management becomes even more uncertain for those men with metastatic prostate cancer. Most of these individuals will have received multiple forms of therapy, each carrying a distinct insult to the patient's reproductive potential. We describe a case of successful ex vivo sperm extraction and live birth in a patient previously treated with radiation and chronic androgen deprivation for metastatic prostate cancer. The presented case demonstrates that conception after radiation therapy and chronic androgen deprivation is feasible. We propose that fertility counselling and sperm cryopreservation should be considered for all prostate cancer patients. Additionally, for those individuals undergoing external beam radiotherapy, testicular shielding should be routinely offered in the event further family building is desired.

  12. Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, R.G.; Blake, G.M.; Preston, D.F.; McEwan, A.J.; Spicer, J.A.; Martin, N.L.; Wegst, A.V.; Ackery, D.M.

    1989-03-01

    Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

  13. Strontium-89: treatment results and kinetics in patients with painful metastatic prostate and breast cancer in bone.

    Science.gov (United States)

    Robinson, R G; Blake, G M; Preston, D F; McEwan, A J; Spicer, J A; Martin, N L; Wegst, A V; Ackery, D M

    1989-03-01

    Two hundred and two patients with bone pain from metastatic cancer were treated with 40 microCi/kg of Sr-89. Patients were followed with pain diaries, records of medication taken, sleep patterns, serial bone scans and a Karnofsky Index. One hundred and thirty-seven patients with adequate followup survived at least 3 months, including 100 with prostate and 28 with breast carcinoma. Eighty of the 100 patients with prostate cancer responded, and 25 of the 28 breast cancer patients improved. Ten patients with prostate cancer and five with breast cancer became pain free. Little hematologic depression was noted. Sr-89 kinetic studies showed that strontium taken up in osteoblastic areas remained for 100 days. The tumor-to-marrow absorbed dose ratio was 10:1.

  14. Advanced prostate cancer risk in relation to toenail selenium levels

    NARCIS (Netherlands)

    Geybels, M.S.; Verhage, B.A.J.; Schooten, F.J. van; Goldbohm, A.; Brandt, P.A. van den

    2013-01-01

    BACKGROUND: Selenium may prevent advanced prostate cancer (PCa), but most studies on this topic were conducted in populations with moderate to high selenium status. We investigated the association of toenail selenium, reflecting long-term selenium exposure, and advanced PCa risk in a population from

  15. Pharmacodynamic study of Disulfiram in Men with Non-metastatic Recurrent Prostate Cancer

    Science.gov (United States)

    Schweizer, Michael T.; Lin, Jianqing; Blackford, Amanda; Bardia, Aditya; King, Serina; Armstrong, Andrew J.; Rudek, Michelle A.; Yegnasubramanian, Srinivasan; Carducci, Michael A.

    2013-01-01

    Background Preclinical drug screens identified disulfiram as a potent in vitro inhibitor of prostate cancer cell growth. Although many mechanisms for its anticancer activity have been proposed, tumor suppressor gene re-expression through promoter demethylation emerged as one of the more plausible. Methods We conducted an open-label, dose escalation trial of disulfiram in men with non-metastatic recurrent prostate cancer after local therapy. Dose escalation occurred if a demethylating “response” [i.e. ≥10% decrease in peripheral blood mononuclear cell (PBMC) global 5meC content] was observed in <3 patients in cohort 1. Cohort 1 and 2 received disulfiram 250 mg and 500 mg daily respectively. The primary endpoint was the proportion of subjects with a demethylation response. Secondary endpoints included rate of PSA progression at 6 months, changes in PSA doubling time and safety/tolerability. Results Changes in global 5meC content were observed in 2 of 9 patients (22.2%) in cohort 1 and 3 of 10 (30.0%) in cohort 2. Only 5 subjects were on trial for ≥6 months, all were in cohort 1 and all had PSA progression by 6 months. No changes in PSA kinetics were observed in either cohort. Disulfiram was poorly tolerated with 6 patients experiencing grade 3 AEs (3 per cohort). Three of the responders displayed pre-treatment instability in their 5meC content. Conclusions A minority of patients had transient global PBMC demethylation changes. Instability in 5meC may limit the reproducibility of these findings, limiting our ability to confirm our hypothesis. Given the toxicities and no clinical benefits, further development of disulfiram should not be pursued in this population. PMID:23958896

  16. Liver protects metastatic prostate cancer from induced death by activating E-cadherin signaling.

    Science.gov (United States)

    Ma, Bo; Wheeler, Sarah E; Clark, Amanda M; Whaley, Diana L; Yang, Min; Wells, Alan

    2016-11-01

    Liver is one of the most common sites of cancer metastasis. Once disseminated, the prognosis is poor as these tumors often display generalized chemoresistance, particularly for carcinomas that derive not from the aerodigestive tract. When these cancers seed the liver, the aggressive cells usually undergo a mesenchymal to epithelial reverting transition that both aids colonization and renders the tumor cells chemoresistant. In vitro studies demonstrate that hepatocytes drive this phenotypic shift. However, the in vivo evidence and the molecular signals that protect these cells from induced death are yet to be defined. Herein, we report that membrane surface E-cadherin-expressing prostate cancer cells were resistant to cell death by chemotherapeutic drugs but E-cadherin null cells or those expressing E-cadherin only in the cytoplasm were sensitive to death signals and chemotherapies both in vitro and in vivo. While cell-cell E-cadherin ligandation reduced mitogenesis, this chemoprotection was proliferation-independent as killing of both 5-ethynyl-2'-deoxyuridine-positive (or Ki67(+) ) and 5-ethynyl-2'-deoxyuridine-negative (Ki67(-) ) cells was inversely related to membrane-bound E-cadherin. Inhibiting the canonical survival kinases extracellular signal-regulated protein kinases, protein kinase B, and Janus kinase, which are activated by chemotherapeutics in epithelial cell-transitioned prostate cancer, abrogated the chemoresistance both in cell culture and in animal models of metastatic cancer. For disseminated tumors, protein kinase B disruption in itself had no effect on tumor survival but was synergistic with chemotherapy, leading to increased killing.

  17. Improving radionuclide therapy in prostate cancer patients with metastatic bone pain

    OpenAIRE

    2009-01-01

    Bone seeking radiopharmaceuticals are indicated in cancer patients with multiple painful skeletal metastases. The majority of these patients are hormone-refractory prostate cancer patients in an advanced stage of their disease. Bone seeking radiopharmaceuticals relieve pain and improve the patients quality of life. The mostly used radiopharmaceuticals are 89SrCl2 (Metastron), 153Sm-EDTMP (Quadramet) and 186Re-HEDP. Differences between 89SrCl2, 153Sm-EDTMP and 186Re-HEDP were investigated. It ...

  18. Improving quality of life in patients with advanced cancer: Targeting metastatic bone pain

    OpenAIRE

    von Moos, Roger; Costa, Luis; Ripamonti, Carla Ida; Niepel, Daniela; Santini, Daniele

    2017-01-01

    Metastatic bone disease in patients with advanced cancer is frequently associated with skeletal complications. These can be debilitating, causing pain, impaired functioning and decreased quality of life, as well as reduced survival. This review considers how the management of metastatic bone pain might be optimised, to limit the considerable burden it can impose on affected patients. Cancer-related pain is notoriously under-reported and under-treated, despite the availability of many therapeu...

  19. Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

    OpenAIRE

    Pivot, X; Raymond, E; Laguerre, B.; Degardin, M; Cals, L; Armand, J P; Lefebvre, J L; Gedouin, D; Ripoche, V; Kayitalire, L; Niyikiza, C; Johnson, R.; Latz, J.; Schneider, M.

    2001-01-01

    This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m2 administered as a 10-minute infusi...

  20. Current paradigms and evolving concepts in metastatic castration-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Snmanta Krnmar Pal; Oliver Sartor

    2011-01-01

    @@ Until recently,docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC).The past year and a half has been marked by unprecedented progress in treatments for this disease.Three positive phase III clinical trials have emerged,each evaluating agents (sipuleucel-T,cabazitaxel and abiraterone)with distinct mechanisms of action.Herein,the three pivotal trials are described alongside both past and current large phase III studies conducted in this mCRPC.The overall survival for patients with mCRPC treated in current clinical trials is considerably longer than noted in the past.We note that more recent trials with older agents have also shown improved survival and discuss potential non-therapeutic biases that influence this critical measure of outcome.The necessity for utilizing randomized trials when evaluating new therapeutics is emphasized given the changing prognosis in this mCRPC.

  1. Energy balance in patients with advanced NSCLC, metastatic melanoma and metastatic breast cancer receiving chemotherapy--a longitudinal study.

    Science.gov (United States)

    Harvie, M N; Howell, A; Thatcher, N; Baildam, A; Campbell, I

    2005-02-28

    Chemotherapy exerts a variable effect on nutritional status. It is not known whether loss of body fat or fat-free mass (FFM) during chemotherapy relates to diminished dietary intake, failure to meet elevated energy requirements, or to the presence of an acute-phase response. We sought to determine prospective measurements of body mass and composition, resting energy expenditure, energy and protein intake, and C-reactive protein over a course of chemotherapy in 82 patients with advanced cancer. There was a large dropout from the study. Prospective measurements were obtained in 19 patients with non-small-cell lung cancer (NSCLC), 12 with metastatic melanoma and 10 with metastatic breast cancer. There were significant increases in energy intake among patients with metastatic breast cancer, 873 (266-1480) kJ (mean 95% CI; Pcancer patients gained percentage body fat over the course of treatment, 2.1 (0.8-3.5%). Gain or loss of body fat correlated to mean energy intake throughout chemotherapy in patients with NSCLC (Rs=0.751; Pcancer (Rs=0.617; Pcancer and NSCLC, but did not prevent loss of FFM in these groups.

  2. COX2 genetic variation, NSAIDs, and advanced prostate cancer risk.

    Science.gov (United States)

    Cheng, I; Liu, X; Plummer, S J; Krumroy, L M; Casey, G; Witte, J S

    2007-08-20

    Collective evidence suggests that cyclooxygenase 2 (COX2) plays a role in prostate cancer risk. Cyclooxygenase 2 is the major enzyme that converts arachidonic acid to prostaglandins, which are potent mediators of inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzymatic activity of COX2 and long-term use of NSAIDs appears to modestly lower the risk of prostate cancer. We investigated whether common genetic variation in COX2 influences the risk of advanced prostate cancer. Nine single-nucleotide polymorphisms (SNPs) in COX2 were genotyped among 1012 men in our case-control study of advanced prostate cancer. Gene-environment interactions between COX2 polymorphisms and NSAID use were also evaluated. Information on NSAID use was obtained by questionnaire. Three SNPs demonstrated nominally statistically significant associations with prostate cancer risk, with the most compelling polymorphism (rs2745557) associated with a lower risk of disease (odds ratio (OR) GC vs GG=0.64; 95% confidence interval (CI): 0.49-0.84; P=0.002). We estimated through permutation analysis that a similarly strong result would occur by chance 2.7% of the time. Nonsteroidal anti-inflammatory drug use was associated with a lower risk of disease in comparison to no use (OR=0.67; 95% CI: 0.52-0.87). No significant statistical interaction between NSAID use and rs2745557 was observed (P=0.12). Our findings suggest that variation in COX2 is associated with prostate cancer risk.

  3. Massive Bleeding as the First Clinical Manifestation of Metastatic Prostate Cancer due to Disseminated Intravascular Coagulation with Enhanced Fibrinolysis

    Science.gov (United States)

    Lopes, João Madeira; Victorino, Rui M. M.; Meneses Santos, João

    2016-01-01

    Disseminated intravascular coagulation (DIC) is the most frequent coagulation disorder associated with metastatic prostate adenocarcinoma. However, DIC with enhanced fibrinolysis as an initial presentation of prostate cancer is extremely rare. The appropriate treatment to control bleeding in these situations is challenging, controversial, and based on isolated case reports in the literature. A 66-year-old male presented at the emergency department with acute severe spontaneous ecchymoses localized to the limbs, laterocervical hematoma, and hemothorax. Prostate specific antigen level was 385 μg/L, bone scintigraphy revealed multiple bone metastases, and prostate biopsy confirmed adenocarcinoma (Gleason 9; 4 + 5). Laboratory investigation showed a pattern of enhanced fibrinolysis rather than the more common intravascular coagulation mechanism. Epsilon aminocaproic acid in monotherapy was initiated with a clear and rapid control of bleeding manifestations. This rare case of massive bleeding due to DIC with enhanced fibrinolysis as the first manifestation of prostate cancer suggests that in selected cases where the acute bleeding dyscrasia is clearly associated with a dominant fibrinolysis mechanism it is possible to use an approach of monotherapy with antifibrinolytics. PMID:27803823

  4. Cardiac glycosides stimulate Ca2+ increases and apoptosis in androgen-independent, metastatic human prostate adenocarcinoma cells.

    Science.gov (United States)

    McConkey, D J; Lin, Y; Nutt, L K; Ozel, H Z; Newman, R A

    2000-07-15

    Cardiac glycosides are used clinically to increase contractile force in patients with cardiac disorders. Their mechanism of action is well established and involves inhibition of the plasma membrane Na+/K+-ATPase, leading to alterations in intracellular K+ and Ca(2+) levels. Here, we report that the cardiac glycosides oleandrin, ouabain, and digoxin induce apoptosis in androgen-independent human prostate cancer cell lines in vitro. Cell death was associated with early release of cytochrome c from mitochondria, followed by proteolytic processing of caspases 8 and 3. Oleandrin also promoted caspase activation, detected by cleavage poly(ADP-ribose) polymerase and hydrolysis of a peptide substrate (DEVD-pNA). Comparison of the rates of apoptosis in poorly metastatic PC3 M-Pro4 and highly metastatic PC3 M-LN4 subclones demonstrated that cell death was delayed in the latter because of a delay in mitochondrial cytochrome c release. Single-cell imaging of intracellular Ca(2+) fluxes demonstrated that the proapoptotic effects of the cardiac glycosides were linked to their abilities to induce sustained Ca(2+) increases in the cells. Our results define a novel activity for cardiac glycosides that could prove relevant to the treatment of metastatic prostate cancer.

  5. Advances in diagnosis and treatment of metastatic cervical cancer.

    Science.gov (United States)

    Li, Haoran; Wu, Xiaohua; Cheng, Xi

    2016-07-01

    Cervical cancer is one of the most common cancers in women worldwide. The outcome of patients with metastatic cervical cancer is poor. We reviewed the relevant literature concerning the treatment and diagnosis of metastatic cervical cancer. There are two types of metastasis related to different treatments and survival rates: hematogenous metastasis and lymphatic metastasis. Patients with hematogenous metastasis have a higher risk of death than those with lymphatic metastasis. In terms of diagnosis, fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) and PET-computed tomography are effective tools for the evaluation of distant metastasis. Concurrent chemoradiotherapy and subsequent chemotherapy are well-tolerated and efficient for lymphatic metastasis. As for lung metastasis, chemotherapy and/or surgery are valuable treatments for resistant, recurrent metastatic cervical cancer and chemoradiotherapy may be the optimal choice for stage IVB cervical cancer. Chemotherapy and bone irradiation are promising for bone metastasis. A better survival is achieved with multimodal therapy. Craniotomy or stereotactic radiosurgery is an optimal choice combined with radiotherapy for solitary brain metastases. Chemotherapy and palliative brain radiation may be considered for multiple brain metastases and other organ metastases.

  6. Safety and chemopreventive effect of Polyphenon E in preventing early and metastatic progression of prostate cancer in TRAMP mice.

    Science.gov (United States)

    Kim, Seung Joon; Amankwah, Ernest; Connors, Shahnjayla; Park, Hyun Y; Rincon, Maria; Cornnell, Heather; Chornokur, Ganna; Hashim, Arig Ibrahim; Choi, Junsung; Tsai, Ya-Yu; Engelman, Robert W; Kumar, Nagi; Park, Jong Y

    2014-04-01

    Prostate cancer treatment is often accompanied by untoward side effects. Therefore, chemoprevention to reduce the risk and inhibit the progression of prostate cancer may be an effective approach to reducing disease burden. We investigated the safety and efficacy of Polyphenon E, a green tea extract, in reducing the progression of prostate cancer in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. A total of 119 male TRAMP and 119 C57BL/6J mice were treated orally with one of 3 doses of Polyphenon E (200, 500, and 1,000 mg/kg/day) in drinking water ad libitum replicating human achievable doses. Baseline assessments were performed before treatments. Safety and efficacy assessments during treatments were performed when mice were 12, 22, and 32 weeks old. The number and size of tumors in treated TRAMP mice were significantly decreased compared with untreated animals. In untreated 32 weeks old TRAMP mice, prostate carcinoma metastasis to distant sites was observed in 100% of mice (8/8), compared with 13% of mice (2/16) treated with high-dose Polyphenon E during the same period. Furthermore, Polyphenon E treatment significantly inhibited metastasis in TRAMP mice in a dose-dependent manner (P = 0.0003). Long-term (32 weeks) treatment with Polyphenon E was safe and well tolerated with no evidence of toxicity in C57BL/6J mice. Polyphenon E is an effective chemopreventive agent in preventing the progression of prostate cancer to metastasis in TRAMP mice. Polyphenon E showed no toxicity in these mouse models. Our findings provide additional evidence for the safety and chemopreventive effect of Polyphenon E in preventing metastatic progression of prostate cancer.

  7. The predictive value of ERG protein expression for development of castration-resistant prostate cancer in hormone-naïve advanced prostate cancer treated with primary androgen deprivation therapy

    DEFF Research Database (Denmark)

    Berg, Kasper Drimer; Røder, Martin A; Thomsen, Frederik B;

    2015-01-01

    BACKGROUND: Biomarkers predicting response to primary androgen deprivation therapy (ADT) and risk of castration-resistant prostate cancer (CRPC) is lacking. We aimed to analyse the predictive value of ERG expression for development of CRPC. METHODS: In total, 194 patients with advanced and....../or metastatic prostate cancer (PCa) treated with first-line castration-based ADT were included. ERG protein expression was analysed in diagnostic specimens using immunohistochemistry (anti-ERG, EPR3864). Time to CRPC was compared between ERG subgroups using multiple cause-specific Cox regression stratified...

  8. Enzalutamide as a second generation antiandrogen for treatment of advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Semenas J

    2013-08-01

    Full Text Available Julius Semenas,1 Nishtman Dizeyi,2 Jenny Liao Persson1 1Division of Experimental Cancer Research, Department of Laboratory Medicine, Lund University, Clinical Research Centre, Malmö, Sweden; 2Division of Urological Research, Department of Clinical Science, Lund University, Clinical Research Centre, Malmö, Sweden Abstract: Prostate cancer (PCa is the most common malignancy, and the third leading cancer-related cause of death among men of the Western world. Upon PCa progression into metastatic disease, androgen deprivation therapy is applied as the first-line treatment, and has been shown to be effective in most patients, leading to a decrease in serum prostate-specific antigen and relief of disease-related symptoms. However, advanced PCa almost inevitably progresses to a castration-resistant state, and is currently regarded as incurable. The large body of evidence indicates that PCa cells remain dependent on androgen receptor (AR signaling even in an androgen-deprived environment. As such, development of drugs that target AR and AR signaling pathways have become one of the major milestones in treatment of castration-resistant PCa (CRPC. Nevertheless, currently available therapies that target AR signaling are still regarded as palliative and more potent therapies are in great need. Over the past few years, a wide range of novel therapies has entered clinical trial for treatment of CRPC, including androgen synthesis inhibitors (abiraterone acetate, chemotherapeutic agents (docetaxel and cabazitaxel, and immunotherapies (sipuleucel-T. In this context, enzalutamide (previously referred to as MDV3100 is a novel second generation antiandrogen that has been demonstrated to significantly improve survival in men with metastatic CRPC in several clinical trials. In this paper we summarize recently completed and ongoing clinical trials of enzalutamide, and briefly discuss the efficacy of the novel antiandrogen therapy and its limitations for treatment of

  9. Characterization of a rat model of metastatic prostate cancer bone pain

    Directory of Open Access Journals (Sweden)

    Paolo Donato De Ciantis

    2010-11-01

    Full Text Available Paolo Donato De Ciantis1, Kiran Yashpal2, James Henry3, Gurmit Singh11Department of Pathology and Molecular Pathology, 2Pain Research Laboratories, 3Department of Psychiatry and Behavioral Neurosciences, McMaster University, Hamilton, Ontario, CanadaPurpose: The objectives of this study were to establish and characterize a novel animal model of metastatic prostate cancer-induced bone pain.Methods: Copenhagen rats were injected with 106 MATLyLu (MLL prostate cancer cells or phosphate-buffered saline by per cutaneous intra femoral injections into the right hind leg distal epiphysis. Over 13 days, rats progressively developed a tumor within the distal femoral epiphysis. On days 3, 7, 10, and 13 post injection, rats were subjected to the incapacitance and Randall–Selitto behavioral tests as they are believed to be indirect reflections of tumor induced pain. Ipsilateral hind limbs were subjected to X-ray and computed tomography (CT scans and histological sections were stained with hematoxylin and eosin (H&E.Results: Intra femoral injections of MLL cells resulted in the progressive development of a tumor leading to bone destruction and nociceptive behaviors. Tumor development resulted in the redistribution of weight to the contralateral hind leg and significantly reduced the paw withdrawal threshold of the ipsilateral hind paw as observed via the incapacitance and Randall–Selitto tests, respectively. X-ray and computed tomography scans along with H&E stains indicated tumor-associated structural damage to the distal femur. This model was challenged with administration of meloxicam. Compared with vehicle-injected controls, the meloxicam-treated rats displayed smaller nociceptive responses as observed with the incapacitance and Randall–Selitto tests, suggesting that meloxicam was effective in reducing the pain-related symptoms displayed by model animals and that the model behaved in a predictable way to cyclooxygenase-2 treatment.Conclusions: This

  10. Combined hormonal deprivation and radiotherapy in non-metastatic cancer of prostate; Hormono-radiotherapie des cancers de la prostate non metastatiques

    Energy Technology Data Exchange (ETDEWEB)

    Richaud, P. [Institut Bergonie, Centre Regional de Lutte Contre le Cancer, Service de Radiotherapie, 33 - Bordeaux (France); Mazeron, J.J. [Hopital Pitie-Salpetriere, Centre des Tumeurs, Service de Radiotherapie, 75 - Paris (France)

    2002-05-01

    Patients presenting with non-metastatic cancer of prostate have a high probability of relapse if they are treated by either surgery alone or irradiation alone, when poor prognosis factors are present. Clinical stage ({>=}T3a), Gleason score, and PSA level ({>=}20 ng/mL) are the more significant factors. It is likely that many patients can draw benefit of combined androgenic suppression and radiotherapy. However, despite results of European and American trials published the last decade, a number of questions remain without a clear response, especially on the modalities of treatment according to the characteristics of the disease. (author)

  11. Multifocal septic osteomyelitis mimicking skeletal metastatic disease in a patient with prostate cancer.

    Science.gov (United States)

    Alexiou, Evangelos; Georgoulias, Panagiotis; Valotassiou, Varvara; Georgiou, Evangelia; Fezoulidis, Ioannis; Vlychou, Marianna

    2015-01-01

    We present an unusual case of a 59 years old patient with prostate cancer, who was referred to our hospital with pleurodenia, low back and other sites of bone ostalgia, for bone scintiscan. The patient underwent a whole body bone scanning after the intravenous administration of 740MBq (99m)Tc-methylene diphosphonate (MDP). The main findings of the study were: increased radiotracer uptake at the T5, T9-T10 vertebrae, the head of the 11th rib and the area of the left sternoclavicular joint (SCJ), which were initially attributed to skeletal metastatic lesions. Another "hot" area in the left knee, was consistent with severe arthritis. Physical examination revealed fever up to 38.7°C, tenderness and swelling of his left knee and various painful sites. Due to persistent fever and markedly raised inflammatory markers (ESR 102mm/h, CRP 73.8mg/L, WBC 16.800 cells/μ L - neutrophils 78%, lymphocytes 15%, monocytes 5%, eosinophils 1%), the patient was further referred for a magnetic resonance (MR) scan with specific interest on the thoracic spine and the SCJ. In the sagittal short-tau inversion recovery (STIR) MR image, abnormally high signal involving both T9 and T10 vertebral bodies due to bone marrow oedema and irregularity of the endplates with focal destruction areas, were observed. The T9-T10 intervertebral disc had an abnormally high signal suggestive of "hot disc" sign and also a prevertebral soft tissue mass abutting the anterior aspect of the involved vertebral bodies. The axial T1-weighted image with fat saturation post gadolinium (Gd), revealed diffuse strong enhancement in the vertebral body, the paraspinal soft tissue mass and the adjacent right rib. Circumferential epidural enhancement indicative of intra-canal spread of the infection, was also noticed. Additional MR sequences covered the level of the SCJ. Extensive subarticular and soft tissue changes with fluid collection and bone oedema of the left SCJ were shown with the typical pattern of diffuse

  12. Incidence of high chromogranin A serum levels in patients with non metastatic prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Barnabei Agnese

    2010-12-01

    Full Text Available Abstract Background ChromograninA in prostate carcinoma (PC indicate NE differentiation. This tumour is more aggressive and resistant to hormone therapy. Patients and methods We analyzed the incidence of pre-operative ChromograninA serum levels in non metastatic PC patients. Serum PSA and ChromograninA were analyzed before treatment. Clinicopathological parameters were evaluated in relation to serum ChromograninA. 486 patients were enrolled. Results We found 352 pT2 and 134 pT3. 21 patients were N+. 278 patients had Gleason score levels 7. Median PSA pre-operative level was 7.61 ng/ml. PSA was significantly associated with pT stage (pT2 with PSA abnormal 23.6% vs pT3 48.5%, p 7 vs 29.5% in the Gleason score = 7 vs 27.3% in the Gleason score 7 (31.4% (p = 0.12. The serum ChromograninA levels in the two groups of patients were subdivided before and after 2005 on the basis of different used assays, showing no correlation with serum ChromograninA and other parameters. Conclusions This study showed that ChromograninA levels correlated to NE differentiation and possible aggressiveness of PC. Pre-operative circulating ChromograninA could complement PSA in selecting more aggressive PC cases, particularly in the presence of a higher Gleason score. Complementary information is provided by the absence of a correlation between serum ChromograninA and PSA levels.

  13. A survival score for patients with metastatic spinal cord compression from prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rades, D.; Douglas, S. [Luebeck Univ. (Germany). Dept. of Radiation Oncology; Veninga, T. [Dr. Bernard Verbeeten Institute Tilburg (Netherlands). Dept. of Radiation Oncology; Bajrovic, A. [University Medical Center Hamburg-Eppendorf (Germany). Dept. of Radiation Oncology; Stalpers, L.J.A. [Academic Medical Center Amsterdam (Netherlands). Dept. of Radiotherapy; Hoskin, P.J. [Mount Vernon Center for Cancer Treatment, Northwood (United Kingdom). Dept. of Clinical Oncology; Rudat, V. [Saad Specialist Hospital Al-Khobar (Saudi Arabia). Dept. of Radiation Oncology; Schild, S.E. [Mayo Clinic Scottsdale, AZ (United States). Dept. of Radiation Oncology

    2012-09-15

    Background: This study aimed to develop and validate a survival scoring system for patients with metastatic spinal cord compression (MSCC) from prostate cancer. Patients and methods: Of 436 patients, 218 patients were assigned to the test group and 218 patients to the validation group. Eight potential prognostic factors (age, performance status, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits) plus the fractionation regimen were retrospectively investigated for associations with survival. Factors significant in the multivariate analysis were included in the survival score. The score for each significant prognostic factor was determined by dividing the 6-month survival rate (%) by 10. The total score represented the sum of the scores for each factor. The prognostic groups of the test group were compared to the validation group. Results: In the multivariate analysis of the test group, performance status, ambulatory status, other bone metastases, visceral metastases, and interval from cancer diagnosis to radiotherapy were significantly associated with survival. Total scores including these factors were 20, 21, 22, 24, 26, 28, 29, 30, 31, 32, 33, 35, 37, or 39 points. In the test group, the 6-month survival rates were 6.5% for 20-24 points, 44.6% for 26-33 points, and 95.8% for 35-39 points (p < 0.0001). In the validation group, the 6-month survival rates were 7.4%, 45.4%, and 94.7%, respectively (p < 0.0001). Conclusions: Because the survival rates of the validation group were almost identical to the test group, this score can be considered valid and reproducible. (orig.)

  14. Use of prednisone with abiraterone acetate in metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Auchus, Richard J; Yu, Margaret K; Nguyen, Suzanne; Mundle, Suneel D

    2014-12-01

    Abiraterone acetate, a prodrug of the CYP17A1 inhibitor abiraterone that blocks androgen biosynthesis, is approved for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) in combination with prednisone or prednisolone 5 mg twice daily. This review evaluates the basis for the effects of prednisone on mineralocorticoid-related adverse events that arise because of CYP17A1 inhibition with abiraterone. Coadministration with the recommended dose of glucocorticoid compensates for abiraterone-induced reductions in serum cortisol and blocks the compensatory increase in adrenocorticotropic hormone seen with abiraterone. Consequently, 5 mg prednisone twice daily serves as a glucocorticoid replacement therapy when coadministered with abiraterone acetate, analogous to use of glucocorticoid replacement therapy for certain endocrine disorders. We searched PubMed to identify safety concerns regarding glucocorticoid use, placing a focus on longitudinal studies in autoimmune and inflammatory diseases and cancer. In general, glucocorticoid-related adverse events, including bone loss, immunosuppression, hyperglycemia, mood and cognitive alterations, and myopathy, appear dose related and tend to occur at doses and/or treatment durations greater than the low dose of glucocorticoid approved in combination with abiraterone acetate for the treatment of mCRPC. Although glucocorticoids are often used to manage tumor-related symptoms or to prevent treatment-related toxicity, available evidence suggests that prednisone and dexamethasone might also offer modest therapeutic benefit in mCRPC. Given recent improvements in survival achieved for mCRPC with novel agents in combination with prednisone, the risks of these recommended glucocorticoid doses must be balanced with the benefits shown for these regimens.

  15. Pleuropulmonary and Lymph Node Progression after Docetaxel - Benefits from Treatment with Cabazitaxel in Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Angel Segura Huerta

    2013-07-01

    Full Text Available Introduction: To date, there are no guidelines for a rational and more favourable sequence of treatment after docetaxel. Two drugs (cabazitaxel and abiraterone have recently been approved as second-line treatment after docetaxel failure in metastatic castration-resistant prostate cancer (mCRPC, but there are no studies comparing abiraterone versus cabazitaxel. The most suitable drug is chosen based on the physician's opinion and the patient's characteristics. In patients with a good performance status who are able to receive either treatment, it would be convenient to begin with cabazitaxel and to reserve abiraterone in case there is a worsening of the general status, in consideration of abiraterone's more favourable toxicity profile. Case Report: We describe the case of a 74-year-old male with mCRPC who presented with an interesting and uncommon tumour dissemination (pleuropulmonary occurring after the first standard treatment with docetaxel. Intravenous treatment with cabazitaxel 25 mg/m2 and oral prednisone 10 mg continuously was initiated. The patient received a total of 8 cycles of chemotherapy. A reduction of mediastinal adenopathies and infrarenal para-aortic stable bone involvement and an absence of pleural effusion were observed. No relevant toxicity was noted. Since February 2012, a progressive PSA increase without clinical deterioration has been noted. Conclusions: The selection criteria for second- and third-line systemic treatment and the excellent response obtained with cabazitaxel in an unusual disease setting are described. The results confirm the long duration and quality of response of cabazitaxel treatment. Further therapeutic options in this group of patients are suggested.

  16. Combination of rapamycin, CI-1040, and 17-AAG inhibits metastatic capacity of prostate cancer via Slug inhibition.

    Directory of Open Access Journals (Sweden)

    Guanxiong Ding

    Full Text Available Though prostate cancer (PCa has slow progression, the hormone refractory (HRCP and metastatic entities are substantially lethal and lack effective treatments. Transcription factor Slug is critical in regulating metastases of various tumors including PCa. Here we studied targeted therapy against Slug using combination of 3 drugs targeting 3 pathways respectively converging via Slug and further regulating PCa metastasis. Using in vitro assays we confirmed that Slug up-regulation incurred inhibition of E-cadherin that was anti-metastatic, and inhibited Bim-regulated cell apoptosis in PCa. Upstream PTEN/Akt, mTOR, Erk, and AR/Hsp90 pathways were responsible for Slug up-regulation and each of these could be targeted by rapamycin, CI-1040, and 17-AAG respectively. In 4 PCa cell lines with different traits in terms of PTEN loss and androgen sensitivity we tested the efficacy of mono- and combined therapy with the drugs. We found that metastatic capacity of the cells was maximally inhibited only when all 3 drugs were combined, due to the crosstalk between the pathways. 17-AAG decreases Slug expression via blockade of HSP90-dependent AR stability. Combination of rapamycin and CI-1040 diminishes invasiveness more potently in PCa cells that are androgen insensitive and with PTEN loss. Slug inhibited Bim-mediated apoptosis that could be rescued by mTOR/Erk/HSP90 inhibitors. Using mouse models for circulating PCa DNA quantification, we found that combination of mTOR/Erk/HSP90 inhibitors reduced circulating PCa cells in vivo significantly more potently than combination of 2 or monotherapy. Conclusively, combination of mTOR/Erk/Hsp90 inhibits metastatic capacity of prostate cancer via Slug inhibition.

  17. Risk Factors for Metastatic Castration-Resistant Prostate Cancer (CRPC) Predict Long-Term Treatment with Docetaxel

    OpenAIRE

    Kawahara, Takashi; Miyoshi, Yasuhide; Sekiguchi, Zenkichi; Sano, Futoshi; Hayashi, Narihiko; Teranishi, Jun-ichi; Misaki, Hiroshi; Noguchi, Kazumi; Kubota, Yoshinobu; Uemura, Hiroji

    2012-01-01

    Purpose For patients with metastatic castration-resistant prostatic cancer (mCRPC), docetaxel plus prednisone leads to superior survival and a higher response rate compared with mitoxantrone plus prednisone. We analyzed the efficacy of long-term treatment with ≥10 cycles of docetaxel, and validated the risk group classification in predicting overall survival (OS) in Japanese patients with mCRPC. Patients and Methods Fifty-two patients with mCRPC were administered 55 mg/m2 docetaxel and 8 mg d...

  18. Further analysis of PREVAIL: Enzalutamide use in chemotherapy-naïve men with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Jeanny B Aragon-Ching

    2014-12-01

    Full Text Available PREVAIL was a phase III multinational, double-blind, placebo-controlled trial that enrolled chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC, which showed remarkable improvement in co-primary endpoints with an overall 81% reduction in the risk of radiographic progression, as well as 29% reduction in the risk of death in favor of the enzalutamide arm over placebo. All secondary endpoints including time to subsequent chemotherapy initiation and prostate specific antigen (PSA progression were in favor of the enzalutamide arm. The results of PREVAIL shows the utility of enzalutamide that would likely soon expand the indication to asymptomatic or minimally symptomatic men with mCRPC not previously treated with chemotherapy.

  19. Evolving landscape and novel treatments in metastatic castrate-resistant prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Paul J Toren; Martin E Gleave

    2013-01-01

    Treatment options for castrate-resistant prostate cancer (CRPC) have advanced in recent years and significantly improved the outlook for patients with this aggressive and lethal disease.Further understanding of the biologyof CRPC has led to several new targeted therapies and continues to emphasize the importance of androgen receptor (AR) directed therapy.The treatment landscape is rapidly changing and further biologically rationale,biomarker-based ongoing clinical trials are needed.We review the recent results of major clinical trials in CRPC.New and investigational agents now in clinical evaluation are reviewed including inhibitors of angiogenesis,microtubules,chaperones,AR and intracellular kinases,as well as immunotherapy,radiopharmaceuticals and bone-targeted agents.The recent improvement in prognosis for CRPC brings continued optimism for further improvements.Thoughtful planning of clinical trials and further understanding of the mechanisms of resistance to therapies will allow for continued progress in patient care.

  20. Sustained complete response to CTLA-4 blockade in a patient with metastatic, castration-resistant prostate cancer.

    Science.gov (United States)

    Graff, Julie N; Puri, Sachin; Bifulco, Carlo B; Fox, Bernard A; Beer, Tomasz M

    2014-05-01

    We present the case of a man with metastatic, castration-resistant prostate cancer, who had a complete prostate-specific antigen (PSA) response after 2½ doses of ipilimumab. His treatment course was complicated by diarrhea and autoimmune hepatitis, both of which resolved within 4 months. Sera and biopsy specimens were accessed, and sera from pretreatment and day 113 were analyzed. Augmented antibody responses were detected against 11 potential tumor antigens, with responses ranging from 5- to 20-fold in day 113 sera compared with baseline. Genes that were targets of a strong antibody response (arbitrarily set at 10-fold or greater increase) were analyzed by real-time PCR for expression in the tumor biopsy cDNA. Of the top 5 genes, only 3-hydroxyisobutyryl-CoA hydrolase (HIBCH) could be identified in the amplified tumor biopsy cDNA. Using an antibody to HIBCH, immunohistochemical analysis documented strong expression of the protein. Together, these data suggest that an augmented antibody response to HIBCH, an antigen that was expressed by the patient's prostate cancer, could have contributed to the clinical response. After 16 months of PSA stability, he discontinued his androgen-suppression therapy. With the return of his testosterone, his PSA increased slightly, likely originating from his intact prostate. He has been disease free for the past 6 years without any additional therapy.

  1. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Bukowski RM

    2011-08-01

    Full Text Available Ronald M BukowskiCleveland Clinic Taussig Cancer Center, Cleveland Clinic Foundation, Cleveland, OH, USAAbstract: The management of renal cell carcinoma (RCC has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus, and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α. The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients

  2. Advanced Prostate Cancer Presenting as Hemolytic Uremic Syndrome

    Directory of Open Access Journals (Sweden)

    R. Ramos

    2013-01-01

    Full Text Available Introduction. Hemolytic uremic syndrome (HUS is characterized by endothelial dysfunction, consumption thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. HUS generally has a dismal prognosis, except when associated with gastroenteritis caused by verotoxin-producing bacteria. Cancer associated HUS is uncommon, and there are only scarce reports on prostate cancer presenting with HUS. Case Presentation. A 72-year-old man presented to the emergency department with oliguria, hematuria, and hematemesis. Clinical evaluation revealed acute renal failure, hemolysis, normal blood-clotting studies, and prostate-specific antigen value of 1000 ng/mL. The patient was started on hemodialysis, ultrafiltration with plasma exchange, and androgen blockade with bicalutamide and completely recovered from HUS. The authors review the 14 published cases on this association. Conclusion. The association of HUS and prostate cancer occurs more frequently in patients with high-grade, clinically advanced prostate cancer. When readily recognized and appropriately treated, HUS does not seem to worsen prognosis in prostate cancer patients.

  3. Exosomal ITGA3 interferes with non-cancerous prostate cell functions and is increased in urine exosomes of metastatic prostate cancer patients

    Directory of Open Access Journals (Sweden)

    Irene V. Bijnsdorp

    2013-10-01

    Full Text Available Background: Cancer cells are able to change the protein expression and behavior of non-cancerous surrounding cells. Exosomes, secreted by prostate cancer (PCa cells, may have a functional role in cancer metastasis and present a promising source for protein biomarkers. The aim of the present study was to identify which proteins in exosomes can influence non-cancerous cells, and to determine whether we can use urine exosomal proteins to identify high-risk PCa patients. Method: Exosomes were isolated by ultracentrifugation. Migration and invasion were studied by the transwell (invasion assay. Proteomics was performed by LC-MS/MS and identified proteins were validated by Western blotting. Cellular uptake of fluorescent labeled PKH67-exosomes was measured by FACS. Results: Based on comparative protein profiling by mass spectrometry-based proteomics of LNCaP- and PC3-exosomes, we selected ITGA3 and ITGB1, involved in migration/invasion, for further analyses. Inhibition of exosomal ITGA3 reduced the migration and invasion of non-cancerous prostate epithelial cells (prEC almost completely. Cellular uptake of exosomes by prEC was higher with PC3-exosomes compared to LNCaP exosomes. Finally, ITGA3 and ITGB1 were more abundant in urine exosomes of metastatic patients (p<0.05, compared to benign prostate hyperplasia or PCa. Conclusion: These data indicate exosomal ITGA3 and ITGB1 may play a role in manipulating non-cancerous surrounding cells and that measurement of ITGA3 and ITGB1 in urine exosomes has the potential to identify patients with metastatic PCa in a non-invasive manner.

  4. Critical appraisal of pazopanib as treatment for patients with advanced metastatic renal cell carcinoma.

    Science.gov (United States)

    Bukowski, Ronald M

    2011-01-01

    The management of renal cell carcinoma (RCC) has undergone significant changes during the past 10 years, with the treatment of metastatic RCC undergoing the most radical changes. These developments reflect an enhanced understanding of this tumor's underlying biology, which was then translated into the development of a new treatment paradigm. Current therapeutic approaches for the management of patients with metastatic RCC utilize knowledge of histology, molecular abnormalities, clinical prognostic factors, the natural history of this malignancy, and the treatment efficacy and toxicity of available agents. The treatment options available for patients with metastatic RCC have changed dramatically over the past 6 years. Interferon-α and interleukin-2 were the previous mainstays of therapy, but since December 2005, six new agents have been approved in the US for the treatment of advanced RCC. Three are multi-targeted tyrosine kinase inhibitors (TKI) including sunitinib, sorafenib, and pazopanib, two target the mammalian target of rapamycin (temsirolimus and everolimus), and one is a humanized monoclonal antibody (bevacizumab in combination with interferon-α). The current review focuses on the newest TKI available to treat patients with metastatic RCC, pazopanib. The development of this agent both preclinically and clinically is reviewed. The efficacy and safety data from the pivotal clinical trials are discussed, and the potential role of pazopanib in the treatment of patients with metastatic RCC in comparison to other treatment alternatives is critically appraised. This agent has a favorable overall risk benefit, and the available data demonstrate efficacy in patients with metastatic RCC who are either treatment-naïve or cytokine refractory. It therefore represents another alternative for treatment of metastatic RCC patients.

  5. Radium-223 chloride: a potential new treatment for castration-resistant prostate cancer patients with metastatic bone disease

    Directory of Open Access Journals (Sweden)

    Harrison MR

    2013-01-01

    Full Text Available Michael R Harrison, Terence Z Wong, Andrew J Armstrong, Daniel J GeorgeDuke Cancer Institute, Durham, NC, USABackground: Radium-223 chloride (223Ra; Alpharadin is an alpha-emitting radioisotope that targets areas of osteoblastic metastasis and is excreted by the small intestine. When compared with beta-emitters (eg, strontium-89, samarium-153, 223Ra delivers a high quantity of energy per track length with short tissue penetration.Objective: This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile.Methods: Data from clinical trials including abstracts were collected and reviewed using the PubMed Database, as well as the American Society of Clinical Oncology abstract database.Conclusion: Current bone-targeted therapies fall into two main categories: antiresorptive agents (eg, zoledronic acid, denosumab, which have been shown to delay skeletal-related events, and radiopharmaceuticals (eg, samarium-153, which may have a role in pain palliation. Historically, neither antiresorptive agents nor radiopharmaceuticals have shown definitive evidence of improved overall survival or other antitumor effects in metastatic castrate-resistant prostate cancer (mCRPC. Radiopharmaceuticals are limited by myelosuppresion, thrombocytopenia, and renal excretion. In a recently reported randomized Phase III trial in men with symptomatic bone-metastatic CRPC who had received or were ineligible for docetaxel chemotherapy, 223Ra treatment resulted in improved overall survival and delayed skeletal-related events. Toxicity consisted of minor gastrointestinal side effects and mild neutropenia and thrombocytopenia that were rarely severe. Pending regulatory approval, 223Ra may represent a unique and distinct option for an important subgroup of patients with mCRPC; future trials should address its use in combination or in sequence with existing and novel

  6. Vandetanib in locally advanced or metastatic differentiated thyroid cancer

    DEFF Research Database (Denmark)

    Leboulleux, Sophie; Bastholt, Lars; Krause, Thomas

    2012-01-01

    No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting.......No effective standard treatment exists for patients with radioiodine-refractory, advanced differentiated thyroid carcinoma. We aimed to assess efficacy and safety of vandetanib, a tyrosine kinase inhibitor of RET, VEGFR and EGFR signalling, in this setting....

  7. Changes of biochemical markers of bone turnover and YKL-40 following hormonal treatment for metastatic prostate cancer are related to survival

    DEFF Research Database (Denmark)

    Johansen, Julia S; Brasso, Klaus; Iversen, Peter;

    2007-01-01

    Elevated serum levels of biochemical markers of bone turnover and YKL-40 in patients with metastatic prostate cancer (PC) at the time of diagnosis are associated to poor prognosis. In this study, we evaluated the value of these biomarkers in monitoring the patients during hormonal treatment....

  8. Safety of cabazitaxel in senior adults with metastatic castration-resistant prostate cancer: results of the European compassionate-use programme

    NARCIS (Netherlands)

    Heidenreich, A.; Bracarda, S.; Mason, M.; Ozen, H.; Sengelov, L.; Oort, I.M. van; Papandreou, C.; Fossa, S.; Hitier, S.; Climent, M.A.

    2014-01-01

    BACKGROUND: Cabazitaxel/prednisone has been shown to prolong survival versus mitoxantrone/prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) that has progressed during or after docetaxel. Subsequently, compassionate-use programmes (CUPs) and expanded-access programme

  9. Randomized, Placebo-Controlled, Phase III Trial of Sunitinib Plus Prednisone Versus Prednisone Alone in Progressive, Metastatic, Castration-Resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Michaelson, M Dror; Oudard, Stephane; Ou, Yen-Chuan

    2014-01-01

    PURPOSE: We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg...

  10. Efficacy and Safety of Abiraterone Acetate in Elderly (75 Years or Older) Chemotherapy Naive Patients with Metastatic Castration Resistant Prostate Cancer

    NARCIS (Netherlands)

    Smith, M.R.; Rathkopf, D.E.; Mulders, P.F.A.; Carles, J.; Poppel, H. Van; Li, J.; Kheoh, T.; Griffin, T.W.; Molina, A.; Ryan, C.J.

    2015-01-01

    PURPOSE: Metastatic castration resistant prostate cancer primarily affects elderly men. In this post hoc analysis we investigated the safety and efficacy of abiraterone acetate in elderly (age 75 years or greater) and younger (less than 75 years) patient subgroups at the prespecified interim analysi

  11. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial

    DEFF Research Database (Denmark)

    de Bono, Johann Sebastian; Oudard, Stephane; Ozguroglu, Mustafa;

    2010-01-01

    Cabazitaxel is a novel tubulin-binding taxane drug with antitumour activity in docetaxel-resistant cancers. We aimed to compare the efficacy and safety of cabazitaxel plus prednisone with those of mitoxantrone plus prednisone in men with metastatic castration-resistant prostate cancer...

  12. Randomised study of Casodex 50 MG monotherapy vs orchidectomy in the treatment of metastatic prostate cancer. The Scandinavian Casodex Cooperative Group

    DEFF Research Database (Denmark)

    Iversen, P; Tveter, K; Varenhorst, E

    1996-01-01

    The effect of Casodex (ICI 176,334), a new, once-daily, selective antiandrogen, given as 50 mg monotherapy, was compared with orchidectomy in a randomised, multicentre, open study in 376 patients with metastatic prostate cancer. At 3 months, PSA was reduced by 86% in the Casodex group and by 96% ...

  13. Microenvironment-Programmed Metastatic Prostate Cancer Stem Cells (mPCSCs)

    Science.gov (United States)

    2015-10-01

    Lineage traced normal epithelium CSCs (cancer-propagating cells) Multilineage potential LDA & serial tumor transplantations Conditionally expressing...transformation, can initiate prostate cancer in immunodeficient mice (10). The authors developed a system whereby na€ve adult human prostate epithelium is...PSA, the most "important" molecule in defining the prostate as a male glandular organ and in defining fully differentiated luminal epithelial cells

  14. Sipuleucel-T (Provenge) autologous vaccine approved for treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer.

    Science.gov (United States)

    Gardner, Thomas A; Elzey, Bennett D; Hahn, Noah M

    2012-04-01

    Sipuleucel-T (Provenge) (Sip-T) is first -in class as a therapeutic autologous vaccine approved for the treatment of men with asymptomatic or minimally symptomatic castrate-resistant metastatic prostate cancer. This product is the culmination of decades of basic immunological and prostate cancer investigations and 13 y of clinical trial investigations. Sip-T represents a paradigm shift in cancer therapeutics and represents the first approved autologous therapeutic cancer vaccine, which has demonstrated a survival benefit. The potential benefit of this product is the excellent risk to benefit ratio, which will allow for the combination of this approach with other more toxic therapies. The favorable risk to benefit will also afford the opportunity for trials investigating this product earlier in the disease state and in combination with local therapies. The ability to target more localized or lower volume disease will maximize the therapeutic benefit over a longer period of time. The novelty of the platform of this approach could be used to treat any cancer with a tumor-specific cell surface target. The main product of Sip-T is the re-infusion of a patient's antigen presenting cells from leukapheresis after ex-vivo exposure to a chimeric protein of human GM-CSF and PAP. In metastatic CRPC patients three infusions of these activated cells over a month lead to statistically significant 4.1 mo increase in median survival and a 22.5% reduction in risk of death. The main side effect from this re-infusion of activated immune cells is a "flu-like" syndrome that includes chills, fatigue, fevers, back pain, nausea, joints aches and headaches in decreasing order of frequency. Immune monitoring during the clinical trials also demonstrated a specific cellular and antibody immune response, suggesting the proposed mechanism of adoptive immunotherapy to PAP was behind this survival benefit. This product also serves as a proof of principle for targeted immunotherapy for others

  15. Development of sipuleucel-T: autologous cellular immunotherapy for the treatment of metastatic castrate resistant prostate cancer.

    Science.gov (United States)

    Sims, Robert B

    2012-06-19

    Sipuleucel-T, the first autologous cellular immunotherapy approved by the United States Food and Drug Administration, is designed to stimulate an immune response to prostate cancer. Sipuleucel-T is manufactured by culturing a patient's peripheral blood mononuclear cells, including autologous antigen presenting cells (APCs), with a recombinant protein comprising a tumor-associated antigen (prostatic acid phosphatase [PAP]) and granulocyte colony-macrophage stimulating factor (GM-CSF). A full course of treatment comprises 3 infusions of sipuleucel-T, given at approximately 2-week intervals. The pattern of APC activation is consistent with priming by the first infusion, and boosting by the second and third infusions. Preclinical and clinical studies have demonstrated evidence of a robust antigen-specific immune response that includes a progressive and persistent increase in antigen-specific cellular and humoral immune responses. Treatment with sipuleucel-T has demonstrated a survival benefit in Phase 3 studies of subjects with metastatic castrate resistant (hormone refractory) prostate cancer (mCRPC). Adverse events with sipuleucel-T were generally mild to moderate and resolved within 2 days. Serious adverse events, autoimmune events, and cerebrovascular events occurred at a similar rate to control subjects. As the first autologous cellular immunotherapy to demonstrate an improvement in overall survival in asymptomatic or minimally symptomatic mCRPC patients, sipuleucel-T represents a new treatment paradigm in oncology.

  16. Adjuvant radiotherapy for pathologically advanced prostate cancer a randomized clinical trial

    Energy Technology Data Exchange (ETDEWEB)

    Ian, M.; Thompson, J.R.; Catherine, M.; Tangen, P.H.; Paradelo, J.; Scott Lucia, M.; Miller, G.; Troyer, D.; Messing, E.; Forman, J.; Chin, J.; Swanson, G.; Canby-Hagino, E.; Crawford, E.D

    2008-01-15

    Context - Despite a stage-shift to earlier cancer stages and lower tumor volumes for prostate cancer, pathologically advanced disease is detected at radical prostatectomy in 38% to 52% of patients. However, the optimal management of these patients after radical prostatectomy is unknown. Objective - To determine whether adjuvant radiotherapy improves metastasis-free survival in patients with stage pT3 NO MO prostate cancer. Design, Setting, and Patients - Randomized, prospective, multi-institutional, US clinical trial with enrollment between August 15, 1988, and January 1, 1997 (with database frozen for statistical analysis on September 21, 2005). Patients were 425 men with pathologically advanced prostate cancer who had undergone radical prostatectomy. Intervention - Men were randomly assigned to receive 60 to 64 Gy of external beam radiotherapy delivered to the prostatic fossa (n = 214) or usual care plus observation (n = 211). Main Outcome Measures - Primary outcome was metastasis-free survival, defined as time to first occurrence of metastatic disease or death due to any cause. Secondary outcomes included prostate-specific antigen (PSA) relapse, recurrence-free survival, overall survival, freedom from hormonal therapy, and postoperative complications. Results - Among the 425 men, median follow-up was 10.6 years (inter-quartile range, 9.2-12.7 years). For metastasis-free survival,76 (35.5%) of 214 men in the adjuvant radiotherapy group were diagnosed with metastatic disease or died (median metastasis-free estimate, 14.7 years), compared with 91 (43.1%) of 211 (median metastasis-free estimate, 13.2 years) of those in the observation group (hazard ratio [HR], 0.75; 95% CI, 0.55-1.02; P = .06). There were no significant between-group differences for overall survival (71 deaths, median survival of 14.7 years for radiotherapy vs 83 deaths, median survival of 13.8 years for observation; HR, 0.80; 95% Cl, 0.58-1.09; P =.16). PSA relapse (median PSA relapse-free survival

  17. Management Options in Advanced Prostate Cancer: What is the Role for Sipuleucel-T?

    Science.gov (United States)

    Bitting, Rhonda L; Armstrong, Andrew J; George, Daniel J

    2011-01-01

    Most prostate cancer-related deaths occur in patients with castration-resistant prostate cancer (CRPC). Until recently, only therapy with docetaxel and prednisone has been shown to prolong survival in men with metastatic CRPC. With the United States Food and Drug Administration (US FDA) approvals of sipuleucel-T, cabazitaxel, and abiraterone acetate, all based on improvement in overall survival, the landscape for management of men with metastatic CRPC has dramatically changed. In this review we will discuss the pivotal clinical trial data leading to these approvals, with particular focus on the unique indication for sipuleucel-T and the implications for optimal management and sequencing of treatment in this patient population.

  18. Zoladex plus flutamide vs. orchidectomy for advanced prostatic cancer. Danish Prostatic Cancer Group (DAPROCA)

    DEFF Research Database (Denmark)

    Iversen, P

    1990-01-01

    The study comprised 262 patients with previously untreated advanced carcinoma of the prostate. Patients were randomized either to undergo orchidectomy or to receive combined treatment with Zoladex, 3.6 mg every 4 weeks, plus flutamide, 250 mg t.i.d. At present the median follow-up is 39 months....... The objective response to therapy was better in the Zoladex plus flutamide group, but no differences in subjective response, time to disease progression, or survival have been demonstrated between the 2 groups. Adverse effects were more common in the Zoladex plus flutamide group. Thus, 'total androgen blockade......' with Zoladex plus flutamide was not clinically superior to orchidectomy in the treatment of patients with advanced prostatic cancer....

  19. Sipuleucel-T in patients with metastatic castration-resistant prostate cancer: an insight for oncologists

    OpenAIRE

    Garcia, Jorge A.

    2011-01-01

    Sipuleucel-T represents a novel immunotherapeutic compound designed to stimulate an immune response against castration-resistant prostate cancer (CRPC). Sipuleucel-T is an autologous active cellular immunotherapy product, which includes autologous dendritic cells pulsed ex vivo with PAP2024, a recombinant fusion protein made of prostatic acid phosphatase and granulocyte-macrophag...

  20. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer

    DEFF Research Database (Denmark)

    Brose, Marcia S; Nutting, Christopher M; Jarzab, Barbara

    2014-01-01

    BACKGROUND: Patients with radioactive iodine ((131)I)-refractory locally advanced or metastatic differentiated thyroid cancer have a poor prognosis because of the absence of effective treatment options. In this study, we assessed the efficacy and safety of orally administered sorafenib...... in the treatment of patients with this type of cancer. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 3 trial (DECISION), we investigated sorafenib (400 mg orally twice daily) in patients with radioactive iodine-refractory locally advanced or metastatic differentiated thyroid...... cancer. Adverse events were consistent with the known safety profile of sorafenib. These results suggest that sorafenib is a new treatment option for patients with progressive radioactive iodine-refractory differentiated thyroid cancer. FUNDING: Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals...

  1. Prostate specific membrane antigen- a target for imaging and therapy with radionuclides

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Choyke, Peter L; Capala, Jacek

    2010-01-01

    Prostate cancer continues to represent a major health problem, and yet there is no effective treatment available for advanced metastatic disease. Thus, there is an urgent need for the development of more effective treatment modalities that could improve the outcome. Because prostate specific...... to become both diagnostic and/or therapeutic agents. The use of PSMA binding agents, labelled with diagnostic and therapeutic radio-isotopes, opens up the potential for a new era of personalized management of metastatic prostate cancer....

  2. Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer.

    Science.gov (United States)

    Wan, Fangning; Qin, Xiaojian; Zhang, Guiming; Lu, Xiaolin; Zhu, Yao; Zhang, Hailiang; Dai, Bo; Shi, Guohai; Ye, Dingwei

    2015-05-01

    Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including β-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.

  3. Human epidermal growth factor receptor type 2 protein expression in Chinese metastatic prostate cancer patients correlates with cancer specific survival and increases after exposure to hormonal therapy

    Institute of Scientific and Technical Information of China (English)

    Bo Dai; Yun-Yi Kong; Ding-Wei Ye; Chun-Guang Ma; Xiao-Yan Zhou; Xu-Dong Yao

    2008-01-01

    Aim: To investigate human epidermal growth factor receptor type 2 (HER2) protein expression and gene amplification in Chinese metastatic prostate cancer patients and their potential value as prognostic factors. Methods: Immuno-histochemistry (IHC) was performed to investigate HER2 protein expression in prostate biopsy specimens from 104 Chinese metastatic prostate cancer patients. After 3-11 months of hormonal therapy, 12 patients underwent transure- thral resection of the prostate (TURP). HER2 protein expression of TURP specimens was compared with that of the original biopsy specimens. Of these, 10 biopsy and 4 TURP specimens with HER2 IHC staining scores ≥ 2+ were investigated for HER2 gene amplification status by fluorescent in situ hybridization (FISH). Results: Of the 104 prostate biopsy specimens, HER2 protein expression was 0, 1+, 2+ and 3+ in 49 (47.1%), 45 (43.3%), 8 (7.7%) and 2 (1.9%) cases, respectively. There was a significant association between HER2 expression and Gleason score (P = 0.026). HER2 protein expression of prostate cancer tissues increased in 33.3% of patients after hormonal therapy. None of the 14 specimens with HER2 IHC scores > 2+ showed HER2 gene amplification. Patients with HER2 scores ≥ 2+ had a significantly higher chance of dying from prostate cancer than those with HER2 scores of 0 (P = 0.004) and 1+ (P = 0.034). Multivariate Cox regression analysis showed that HER2 protein expression intensity was an independent predictor of cancer-related death (P = 0.039). Conclusion: An HER2 IHC score ≥ 2+ should be defined as HER2 protein overexpression in prostate cancer. Overexpression of HER2 protein in cancer tissue might suggest an increased risk of dying from prostate cancer. HER2 protein expression increases in some individual patients after hormonal therapy.

  4. Avascular Necrosis of the Femoral Head After Palliative Radiotherapy in Metastatic Prostate Cancer: Absence of a Dose Threshold?

    Science.gov (United States)

    Daoud, Alia M; Hudson, Mack; Magnus, Kenneth G; Huang, Fleur; Danielson, Brita L; Venner, Peter; Saluja, Ronak; LeGuerrier, Bronwen; Daly, Helene; Emmenegger, Urban; Fairchild, Alysa

    2016-03-06

    Avascular necrosis (AVN) is the final common pathway resulting from insufficient blood supply to bone, commonly the femoral head. There are many postulated etiologies of non-traumatic AVN, including corticosteroids, bisphosphonates, and radiotherapy (RT). However, it is unclear whether there is a dose threshold for the development of RT-induced AVN. In this case report, we describe a patient with prostate cancer metastatic to bone diagnosed with AVN after receiving single-fraction palliative RT to the left femoral head. Potential contributing factors are discussed, along with a review of other reported cases. At present, the RT dose threshold below which there is no risk for AVN is unknown, and therefore detrimental impact from the RT cannot be excluded. Given the possibility that RT-induced AVN is a stochastic effect, it is important to be aware of the possibility of this diagnosis in any patient with a painful hip who has received RT to the femoral head.

  5. Is it really an abscess? An unusual case of metastatic stromal cell sarcoma of the prostate

    Directory of Open Access Journals (Sweden)

    Shehan Wickramasinghe

    2015-01-01

    Conclusion: The preferred treatment for prostatic stromal cell sarcoma is surgery by radical prostatectomy or cystoprostatectomy. There is currently not enough literature on the topic to elucidate the role of chemo- or radiotherapy in loco-regional or distant spread.

  6. Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial

    NARCIS (Netherlands)

    Basch, E.; Autio, K.; Ryan, C.J.; Mulders, P.; Shore, N.; Kheoh, T.; Fizazi, K.; Logothetis, C.J.; Rathkopf, D.; Smith, M.R.; Mainwaring, P.N.; Hao, Y.; Griffin, T.; Li, S.; Meyers, M.L.; Molina, A.; Cleeland, C.

    2013-01-01

    BACKGROUND: Abiraterone acetate plus prednisone significantly improves radiographic progression-free survival in asymptomatic or mildly symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer compared with prednisone alone. We describe analyses of data for patie

  7. Yes-mediated phosphorylation of focal adhesion kinase at tyrosine 861 increases metastatic potential of prostate cancer cells.

    Science.gov (United States)

    Chatterji, Tanushree; Varkaris, Andreas S; Parikh, Nila U; Song, Jian H; Cheng, Chien-Jui; Schweppe, Rebecca E; Alexander, Stephanie; Davis, John W; Troncoso, Patricia; Friedl, Peter; Kuang, Jian; Lin, Sue-Hwa; Gallick, Gary E

    2015-04-30

    To study the role of FAK signaling complexes in promoting metastatic properties of prostate cancer (PCa) cells, we selected stable, highly migratory variants, termed PC3 Mig-3 and DU145 Mig-3, from two well-characterized PCa cell lines, PC3 and DU145. These variants were not only increased migration and invasion in vitro, but were also more metastatic to lymph nodes following intraprostatic injection into nude mice. Both PC3 Mig-3 and DU145 Mig-3 were specifically increased in phosphorylation of FAK Y861. We therefore examined potential alterations in Src family kinases responsible for FAK phosphorylation and determined only Yes expression was increased. Overexpression of Yes in PC3 parental cells and src-/-fyn-/-yes-/- fibroblasts selectively increased FAK Y861 phosphorylation, and increased migration. Knockdown of Yes in PC3 Mig-3 cells decreased migration and decreased lymph node metastasis following orthotopic implantation of into nude mice. In human specimens, Yes expression was increased in lymph node metastases relative to paired primary tumors from the same patient, and increased pFAK Y861 expression in lymph node metastases correlated with poor prognosis. These results demonstrate a unique role for Yes in phosphorylation of FAK and in promoting PCa metastasis. Therefore, phosphorylated FAK Y861 and increased Yes expression may be predictive markers for PCa metastasis.

  8. RANKL/RANK/MMP-1 molecular triad contributes to the metastatic phenotype of breast and prostate cancer cells in vitro.

    Directory of Open Access Journals (Sweden)

    Sandra Casimiro

    Full Text Available The osteolytic nature of bone metastasis results from a tumor-driven increased bone resorption. Bone remodeling is orchestrated by the molecular triad RANK-RANKL-OPG. This process is dysregulated in bone metastases, mostly via induction of RANKL by tumor-derived factors. These factors increase expression of RANKL, which induce osteoclast formation, function, and survival, thereby increasing bone resorption. RANK is unexpectedly expressed by cancer cells, and the activation of RANKL-RANK pathway correlates with an increased invasive phenotype. To investigate the interaction between RANK expression in human breast and prostate cancer cells and their pro-metastatic phenotype we analyzed the activation of RANKL-RANK pathway and its effects on cell migration, invasion, gene expression in vitro, and osteolysis-inducing ability in vivo. RANKL activates kinase signaling pathways, stimulates cell migration, increases cell invasion, and up-regulates MMP-1 expression. In vivo, MMP-1 knockdown resulted in smaller x-ray osteolytic lesions and osteoclastogenesis, and decreased tumor burden. Therefore, RANKL inhibition in bone metastatic disease may decrease the levels of the osteoclastogenesis inducer MMP-1, contributing to a better clinical outcome.

  9. Sarcosine Up-Regulates Expression of Genes Involved in Cell Cycle Progression of Metastatic Models of Prostate Cancer

    Science.gov (United States)

    Heger, Zbynek; Merlos Rodrigo, Miguel Angel; Michalek, Petr; Polanska, Hana; Masarik, Michal; Vit, Vitezslav; Plevova, Mariana; Pacik, Dalibor; Eckschlager, Tomas; Stiborova, Marie

    2016-01-01

    The effects of sarcosine on the processes driving prostate cancer (PCa) development remain still unclear. Herein, we show that a supplementation of metastatic PCa cells (androgen independent PC-3 and androgen dependent LNCaP) with sarcosine stimulates cells proliferation in vitro. Similar stimulatory effects were observed also in PCa murine xenografts, in which sarcosine treatment induced a tumor growth and significantly reduced weight of treated mice (p < 0.05). Determination of sarcosine metabolism-related amino acids and enzymes within tumor mass revealed significantly increased glycine, serine and sarcosine concentrations after treatment accompanied with the increased amount of sarcosine dehydrogenase. In both tumor types, dimethylglycine and glycine-N-methyltransferase were affected slightly, only. To identify the effects of sarcosine treatment on the expression of genes involved in any aspect of cancer development, we further investigated expression profiles of excised tumors using cDNA electrochemical microarray followed by validation using the semi-quantitative PCR. We found 25 differentially expressed genes in PC-3, 32 in LNCaP tumors and 18 overlapping genes. Bioinformatical processing revealed strong sarcosine-related induction of genes involved particularly in a cell cycle progression. Our exploratory study demonstrates that sarcosine stimulates PCa metastatic cells irrespectively of androgen dependence. Overall, the obtained data provides valuable information towards understanding the role of sarcosine in PCa progression and adds another piece of puzzle into a picture of sarcosine oncometabolic potential. PMID:27824899

  10. A receptor tyrosine kinase, UFO/Axl, and other genes isolated by a modified differential display PCR are overexpressed in metastatic prostatic carcinoma cell line DU145.

    Science.gov (United States)

    Jacob, A N; Kalapurakal, J; Davidson, W R; Kandpal, G; Dunson, N; Prashar, Y; Kandpal, R P

    1999-01-01

    We have used a modified differential display PCR protocol for isolating 3' restriction fragments of cDNAs specifically expressed or overexpressed in metastatic prostate carcinoma cell line DU145. Several cDNA fragments were identified that matched to milk fat globule protein, UFO/Axl, a receptor tyrosine kinase, human homologue of a Xenopus maternal transcript, laminin and laminin receptor, human carcinoma-associated antigen, and some expressed sequence tags. The transcript for milk fat globule protein, a marker protein shown to be overexpressed in breast tumors, was elevated in DU145 cells. The expression of UFO/Axl, a receptor tyrosine kinase, was considerably higher in DU145 cells as compared to normal prostate cells and prostatic carcinoma cell line PC-3. The overexpression of UFO oncogene in DU145 cells is discussed in the context of prostate cancer metastasis.

  11. Tumor phosphatidylinositol-3-kinase signaling and development of metastatic disease in locally advanced rectal cancer.

    Directory of Open Access Journals (Sweden)

    Anne Hansen Ree

    Full Text Available BACKGROUND: Recognizing EGFR as key orchestrator of the metastatic process in colorectal cancer, but also the substantial heterogeneity of responses to anti-EGFR therapy, we examined the pattern of composite tumor kinase activities governed by EGFR-mediated signaling that might be implicated in development of metastatic disease. PATIENTS AND METHODS: Point mutations in KRAS, BRAF, and PIK3CA and ERBB2 amplification were determined in primary tumors from 63 patients with locally advanced rectal cancer scheduled for radical treatment. Using peptide arrays with tyrosine kinase substrates, ex vivo phosphopeptide profiles were generated from the same baseline tumor samples and correlated to metastasis-free survival. RESULTS: Unsupervised clustering analysis of the resulting phosphorylation of 102 array substrates defined two tumor classes, both consisting of cases with and without KRAS/BRAF mutations. The smaller cluster group of patients, with tumors generating high ex vivo phosphorylation of phosphatidylinositol-3-kinase-related substrates, had a particularly aggressive disease course, with almost a half of patients developing metastatic disease within one year of follow-up. CONCLUSION: High phosphatidylinositol-3-kinase-mediated signaling activity of the primary tumor, rather than KRAS/BRAF mutation status, was identified as a hallmark of poor metastasis-free survival in patients with locally advanced rectal cancer undergoing radical treatment of the pelvic cavity.

  12. Radium-223 dichloride: illustrating the benefits of a multidisciplinary approach for patients with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Renzulli II JF

    2015-06-01

    Full Text Available Joseph F Renzulli II, Jennifer Collins, Anthony Mega Genitourinary Multidisciplinary Clinic, The Miriam Hospital, Providence, RI, USAAbstract: Improving options for patients with metastatic castration-resistant prostate cancer (mCRPC provide latitude in designing treatment plans that meet patients' medical needs and personal goals. The field's rapid evolution opens avenues for contributions by multiple medical specialties and requires considering more options to ensure that each patient receives the most appropriate care. A multidisciplinary clinic (MDC focusing on patients with cancers of the genitourinary tract demonstrates an efficient and cost-effective means of integrating the diverse professional knowledge and skills needed to develop an optimal patient treatment plan. As a guide to establishing an MDC for patients with mCRPC, this article describes the operation of the Genitourinary MDC at The Miriam Hospital in Providence, RI – specifically, the successful incorporation of radium-223 dichloride (radium-223 into the treatment algorithm for men with mCRPC and symptomatic bone metastases. Radium-223 is a new treatment that, unlike earlier radionuclide therapies, has shown a survival advantage in a large randomized phase 3 trial (ALSYMPCA. The overall survival benefit was comparable to that of newer immuno- and hormonal therapies in similar populations. Radium-223 treatment also delayed onset of symptomatic skeletal events. Both benefits were independent of prior docetaxel therapy or concurrent bisphosphonate use. In our clinic, radium-223 is used primarily to extend patient survival. Patient selection, patient management, and treatment sequencing are discussed here in the context of a multidisciplinary environment. Keywords: radium-223 dichloride, prostate cancer, castration-resistant prostate cancer, multidisciplinary clinic, best practices

  13. CD57 Expression in Incidental, Clinically Manifest, and Metastatic Carcinoma of the Prostate

    Directory of Open Access Journals (Sweden)

    Holger Wangerin

    2014-01-01

    Full Text Available Objectives. CD57 is normally found on NK-cells, but little is known about its expression in prostatic tissue. Methods. We investigated CD57 expression by immunohistochemistry using tissue microarrays containing 3262 prostate cancers (PCa, lymph node metastases, and benign prostatic tissue. The results were compared with clinical and pathological parameters. Results. Overall, 87% of PCa showed a moderate or strong expression of CD57. There was no significant difference to corresponding benign prostatic tissue. CD57 was increasingly lost from incidental over clinically manifest cancers to metastases. It correlated significantly with Gleason grade and pT-category, but not with PSA tissue expression. Loss of CD57 expression was an independent risk factor for PSA recurrence after prostatectomy in a multivariate Cox regression analysis. In standard sections, CD57 expression was heterogeneous, especially in large, high-grade PCa. Conclusions. There is a peculiar expression of CD57 in PCa and benign prostatic tissue. CD57 loss is associated with tumor dedifferentiation and tumor size. However, the use of this marker for prognostic purposes is hampered by its heterogeneous expression.

  14. Serum testosterone as a prognostic factor in patients with advanced prostatic carcinoma

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Christensen, I J

    1994-01-01

    In 245 patients with previously untreated advanced carcinoma of the prostate, serum concentrations of testosterone have been measured before androgen deprivation therapy, and patients were divided in quartiles according to their serum concentration. Pretreatment level of serum testosterone...... parameters suggest that low serum testosterone merely is a consequence of the advanced malignancy rather than a causative factor in the pathogenesis of prostatic cancer....

  15. Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial

    NARCIS (Netherlands)

    Saad, F.; Fizazi, K.; Jinga, V.; Efstathiou, E.; Fong, P.C.; Hart, L.L.; Jones, R.; McDermott, R.; Wirth, M.; Suzuki, K.; MacLean, D.B.; Wang, L.; Akaza, H.; Nelson, J.; Scher, H.I.; Dreicer, R.; Webb, I.J.; Wit, R. de; Oort, I.M. van

    2015-01-01

    BACKGROUND: Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resist

  16. Sipuleucel-T in patients with metastatic castration-resistant prostate cancer: an insight for oncologists.

    Science.gov (United States)

    Garcia, Jorge A

    2011-03-01

    Sipuleucel-T represents a novel immunotherapeutic compound designed to stimulate an immune response against castration-resistant prostate cancer (CRPC). Sipuleucel-T is an autologous active cellular immunotherapy product, which includes autologous dendritic cells pulsed ex vivo with PAP2024, a recombinant fusion protein made of prostatic acid phosphatase and granulocyte-macrophage colony-stimulating factor. Despite the lack of prostate-specific antigen and objective response, a recent phase III randomized trial demonstrated a significant improvement in overall survival in asymptomatic and minimally symptomatic CRPC patients. This review summarizes the clinical development of Sipuleucel-T in CRPC that led to the regulatory approval of this compound in the USA.

  17. The HIF1A functional genetic polymorphism at locus +1772 associates with progression to metastatic prostate cancer and refractoriness to hormonal castration.

    Science.gov (United States)

    Fraga, Avelino; Ribeiro, Ricardo; Príncipe, Paulo; Lobato, Carlos; Pina, Francisco; Maurício, Joaquina; Monteiro, Cátia; Sousa, Hugo; Calais da Silva, F; Lopes, Carlos; Medeiros, Rui

    2014-01-01

    The hypoxia inducible factor 1 alpha (HIF1a) is a key regulator of tumour cell response to hypoxia, orchestrating mechanisms known to be involved in cancer aggressiveness and metastatic behaviour. In this study we sought to evaluate the association of a functional genetic polymorphism in HIF1A with overall and metastatic prostate cancer (PCa) risk and with response to androgen deprivation therapy (ADT). The HIF1A +1772 C>T (rs11549465) polymorphism was genotyped, using DNA isolated from peripheral blood, in 1490 male subjects (754 with prostate cancer and 736 controls cancer-free) through Real-Time PCR. A nested group of cancer patients who were eligible for androgen deprivation therapy was followed up. Univariate and multivariate models were used to analyse the response to hormonal treatment and the risk for developing distant metastasis. Age-adjusted odds ratios were calculated to evaluate prostate cancer risk. Our results showed that patients under ADT carrying the HIF1A +1772 T-allele have increased risk for developing distant metastasis (OR, 2.0; 95%CI, 1.1-3.9) and an independent 6-fold increased risk for resistance to ADT after multivariate analysis (OR, 6.0; 95%CI, 2.2-16.8). This polymorphism was not associated with increased risk for being diagnosed with prostate cancer (OR, 0.9; 95%CI, 0.7-1.2). The HIF1A +1772 genetic polymorphism predicts a more aggressive prostate cancer behaviour, supporting the involvement of HIF1a in prostate cancer biological progression and ADT resistance. Molecular profiles using hypoxia markers may help predict clinically relevant prostate cancer and response to ADT.

  18. Systemic and Gene Modified Mesenchymal Stem Cell Therapy for Metastatic Prostate Cancer

    Science.gov (United States)

    2009-05-01

    statistics, 2008. CA Cancer J Clin 2008;58:71–96. 2. Dhanasekaran SM, Barrette TR, Ghosh D, Shah R, Varambally S, Kurachi K, Pienta KJ, Rubin MA, Chinnaiyan AM...versus normal prostate epithelial cells. Cancer Res 2004;64:6190– 6199. 40. Araki S, Omori Y, Lyn D, Singh RK, Meinbach DM, Sandman Y, Lokeshwar VB

  19. Orofacial pain and numb chin syndrome as the presenting symptoms of a metastatic prostate cancer.

    Directory of Open Access Journals (Sweden)

    Gaver A

    2002-10-01

    Full Text Available We describe a patient with orofacial pain as the presenting symptom caused by a mandibular metastasis from a previously undiagnosed cancer of the prostate. This possibility should be considered in the differential diagnosis of male patients presenting with orofacial pain.

  20. Low-molecular-weight protein tyrosine phosphatase predicts prostate cancer outcome by increasing the metastatic potential

    NARCIS (Netherlands)

    R.R. Ruela-de-Sousa (Roberta); E. Hoekstra (Elmer); A.M. Hoogland (Marije); K.C. de Souza Queiroz (Karla); M.P. Peppelenbosch (Maikel); A. Stubbs (Andrew); K.J. Pelizzaro-Rocha (Karin); G.J.H.L. Leenders (Geert); G.W. Jenster (Guido); H. Aoyama (Hiroshi); C.V. Ferreira (Carmen); G.M. Fuhler (Gwenny)

    2016-01-01

    textabstractBackground Low-risk patients suffering from prostate cancer (PCa) are currently placed under active surveillance rather than undergoing radical prostatectomy. However, clear parameters for selecting the right patient for each strategy are not available, and new biomarkers and treatment m

  1. Vismodegib: The first drug approved for advanced and metastatic basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    A K Dubey

    2013-01-01

    Full Text Available Treatment of basal cell carcinoma (BCC usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA. The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  2. Vismodegib: the first drug approved for advanced and metastatic basal cell carcinoma.

    Science.gov (United States)

    Dubey, A K; Dubey, S; Handu, S S; Qazi, M A

    2013-01-01

    Treatment of basal cell carcinoma (BCC) usually involves surgical interventions and laser ablation, but in locally advanced BCC, which arise either from earlier untreated lesions or from recurrence of aggressive BCC, surgery and radiotherapy are not helpful. Vismodegib, the first oral-targeted therapy for locally advanced and metastatic BCC, unsuitable for surgery or radiotherapy, was recently approved by US Food and Drug Administration (FDA). The drug was under the priority review program of FDA and was approved on the basis of promising results of phase II trial. Vismodegib acts by targeting the hedgehog pathway, which is activated abnormally in most BCCs. Approval of vismodegib is a big step ahead in the treatment of advanced BCC, where there was no other effective drug therapy till now.

  3. Phase IIa Clinical Trial of Trans-1-Amino-3-18F-Fluoro- Cyclobutane Carboxylic Acid in Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Yusuke Inoue

    2014-10-01

    Full Text Available Objective(s: We performed a phase IIa clinical trial of trans-1-amino-3-18Ffluoro-cyclobutane carboxylic acid (anti-18F-FACBC, a synthetic amino acid analog for PET, in patients with metastatic prostate cancer. Methods: The study subjects consisted of 10 untreated prostate cancer patients having lymph node and/or bone metastasis. Five patients underwent whole-body PET 5 and 30 min after intravenous injection of anti-18F-FACBC. The other five patients underwent 60 min dynamic PET of the pelvis. Safety assessment was performed before and 24 h after injection. PET/CT images were assessed visually, and time courses of anti-18F-FACBC uptake were evaluated from dynamic imaging. Results: Two mild adverse events were observed and resolved without treatment. All 10 patients showed increased accumulation of anti-18F-FACBC in the primary prostate lesion. CT revealed five enlarged lymph nodes indicating metastasis, and all showed increased uptake. Additionally, anti-18F-FACBC PET delineated unenlarged lymph nodes as hot spots. Anti-18F-FACBC PET demonstrated metastatic bone lesions, similar to conventional imaging. In one of two patients with lung metastasis, some lesions showed increased uptake. Regarding the time course, increased uptake of anti-18F-FACBC in the lesion was demonstrated immediately after injection, followed by gradual washout. Conclusion: The results of this phase IIa clinical trial indicated the safety of anti-18F-FACBC in patients with prostate cancer and the potential of anti-18F-FACBC PET to delineate primary prostate lesions and metastatic lesions. This clinical trial was registered as JapicCTI-101326.

  4. Phase IIa Clinical Trial of Trans-1-Amino-3-18F-Fluoro-Cyclobutane Carboxylic Acid in Metastatic Prostate Cancer

    Science.gov (United States)

    Inoue, Yusuke; Asano, Yuji; Satoh, Takefumi; Tabata, Ken-ichi; Kikuchi, Kei; Woodhams, Reiko; Baba, Shiro; Hayakawa, Kazushige

    2014-01-01

    Objective(s): We performed a phase IIa clinical trial of trans-1-amino-3-18F-fluoro-cyclobutane carboxylic acid (anti-18F-FACBC), a synthetic amino acid analog for PET, in patients with metastatic prostate cancer. Methods: The study subjects consisted of 10 untreated prostate cancer patients having lymph node and/or bone metastasis. Five patients underwent whole-body PET 5 and 30 min after intravenous injection of anti-18F-FACBC. The other five patients underwent 60 min dynamic PET of the pelvis. Safety assessment was performed before and 24 h after injection. PET/CT images were assessed visually, and time courses of anti-18F-FACBC uptake were evaluated from dynamic imaging. Results: Two mild adverse events were observed and resolved without treatment. All 10 patients showed increased accumulation of anti-18F-FACBC in the primary prostate lesion. CT revealed five enlarged lymph nodes indicating metastasis, and all showed increased uptake. Additionally, anti-18F-FACBC PET delineated unenlarged lymph nodes as hot spots. Anti-18F-FACBC PET demonstrated metastatic bone lesions, similar to conventional imaging. In one of two patients with lung metastasis, some lesions showed increased uptake. Regarding the time course, increased uptake of anti-18F-FACBC in the lesion was demonstrated immediately after injection, followed by gradual washout. Conclusion: The results of this phase IIa clinical trial indicated the safety of anti-18F-FACBC in patients with prostate cancer and the potential of anti-18F-FACBC PET to delineate primary prostate lesions and metastatic lesions. This clinical trial was registered as JapicCTI-101326. PMID:27408864

  5. Plasma levels of trefoil factors are increased in patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Vestergaard, Else Marie; Borre, Michael; Poulsen, Steen Seier;

    2006-01-01

    . EXPERIMENTAL DESIGN: In 79 patients with prostate cancer, 23 patients with benign prostatic hyperplasia, and 44 healthy individuals plasma TFF1, TFF2, and TFF3 were determined with ELISAs and compared with clinical stage and prostate-specific antigen (PSA) values. Plasma levels of TFF were compared......PURPOSE: Through cDNA array analyses and immunohistochemistry on tissue microarrays, trefoil factor 3 (TFF3) was recently shown to be overexpressed in prostate cancer. The purpose of this study was to test the feasibility of using the levels of trefoil factors as a plasma marker for prostate cancer...... with the immunohistochemical expression of TFF and chromogranin A in 30 prostate cancer tissue samples. RESULTS: Patients with advanced prostate cancer had significantly higher plasma concentrations of TFF1, TFF2, and TFF3 (P

  6. Progression of metastatic castrate-resistant prostate cancer: impact of therapeutic intervention in the post-docetaxel space.

    Science.gov (United States)

    Sartor, A Oliver

    2011-04-23

    Despite the proven success of hormonal therapy for prostate cancer using chemical or surgical castration, most patients eventually will progress to a phase of the disease that is metastatic and shows resistance to further hormonal manipulation. This has been termed metastatic castrate-resistant prostate cancer (mCRPC). Despite this designation, however, there is evidence that androgen receptor (AR)-mediated signaling and gene expression can persist in mCRPC, even in the face of castrate levels of androgen. This may be due in part to the upregulation of enzymes involved in androgen synthesis, the overexpression of AR, or the emergence of mutant ARs with promiscuous recognition of various steroidal ligands. The therapeutic options were limited and palliative in nature until trials in 2004 demonstrated that docetaxel chemotherapy could significantly improve survival. These results established first-line docetaxel as the standard of care for mCRPC. After resistance to further docetaxel therapy develops, treatment options were once again limited. Recently reported results from phase 3 trials have shown that additional therapy with the novel taxane cabazitaxel (with prednisone), or treatment with the antiandrogen abiraterone (with prednisone) could improve survival for patients with mCRPC following docetaxel therapy. Compared with mitoxantrone/prednisone, cabazitaxel/prednisone significantly improved overall survival, with a 30% reduction in rate of death, in patients with progression of mCRPC after docetaxel therapy in the TROPIC trial. Similarly, abiraterone acetate (an inhibitor of androgen biosynthesis) plus prednisone significantly decreased the rate of death by 35% compared with placebo plus prednisone in mCRPC patients progressing after prior docetaxel therapy in the COU-AA-301 trial. Results of these trials have thus established two additional treatment options for mCRPC patients in the "post-docetaxel space." In view of the continued AR-mediated signaling on m

  7. Progression of metastatic castrate-resistant prostate cancer: impact of therapeutic intervention in the post-docetaxel space

    Directory of Open Access Journals (Sweden)

    Sartor A Oliver

    2011-04-01

    Full Text Available Abstract Despite the proven success of hormonal therapy for prostate cancer using chemical or surgical castration, most patients eventually will progress to a phase of the disease that is metastatic and shows resistance to further hormonal manipulation. This has been termed metastatic castrate-resistant prostate cancer (mCRPC. Despite this designation, however, there is evidence that androgen receptor (AR-mediated signaling and gene expression can persist in mCRPC, even in the face of castrate levels of androgen. This may be due in part to the upregulation of enzymes involved in androgen synthesis, the overexpression of AR, or the emergence of mutant ARs with promiscuous recognition of various steroidal ligands. The therapeutic options were limited and palliative in nature until trials in 2004 demonstrated that docetaxel chemotherapy could significantly improve survival. These results established first-line docetaxel as the standard of care for mCRPC. After resistance to further docetaxel therapy develops, treatment options were once again limited. Recently reported results from phase 3 trials have shown that additional therapy with the novel taxane cabazitaxel (with prednisone, or treatment with the antiandrogen abiraterone (with prednisone could improve survival for patients with mCRPC following docetaxel therapy. Compared with mitoxantrone/prednisone, cabazitaxel/prednisone significantly improved overall survival, with a 30% reduction in rate of death, in patients with progression of mCRPC after docetaxel therapy in the TROPIC trial. Similarly, abiraterone acetate (an inhibitor of androgen biosynthesis plus prednisone significantly decreased the rate of death by 35% compared with placebo plus prednisone in mCRPC patients progressing after prior docetaxel therapy in the COU-AA-301 trial. Results of these trials have thus established two additional treatment options for mCRPC patients in the "post-docetaxel space." In view of the continued AR

  8. Glyphosate Vedotin for Treatment of Bone Metastatic Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2015-07-01

    and AR gene mutations [2], may cause hypersensitivity of AR to low levels of both endocrine and intracrine androgens [3]. AR splicing variants may...Medium containing 10% fetal bovine serum (HyClone, Logan, UT, USA) and 100 IU/mL penicillin /streptomycin, in a 5% CO 2 humidified incubator at 37°C...USA) with 10% fetal bovine serum (FBS; Mediatech, Inc.) and 1% penicillin /streptomycin was used as the growth medium. Mouse prostate tissues were

  9. Recombinant Platform for Prioritizing Aerolysin Molecular Grenades for Metastatic Prostate Cancer

    Science.gov (United States)

    2015-10-01

    will use a recombinant molecular biology platform to produce a series of molecular grenades, each based upon the bacterial toxin proaerolysin, but...Engineer enzymatically cleavable linker for the release and activation of PA from HSA with lead peptides. Using standard molecular biology techniques to...mouse models. Other avenues of training enrichment include attending the biannual Prostate Cancer United Kingdom meeting which arranged PCa

  10. Oncogenic LINE-1 Retroelements Sustain Prostate Tumor Cells and Promote Metastatic Progression

    Science.gov (United States)

    2015-10-01

    proved challenging and we are mid- way . For Task 3, we cloned the main variant of PIWIL1, and have it under tetracycline/doxycycline control in a...RNA-sequencing data that we are part way through processing, but suggests so far significant activation of non-coding RNA sequences derived from RNA...its expression in non-tumorigenic prostate cells. Finally, we have cloned the PIWIL-1 gene, known as a repressor of LINE-1 retroelement sequences

  11. Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone.

    Science.gov (United States)

    Sharma, Sambad; Xing, Fei; Liu, Yin; Wu, Kerui; Said, Neveen; Pochampally, Radhika; Shiozawa, Yusuke; Lin, Hui-Kuan; Balaji, K C; Watabe, Kounosuke

    2016-09-09

    Prostate cancer is known to frequently recur in bone; however, how dormant cells switch its phenotype leading to recurrent tumor remains poorly understood. We have isolated two syngeneic cell lines (indolent and aggressive) through in vivo selection by implanting PC3mm stem-like cells into tibial bones. We found that indolent cells retained the dormant phenotype, whereas aggressive cells grew rapidly in bone in vivo, and the growth rates of both cells in culture were similar, suggesting a role of the tumor microenvironment in the regulation of dormancy and recurrence. Indolent cells were found to secrete a high level of secreted protein acidic and rich in cysteine (SPARC), which significantly stimulated the expression of BMP7 in bone marrow stromal cells. The secreted BMP7 then kept cancer cells in a dormant state by inducing senescence, reducing "stemness," and activating dormancy-associated p38 MAPK signaling and p21 expression in cancer cells. Importantly, we found that SPARC was epigenetically silenced in aggressive cells by promoter methylation, but 5-azacytidine treatment reactivated the expression. Furthermore, high SPARC promoter methylation negatively correlated with disease-free survival of prostate cancer patients. We also found that the COX2 inhibitor NS398 down-regulated DNMTs and increased expression of SPARC, which led to tumor growth suppression in bone in vivo These findings suggest that SPARC plays a key role in maintaining the dormancy of prostate cancer cells in the bone microenvironment.

  12. Cost-effectiveness analysis of abiraterone and sipuleucel-T in asymptomatic metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Gong, Cynthia L; Hay, Joel W

    2014-10-01

    Of patients diagnosed with prostate cancer, 0% to 20% experience disease progression to metastatic castration-resistant prostate cancer (mCRPC). Recently, 4 novel therapies have been introduced for the treatment of mCRPC; of these, abiraterone and sipuleucel-T have been studied in the asymptomatic, pre-docetaxel population. Both have shown clinical benefits compared with placebo. This study evaluated the cost-effectiveness of abiraterone acetate and sipuleucel-T compared with prednisone in asymptomatic, pre-docetaxel mCRPC from a US societal perspective. A Markov model was constructed to simulate stable disease, progressed disease, and death. Survival and event rates were derived from published clinical trial data. Costs were derived from the literature and government reimbursement schedules. Outcomes were measured as average cost-effectiveness ratios (ACERs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). One-way and probabilistic sensitivity analyses were conducted to test the robustness of the model. The base-case ACER was $114K/quality-adjusted life-years (QALY) for abiraterone, $85K/QALY for sipuleucel-T, and $31K/QALY for prednisone. The base-case ICER was $389K/QALY for abiraterone and $547K/QALY for sipuleucel-T. Prednisone dominates both abiraterone and sipuleucel-T in terms of NMB at willingness-to-pay (WTP) thresholds of $400K or less. One-way sensitivity analyses revealed that the model was most sensitive to overall survival and utility inputs. Probabilistic sensitivity analyses showed abiraterone to be cost-effective 50% or more of the time at a WTP of greater than $400K, whereas sipuleucel-T was cost-effective 50% or more of the time at a WTP of greater than $270K. Neither abiraterone nor sipuleucel-T was found to be cost-effective compared with prednisone in the treatment of asymptomatic, pre-docetaxel mCRPC.

  13. Hormonal therapy and chemotherapy in patients with hormone-sensitive prostate cancer

    Directory of Open Access Journals (Sweden)

    R. A. Gafanov

    2016-01-01

    Full Text Available Prostate cancer is the most common men`s cancer in men in developed world and the second cause of death in this population. This review focuses on management of advanced castration resistant prostate cancer (CRPC has been rapidly changing and is still evolving. In the last years, there has been an increasing knowledge of prostate cancer biology. New therapeutic agents and approaches have been evaluated demonstrating benefits in survival and quality of life in patients with metastatic prostate cancer.

  14. Targeting Bone Metabolism in Patients with Advanced Prostate Cancer: Current Options and Controversies

    Directory of Open Access Journals (Sweden)

    Tilman Todenhöfer

    2015-01-01

    Full Text Available Maintaining bone health remains a clinical challenge in patients with prostate cancer (PC who are at risk of developing metastatic bone disease and increased bone loss due to hormone ablation therapy. In patients with cancer-treatment induced bone loss (CTIBL, antiresorptive agents have been shown to improve bone mineral density (BMD and to reduce the risk of fractures. For patients with bone metastases, both zoledronic acid and denosumab delay skeletal related events (SREs in the castration resistant stage of disease. Novel agents targeting the Wnt inhibitors dickkopf-1 and sclerostin are currently under investigation for the treatment of osteoporosis and malignant bone disease. New antineoplastic drugs such as abiraterone, enzalutamide, and Radium-223 are capable of further delaying SREs in patients with advanced PC. The benefit of antiresorptive treatment for patients with castration sensitive PC appears to be limited. Recent trials on the use of zoledronic acid for the prevention of bone metastases failed to be successful, whereas denosumab delayed the occurrence of bone metastases by a median of 4.1 months. Currently, the use of antiresorptive drugs to prevent bone metastases still remains a field of controversies and further trials are needed to identify patient subgroups that may profit from early therapy.

  15. The Prevalence and Importance of Epithelial Plasticity in Metastatic Prostate Cancer

    Science.gov (United States)

    2014-10-01

    34Cancer#13,ඩV110.൛" De"Gasperi,"R.,"Rocher,"A."B.,"Sosa,"M."A.,"Wearne,"S."L.," Perez ,"G."M.,"Friedrich,"V."L.,"Jr.,"Hof,"P."R.,"and൜" Elder,"G."A...34 Nieto ,"M."A."(2012)."Metastatic"colonization"requires"the"repression"of"the"epithelialV36" mesenchymal"transition"inducer"Prrx1."Cancer"Cell#22,螕V724

  16. Association of the innate immunity and inflammation pathway with advanced prostate cancer risk.

    Directory of Open Access Journals (Sweden)

    Rémi Kazma

    Full Text Available Prostate cancer is the most frequent and second most lethal cancer in men in the United States. Innate immunity and inflammation may increase the risk of prostate cancer. To determine the role of innate immunity and inflammation in advanced prostate cancer, we investigated the association of 320 single nucleotide polymorphisms, located in 46 genes involved in this pathway, with disease risk using 494 cases with advanced disease and 536 controls from Cleveland, Ohio. Taken together, the whole pathway was associated with advanced prostate cancer risk (P = 0.02. Two sub-pathways (intracellular antiviral molecules and extracellular pattern recognition and four genes in these sub-pathways (TLR1, TLR6, OAS1, and OAS2 were nominally associated with advanced prostate cancer risk and harbor several SNPs nominally associated with advanced prostate cancer risk. Our results suggest that the innate immunity and inflammation pathway may play a modest role in the etiology of advanced prostate cancer through multiple small effects.

  17. Association of the innate immunity and inflammation pathway with advanced prostate cancer risk.

    Science.gov (United States)

    Kazma, Rémi; Mefford, Joel A; Cheng, Iona; Plummer, Sarah J; Levin, Albert M; Rybicki, Benjamin A; Casey, Graham; Witte, John S

    2012-01-01

    Prostate cancer is the most frequent and second most lethal cancer in men in the United States. Innate immunity and inflammation may increase the risk of prostate cancer. To determine the role of innate immunity and inflammation in advanced prostate cancer, we investigated the association of 320 single nucleotide polymorphisms, located in 46 genes involved in this pathway, with disease risk using 494 cases with advanced disease and 536 controls from Cleveland, Ohio. Taken together, the whole pathway was associated with advanced prostate cancer risk (P = 0.02). Two sub-pathways (intracellular antiviral molecules and extracellular pattern recognition) and four genes in these sub-pathways (TLR1, TLR6, OAS1, and OAS2) were nominally associated with advanced prostate cancer risk and harbor several SNPs nominally associated with advanced prostate cancer risk. Our results suggest that the innate immunity and inflammation pathway may play a modest role in the etiology of advanced prostate cancer through multiple small effects.

  18. Gray level entropy matrix is a superior predictor than multiplex ELISA in the detection of reactive stroma and metastatic potential of high-grade prostatic adenocarcinoma.

    Science.gov (United States)

    Jia, Xiaopeng; Sun, Yanan; Wang, Baozhi

    2014-12-01

    Recent reports have indicated that not only the primary glandular tissue but also the surrounding stromal tissue plays an active role in the progression of carcinoma. Such is true for cancer tissues arising in the prostate. However, the precise role of stromal tissue in benign prostatic hyperplasia (BPH) and prostate adenocarcinoma is not well described. We undertook this current investigation to examine the changes in orientation of the extracellular matrix and correlate with prostatic cancer progression. We used a novel form of image analysis called gray level entropy matrix (GLEM) texture analysis to evaluate morphometric changes in stromal tissues. We used normal prostatic tissue obtained from cadaveric specimen and compared with BPH, prostatic intraepithelium neoplastic, hormone responsive prostatic adenocarcinoma and castration-resistant prostatic adenocarcinoma tissues. GLEM showed higher entropy in disease-resistant prostatic tissues, compared with benign forms of all spectra of pathologically diagnosed prostatic tissues (P entropy is reflective of the disorganized morphological organization of the stroma, possibly reflecting the reactive matrix. In contrast, ELISA revealed that although individually correlated with the progressive stages of benign and carcinomatous prostatic tissues and trend correlation between groups, intergroup comparisons failed to arrive at statistical significance of comparisons between markers of neovasculogenesis, vascular endothelial growth factor, epithelial-mesenchymal transition (beta1-integrin, E-cadherin, MMP3) and osteogenic metastasis (RANKL and osteoprotegerin). The results of our study demonstrate the potential of GLEM entropy of gray level pixel in providing quasiquantitative estimate of a reactive stroma in advance stages of prostatic adenocarcinoma and thus can be routinely used in clinical decision making.

  19. New drugs in the treatment of elderly patients with metastatic castration-resistance prostate cancer.

    Science.gov (United States)

    Genestreti, Giovenzio; Di Battista, Monica; Cavallo, Giovanna; Brandes, Alba A

    2016-08-03

    Treatment of prostate cancer is continually evolving and new therapies have become available. However, the management of elderly patients is challenging due to their age and comorbidities. Androgen deprivation therapy remains the mainstay treatment of hormonal-sensitive disease. Nevertheless, when disease becomes resistant to castration, docetaxel-based chemotherapy represents the standard rescue therapy irrespective of patient age. Recently, chemotherapeutic agents such as cabazitaxel and hormonal therapies such as abiraterone acetate and enzalutamide have been shown to improve survival in patients with progression of disease before or following docetaxel. This review focuses on the safety and efficacy results of these new drugs in elderly patients.

  20. The preclinical development of novel treatment options for advanced prostate cancer

    NARCIS (Netherlands)

    Kroon, Jan

    2016-01-01

    Prostate cancer is a major societal problem with 11.000 new cases every year in the Netherlands. The advanced stage of the disease, castration-resistant prostate cancer, is especially deadly and is often accompanied with (bone) metastases. In this PhD-thesis, we have explored several strategies to i

  1. Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Thomsen, Frederik B; Brasso, Klaus; Christensen, Ib J

    2015-01-01

    -metastatic PCa. Kaplan-Meier analysis was used to estimate overall survival (OS) and multivariate Cox proportional hazard model was performed to analyse time-to-event (death). FINDINGS: A total of 1218 patients were included into the Scandinavian Prostate Cancer Group (SPCG)-6 study of which 607 were randomised......BACKGROUND: The optimal timing of endocrine therapy in non-metastatic prostate cancer (PCa) is still an issue of debate. METHODS: A randomised, double-blind, parallel-group trial comparing bicalutamide 150mg once daily with placebo in addition to standard care in patients with hormone-naïve, non...... disease (HR=1.19 (95% CI: 1.00-1.43), p=0.056). However, a survival gain from bicalutamide therapy was present in patients with localised disease and a baseline PSA greater than 28ng/mL at randomisation. In multivariate Cox proportional hazard model, only including patients managed on watchful waiting...

  2. Tumor-associated Endo180 requires stromal-derived LOX to promote metastatic prostate cancer cell migration on human ECM surfaces.

    Science.gov (United States)

    Caley, Matthew P; King, Helen; Shah, Neel; Wang, Kai; Rodriguez-Teja, Mercedes; Gronau, Julian H; Waxman, Jonathan; Sturge, Justin

    2016-02-01

    The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX). Human osteoblast-derived and fibroblast-derived ECM supported a rounded 'amoeboid-like' mode of cell migration and enhanced Endo180 expression in three prostate cancer cell lines (PC3, VCaP, DU145). Genetic silencing of Endo180 reverted PC3 cells from their rounded mode of migration towards a bipolar 'mesenchymal-like' mode of migration and blocked their translocation on human fibroblast-derived and osteoblast-derived matrices. The concomitant decrease in PC3 cell migration and increase in Endo180 expression induced by stromal LOX inhibition indicates that the Endo180-dependent rounded mode of prostate cancer cell migration requires ECM crosslinking. In conclusion, this study introduces a realistic in vitro model for the study of metastatic prostate cancer cell plasticity and pinpoints the cooperation between tumor-associated Endo180 and the stiff microenvironment imposed by stromal-derived LOX as a potential target for limiting metastatic progression in prostate cancer.

  3. Organoid cultures derived from patients with advanced prostate cancer

    NARCIS (Netherlands)

    Gao, Dong; Vela, Ian; Sboner, Andrea; Iaquinta, Phillip J; Karthaus, Wouter R; Gopalan, Anuradha; Dowling, Catherine; Wanjala, Jackline N; Undvall, Eva A; Arora, Vivek K; Wongvipat, John; Kossai, Myriam; Ramazanoglu, Sinan; Barboza, Luendreo P; Di, Wei; Cao, Zhen; Zhang, Qi Fan; Sirota, Inna; Ran, Leili; MacDonald, Theresa Y; Beltran, Himisha; Mosquera, Juan-Miguel; Touijer, Karim A; Scardino, Peter T; Laudone, Vincent P; Curtis, Kristen R; Rathkopf, Dana E; Morris, Michael J; Danila, Daniel C; Slovin, Susan F; Solomon, Stephen B; Eastham, James A; Chi, Ping; Carver, Brett; Rubin, Mark A; Scher, Howard I; Clevers, Hans; Sawyers, Charles L; Chen, Yu

    2014-01-01

    The lack of in vitro prostate cancer models that recapitulate the diversity of human prostate cancer has hampered progress in understanding disease pathogenesis and therapy response. Using a 3D organoid system, we report success in long-term culture of prostate cancer from biopsy specimens and circu

  4. What is appropriate neoadjuvant/adjuvant androgen deprivation for high-risk/locally advanced prostate cancer?

    Institute of Scientific and Technical Information of China (English)

    Mikio Namiki; Hiroyuki Konaka

    2011-01-01

    @@ The majority of low-risk patients with clinically localized prostate cancer have a high likelihood of disease-free survival,regardless of the treatment option chosen.1 In contrast, patients with high-risk prostate cancer with high Gleason score, elevated prostate-specific antigen level and advanced clinical stage have a high probability of treatment failure after initial management by single-treatment modalities, such as radical pro-statectomy (RP), external beam radiation therapy (EBRT) or brachytherapy.2,3 Therefore, it is extremely important to establish the most effective treatment strategy for patients with high-risk prostate cancer.

  5. Sipuleucel-T (Provenge): active cellular immunotherapy for advanced prostate cancer.

    Science.gov (United States)

    McKarney, I

    2007-09-01

    (1) Sipuleucel-T (Provenge) is an active cellular immunotherapy (therapeutic vaccine) that is designed to stimulate the patient's T-cells to recognize and attack prostate cancer cells that express prostatic acid phosphatase (PAP) antigen. (2) Sipuleucel-T demonstrated a survival benefit in men with advanced androgen-independent prostate cancer (AIPC), although this preliminary finding requires confirmation in larger trials. (3) Mild to moderate myalgia, chills, fever, and tremor are the most commonly reported adverse events for patients receiving sipuleucel-T. These events generally resolve quickly. (4) More studies are needed to evaluate sipuleucel-T in the earlier stages of prostate cancer and in combination with conventional therapies.

  6. Prostatitis

    OpenAIRE

    Domingue, Gerald J.; Hellstrom, Wayne J.G.

    1998-01-01

    The laboratory diagnosis of acute bacterial prostatitis is straightforward and easily accomplished in clinical laboratories. Chronic bacterial prostatitis, and especially chronic idiopathic prostatitis (most often referred to as abacterial prostatitis), presents a real challenge to the clinician and clinical microbiologist. Clinically, the diagnosis of chronic idiopathic prostatitis is differentiated from that of acute prostatitis by a lack of prostatic inflammation and no “significant” (cont...

  7. Unusual presentations of metastatic prostate carcinoma as detected by anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F] FACBC) PET-CT

    Science.gov (United States)

    Amzat, Rianot; Taleghani, Pooneh; Savir-Baruch, Bital; Nieh, Peter T.; Master, Viraj A.; Halkar, Raghuveer K.; Lewis, Melinda M.; Faurot, Michelle; Bellamy, Leah M.; Goodman, Mark M.; Schuster, David M.

    2013-01-01

    Prostate carcinoma is the second most common cause of cancer related mortality in males in the United States. The pattern of metastatic disease of prostate cancer is well recognized, frequently involving sclerotic bone lesions and abdomino-pelvic lymph nodes. Anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid (anti-3-[18F] FACBC) is a synthetic amino acid analog positron emission tomography (PET) radiotracer with reported utility in the detection of prostate carcinoma. We present two cases of unusual presentations of prostate carcinoma, one with malignant ascitis and omental implants and the other with lytic bone lesions detected with anti-3-[18F]FACBC. PMID:21825855

  8. {sup 18}F-Fluorocholine PET/CT for early response assessment in patients with metastatic castration-resistant prostate cancer treated with enzalutamide

    Energy Technology Data Exchange (ETDEWEB)

    De Giorgi, Ugo; Conteduca, Vincenza; Burgio, Salvatore Luca; Menna, Cecilia; Rossi, Lorena; Amadori, Dino [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Department of Medical Oncology, Meldola (Italy); Caroli, Paola; Paganelli, Giovanni; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Diagnostic Nuclear Medicine Unit, Meldola (Italy); Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Moretti, Andrea; Galassi, Riccardo [Morgagni-Pierantoni Hospital, Nuclear Medicine Unit, Forli (Italy)

    2015-07-15

    We investigated the role of {sup 18}F-methylcholine (FCH) PET/CT in the early evaluation of patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide. The study group comprised 36 patients with a median age of 72 years (range 48-90 years) who were treated with enzalutamide 160 mg once daily after at least one chemotherapeutic regimen with docetaxel. Patients were evaluated monthly for serological prostate-specific antigen (PSA) response. FCH PET/CT was performed at baseline and repeated after 3-6 weeks. Univariate and multivariate Cox regression models addressed potential predictors of progression-free survival (PFS) and overall survival (OS). At a median follow-up of 24.2 months (range 1.8-27.3 months), 34 patients were evaluable for early FCH PET/CT evaluation of response, and of these 17 showed progressive disease (PD) and 17 had stable disease or a partial response. A decrease in PSA level of more than 50 % was observed in 21 patients. Early FCH PET/CT PD predicted radiological PD 3 months in advance of CT in 12 of 18 patients (66 %) and was discordant with the decrease in PSA level in 13 patients. In 6 of these, biochemical PD was confirmed in 2 months. In multivariate analysis, only decrease in PSA level and FCH PET/CT were significant predictors of PFS (p = 0.0005 and p = 0.029, respectively), whereas decrease in PSA level alone was predictive of OS (p = 0.007). This is one of the first studies to evaluate the role of FCH PET/CT as an early predictor of outcome in mCRPC patients treated with enzalutamide. Our preliminary results suggest that the combination of FCH PET/CT and decrease in PSA level could be a valid tool to predict PFS in mCRPC patients. PSA remains the single most important prognostic factor, while FCH PET/CT does not add more information on OS beyond that obtained from PSA. Further studies in larger populations are needed to confirm these data and to clarify the role of FCH PET/CT in predicting response

  9. Advancing Treatment for Metastatic Bone Cancer: Consensus Recommendations from the Second Cambridge Conference

    Science.gov (United States)

    Coleman, Robert E.; Guise, Theresa A.; Lipton, Allan; Roodman, G. David; Berenson, James R.; Body, Jean-Jacques; Boyce, Brendan F.; Calvi, Laura M.; Hadji, Peyman; McCloskey, Eugene V.; Saad, Fred; Smith, Matthew R.; Suva, Larry J.; Taichman, Russell S.; Vessella, Robert L.; Weilbaecher, Katherine N.

    2009-01-01

    Purpose Summarize current knowledge, critical gaps in knowledge, and recommendations to advance the field of metastatic bone cancer. Experimental Design A multidisciplinary consensus conference was convened to review recent progress in basic and clinical research, assess critical gaps in current knowledge, and prioritize recommendations to advance research in the next 5 years. The program addressed three principal topics: biology of metastasis, preserving normal bone health, and optimizing bone-targeted therapies. Results A variety of specific recommendations were identified as important to advance research and clinical care over the next 5 years. Conclusions Priorities for research in bone biology include characterizing components of the stem cell niche in bone, developing oncogenic immunocompetent animal models of bone metastasis, and investigating the unique contribution of the bone microenvironment to tumor growth and dormancy. Priorities for research in preserving normal bone health include developing methods to measure and characterize disseminating tumor cells, assessing outcomes from the major prevention trials currently in progress, and improving methodologies to assess risks and benefits of treatment. Priorities for optimizing bone-targeted therapies include advancing studies of serum proteomics and genomics to reliably identify patients who will develop bone metastases, enhancing imaging for early detection of bone metastases and early response evaluation, and developing new tests to evaluate response to bone-directed treatments. PMID:18927277

  10. Facial nerve palsy as a primary presentation of advanced carcinoma of the prostate: An unusual occurrence

    Directory of Open Access Journals (Sweden)

    A. Abdulkadir

    2017-03-01

    Conclusion: Facial nerve palsy as a primary presentation of advanced cancer of the prostate is unusual, thus, a high index of suspicion is required to establish the diagnosis. ADT provided adequate palliation.

  11. [{sup 11}C]Choline positron emission tomography/computed tomography for staging and restaging of patients with advanced prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tuncel, Murat; Souvatzoglou, Michael; Herrmann, Ken [Department of Nuclear Medicine, Klinikum rechts der lsar, Technische Universitaet Muenchen, 81675 Munich (Germany); Stollfuss, Jens [Department of Radiology, Technische Universitaet Muenchen, 81675 Munich (Germany); Schuster, Tibor [Department of Statistics, Technische Universitaet Muenchen, 81675 Munich (Germany); Weirich, Gregor [Department of Pathology, Technische Universitaet Muenchen, 81675 Munich (Germany); Wester, Hans-Juergen; Schwaiger, Markus [Department of Nuclear Medicine, Klinikum rechts der lsar, Technische Universitaet Muenchen, 81675 Munich (Germany); Krause, Bernd J. [Department of Nuclear Medicine, Klinikum rechts der lsar, Technische Universitaet Muenchen, 81675 Munich (Germany)], E-mail: bernd-joachim.krause@tum.de

    2008-08-15

    Introduction: To evaluate [{sup 11}C]Choline positron emission tomography (PET)/computed tomography (CT) for staging and restaging of patients with advanced prostate cancer and to compare the diagnostic performance of PET, CT and PET/CT. Methods: Forty-five consecutive patients with advanced prostate cancer underwent [{sup 11}C]Choline-PET/CT between 5/2004 and 2/2006. Results: Overall, 295 lesions were detected: PET alone, 178 lesions; diagnostic CT, 221 lesions; PET/CT (low-dose CT), 272 lesions; PET/CT (diagnostic CT), 295 lesions. Two thirds of the lesions were located in the bone; one third in the prostate, lymph nodes, periprostatic tissue and soft tissue (lung, liver). The use of diagnostic CT did not result in a statistically significant difference with respect to lesion localization certainty and lesion characterization (P=.063, P=.063). PET-negative but PET/CT-positive lesions were mostly localized in the bone (78%, 91/117) as were PET-positive and CT-negative lesions (72%, 53/74). Of the latter, 91% (48/53) represented bone marrow and 9% (5/53) cortical involvement. Conclusions: Staging and restaging with [{sup 11}C]Choline PET/CT in patients with advanced prostate cancer improve the assessment of local and regional recurrent as well as metastatic disease including skeletal manifestations. [{sup 11}C]Choline PET/CT (with a low-dose CT) results in improved localization and lesion characterization. [{sup 11}C]Choline PET/CT provides an added value for skeletal manifestations. [{sup 11}C]Choline PET/CT changed disease management in 11 (24%) of 45 patients with advanced prostate cancer.

  12. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma.

    Science.gov (United States)

    Lee, Su-Min; Joshi, Jay; Wolfe, Konrad; Acher, Peter; Liyanage, Sidath H

    2016-06-01

    We present a case of nonspecific granulomatous prostatitis (GP), a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

  13. Radiologic presentation of chronic granulomatous prostatitis mimicking locally advanced prostate adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Su-Min Lee

    2016-06-01

    Full Text Available We present a case of nonspecific granulomatous prostatitis (GP, a clinical mimic of prostate adenocarcinoma. A 54-year-old man presented with lower urinary tract symptoms and raised prostate-specific antigen. Magnetic resonance imaging showed features consistent with prostate cancer, including low T2-signal intensity in the peripheral and transition zones with signs of extracapsular extension. Diffusion-weighted imaging showed high-signal intensity, with low apparent diffusion coefficient values, whereas dynamic contrast enhancement demonstrated a type 3 washout curve, similar to that found in prostate cancer. Transperineal sector-guided prostate biopsy confirmed nonspecific GP, and the patient was treated conservatively. We discuss and compare nonspecific, chronic GP as a radiologic mimic of prostate adenocarcinoma patient.

  14. ICON 2013: Practical consensus recommendations for hormone receptor-positive Her2-negative advanced or metastatic breastcancer

    Directory of Open Access Journals (Sweden)

    P M Parikh

    2014-01-01

    Full Text Available The management of hormone receptor-positive Her2-negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

  15. ICON 2013: practical consensus recommendations for hormone receptor-positive Her2-negative advanced or metastatic breastcancer.

    Science.gov (United States)

    Parikh, P M; Gupta, S; Dawood, S; Rugo, H; Bhattacharyya, G S; Agarwal, A; Chacko, R; Sahoo, T P; Babu, G; Agarwal, S; Munshi, A; Goswami, C; Smruti, B K; Bondarde, S; Desai, C; Rajappa, S; Somani, N; Singh, M; Nimmagadda, R; Pavitran, K; Mehta, A; Parmar, V; Desai, S; Nair, R; Doval, D

    2014-01-01

    The management of hormone receptor-positive Her2-negative breast cancer patients with advanced or metastatic disease is a common problem in India and other countries in this region. This expert group used data from published literature, practical experience, and opinion of a large group of academic oncologists, to arrive at practical consensus recommendations for use by the community oncologists.

  16. The prognostic factors of effective ketoconazole treatment for metastatic castration-resistant prostate cancer: who can benefit from ketoconazole therapy?

    Institute of Scientific and Technical Information of China (English)

    Guo-Wen Lin; Xu-Dong Yao; Ding-Wei Ye; Yao Zhu; Shi-Lin Zhang; Bo Dai; Hai-Liang Zhang; Yi-Jun Shen; Chun-Guang Ma

    2012-01-01

    We investigated the prognostic value of some variables of effective ketoconazole treatment for metastatic castration-resistant prostate cancer (mCRPC).In total,163 patients with mCRPC were eligible,receiving ketoconazole 200-400 mg three times daily with replacement doses of prednisone.Progression-free survival (PFS) was calculated from the beginning of the ketoconazole therapy to the onset of disease progression.The prognostic value of different variables for PFS was assessed by Cox regression analysis.The median PFS was 2.6 months (0.5-8.6 months) for these patients.The serum testosterone level changed during therapy,which decreased when the prostate-specific antigen (PSA) declined; the serum testosterone level increased as the levels of PSA relapsed.The median PFS values for patients associated with different factors were the following:1.4 and 3.5 months for a nadir PSA of ≥ 0.2 and <0.2 ng ml-1,respectively (hazard rate (HR)=4.767,P<0.001); 3.1 and 1.6 months for a baseline testosterone of ≥-0.1 and <0.1 ng ml-1,respectively (HR=2.865,P=0.012); 2.8 and 1.9 months for a baseline haemoglobin of ≥ 120 and < 120 gl-1,respectively (HR=1.605,P<0.001); and 3.0 and 1.9 months for a PSA doubling time (PSADT) of ≥ 2.0 and <2.0 months,respectively (HR=1.454,P=0.017).A risk model was constructed according to the four factors that divided patients into three subgroups of low risk (0-1 factors),moderate risk (2 factors) and high risk (3-4 factors) with PFS values of 3.6,3.0 and 1∶4 months,respectively (HR=1.619,P<0.001).A nadir PSA of ≥ 0.2 ng ml-1,a baseline testosterone of <0.1 ng ml-1,a baseline haemoglobin of < 120 gl-1 and a PSADT of <2 months were associated with a poor PFS.This risk model could provide evidence to predict the survival benefit of ketoconazole therapy.

  17. The PREVAIL Study: Primary Outcomes by Site and Extent of Baseline Disease for Enzalutamide-treated Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Evans, Christopher P; Higano, Celestia S; Keane, Thomas;

    2016-01-01

    in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. PATIENT SUMMARY: Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease......BACKGROUND: Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer. OBJECTIVE: To assess...... the effects of enzalutamide versus placebo in patients from PREVAIL based on site and extent of baseline disease. DESIGN, SETTING, AND PARTICIPANTS: One thousand seven hundred and seventeen asymptomatic or minimally symptomatic patients were randomized to enzalutamide (n=872) or placebo (n=845). Subgroup...

  18. Effects of Surgery and Chemotherapy on Metastatic Progression of Prostate Cancer: Evidence from the Natural History of the Disease Reconstructed through Mathematical Modeling

    Directory of Open Access Journals (Sweden)

    Leonid Hanin

    2011-09-01

    Full Text Available This article brings mathematical modeling to bear on the reconstruction of the natural history of prostate cancer and assessment of the effects of treatment on metastatic progression. We present a comprehensive, entirely mechanistic mathematical model of cancer progression accounting for primary tumor latency, shedding of metastases, their dormancy and growth at secondary sites. Parameters of the model were estimated from the following data collected from 12 prostate cancer patients: (1 age and volume of the primary tumor at presentation; and (2 volumes of detectable bone metastases surveyed at a later time. This allowed us to estimate, for each patient, the age at cancer onset and inception of the first metastasis, the expected metastasis latency time and the rates of growth of the primary tumor and metastases before and after the start of treatment. We found that for all patients: (1 inception of the first metastasis occurred when the primary tumor was undetectable; (2 inception of all or most of the surveyed metastases occurred before the start of treatment; (3 the rate of metastasis shedding is essentially constant in time regardless of the size of the primary tumor and so it is only marginally affected by treatment; and most importantly, (4 surgery, chemotherapy and possibly radiation bring about a dramatic increase (by dozens or hundred times for most patients in the average rate of growth of metastases. Our analysis supports the notion of metastasis dormancy and the existence of prostate cancer stem cells. The model is applicable to all metastatic solid cancers, and our conclusions agree well with the results of a similar analysis based on a simpler model applied to a case of metastatic breast cancer.

  19. Effects of Surgery and Chemotherapy on Metastatic Progression of Prostate Cancer: Evidence from the Natural History of the Disease Reconstructed through Mathematical Modeling.

    Science.gov (United States)

    Hanin, Leonid; Zaider, Marco

    2011-09-20

    This article brings mathematical modeling to bear on the reconstruction of the natural history of prostate cancer and assessment of the effects of treatment on metastatic progression. We present a comprehensive, entirely mechanistic mathematical model of cancer progression accounting for primary tumor latency, shedding of metastases, their dormancy and growth at secondary sites. Parameters of the model were estimated from the following data collected from 12 prostate cancer patients: (1) age and volume of the primary tumor at presentation; and (2) volumes of detectable bone metastases surveyed at a later time. This allowed us to estimate, for each patient, the age at cancer onset and inception of the first metastasis, the expected metastasis latency time and the rates of growth of the primary tumor and metastases before and after the start of treatment. We found that for all patients: (1) inception of the first metastasis occurred when the primary tumor was undetectable; (2) inception of all or most of the surveyed metastases occurred before the start of treatment; (3) the rate of metastasis shedding is essentially constant in time regardless of the size of the primary tumor and so it is only marginally affected by treatment; and most importantly, (4) surgery, chemotherapy and possibly radiation bring about a dramatic increase (by dozens or hundred times for most patients) in the average rate of growth of metastases. Our analysis supports the notion of metastasis dormancy and the existence of prostate cancer stem cells. The model is applicable to all metastatic solid cancers, and our conclusions agree well with the results of a similar analysis based on a simpler model applied to a case of metastatic breast cancer.

  20. Food effects on abiraterone pharmacokinetics in healthy subjects and patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Chi, Kim N; Spratlin, Jennifer; Kollmannsberger, Christian; North, Scott; Pankras, Catherine; Gonzalez, Martha; Bernard, Apexa; Stieltjes, Hans; Peng, Lixian; Jiao, James; Acharya, Milin; Kheoh, Thian; Griffin, Thomas W; Yu, Margaret K; Chien, Caly; Tran, Nam Phuong

    2015-12-01

    Food effect on abiraterone pharmacokinetics and safety on abiraterone acetate coadministration with low-fat or high-fat meals was examined in healthy subjects and metastatic castration-resistant prostate cancer (mCRPC) patients. Healthy subjects (n = 36) were randomized to abiraterone acetate (single dose, 1000 mg) + low-fat meal, + high-fat meal, and fasted state. mCRPC patients received repeated doses (abiraterone acetate 1000 mg + 5 mg prednisone twice daily; days 1-7) in a modified fasting state followed by abiraterone acetate plus prednisone within 0.5 hours post-low-fat (n = 6) or high-fat meal (n = 18; days 8-14). In healthy subjects, geometric mean (GM) abiraterone area under plasma concentration-time curve (AUC) increased ∼5- and ∼10-fold, respectively, with low-fat and high-fat meals versus fasted state (GM [coefficient of variation], 1942 [48] and 4077 [37] ng · h/mL vs 421 [67] ng · h/mL, respectively). In mCRPC patients, abiraterone AUC was ∼2-fold higher with a high-fat meal and similar with a low-fat meal versus modified fasting state (GM [coefficient of variation]: 1992 [34] vs 973 [58] ng · h/mL and 1264 [65] vs 1185 [90] ng · h/mL, respectively). Adverse events (all grade ≤ 3) were similar, with high-fat/low-fat meals or fasted/modified fasting state. Short-term dosing with food did not alter abiraterone acetate safety.

  1. Risk factors for metastatic castration-resistant prostate cancer (CRPC predict long-term treatment with docetaxel.

    Directory of Open Access Journals (Sweden)

    Takashi Kawahara

    Full Text Available PURPOSE: For patients with metastatic castration-resistant prostatic cancer (mCRPC, docetaxel plus prednisone leads to superior survival and a higher response rate compared with mitoxantrone plus prednisone. We analyzed the efficacy of long-term treatment with ≥10 cycles of docetaxel, and validated the risk group classification in predicting overall survival (OS in Japanese patients with mCRPC. PATIENTS AND METHODS: Fifty-two patients with mCRPC were administered 55 mg/m(2 docetaxel and 8 mg dexamethasone, every 3 or 4 weeks, simultaneously with hormonal therapy and daily oral dexamethasone. They were divided into two groups, short-term (9 or fewer cycles and long-term (10 or more cycles. Four risk factors including the presence of anemia, bone metastases, significant pain and visceral metastases were utilized for the risk group classification. RESULTS: Fourteen patients (27% had an elevation of PSA in spite of docetaxel treatment, while 23 patients (44% had a decline in PSA level, including 9 patients (17% whose PSA level declined by ≥50%. The median duration of OS after the initiation of this therapy was 11.2 months in the short-term group and 28.5 months in the long-term group. The good risk group showed a significant difference in OS compared with the intermediate and poor risk groups (P<0.001. The median number of cycles of treatment was 14, 4 and 3 for each risk group, respectively (p<0.01. CONCLUSIONS: The present study indicated that ≥10 cycles of this docetaxel therapy can significantly prolong survival in Japanese men with CRPC. This risk group classification for men with mCRPC at the initiation of this chemotherapy is useful.

  2. Therapeutic options in docetaxel-refractory metastatic castration-resistant prostate cancer: a cost-effectiveness analysis.

    Directory of Open Access Journals (Sweden)

    Lixian Zhong

    Full Text Available BACKGROUND: Docetaxel is an established first-line therapy to treat metastatic castration-resistant prostate cancer (mCRPC. Recently, abiraterone and cabazitaxel were approved for use after docetaxel failure, with improved survival. National Institute for Health and Clinical Excellence (NICE preliminary recommendations were negative for both abiraterone (now positive in final recommendation and cabazitaxel (negative in final recommendation. OBJECTIVE: To evaluate the cost-effectiveness of abiraterone, cabazitaxel, mitoxantrone and prednisone for mCRPC treatment in US. METHODS: A decision-tree model was constructed to compare the two mCRPC treatments versus two placebos over 18 months from a societal perspective. Chance nodes include baseline pain as a severity indicator, grade III/IV side-effects, and survival at 18 months. Probabilities, survival and health utilities were from published studies. Model cost inputs included drug treatment, side-effect management and prevention, radiation for pain, and death associated costs in 2010 US dollars. RESULTS: Abiraterone is a cost-effective choice at $94K/QALY (quality adjusted life years compared to placebo in our base-case analysis. Cabazitaxel and abiraterone are the most effective, yet also most expensive agents. The incremental cost-effectiveness ratios (ICER at base-case are $101K/QALY (extended dominated for mitoxantrone vs. placebo, $91K/QALY for abiraterone vs. mitoxantrone, $956K/QALY for cabazitaxel vs. abiraterone. Abiraterone becomes less cost-effective as its AWP increases, or if the cost of mitoxantrone side-effect management decreases. Increases in the percentage of patients with baseline pain leads to an increased ICER for both mitoxantrone and abiraterone, but mitoxantrone does relatively better. Cabazitaxel remains not cost-effective. CONCLUSION: Our base case model suggests that abiraterone is a cost-effective option in docetaxel-refractory mCRPC patients. Newer treatments will also

  3. An elevated serum miR-141 level in patients with bone-metastatic prostate cancer is correlated with more bone lesions

    Institute of Scientific and Technical Information of China (English)

    Hai-Liang Zhang; Xiao-Jian Qin; Da-Long Cao; Yao Zhu; Xu-Dong Yao; Shi-Lin Zhang; Bo Dai

    2013-01-01

    The skeleton is the most common metastatic organ in patients with prostate cancer (PCa).Non-invasive biomarkers that can facilitate the detection and monitoring of bone metastases are highly desirable.We designed this study to assess the expression patterns of serum miR-141 in patients with bone-metastatic PCa.Serum samples were collected to measure the miR-141 level in 56 patients,including six with benign prostatic hyperplasia (BPH),20 with localized PCa and 30 with bone-metastatic PCa (10 with hormone-naive PCa,10 with hormone-sensitive PCa and 10 with hormone-refractory PCa).A bone scan was performed for each patient with PCa to assess the number of bone lesions.The quantification of serum miR-141 levels was assayed by specific TaqMan qRT-PCR.The results showed that serum miR-141 levels were elevated in patients with bone metastasis (P<0.001).There was no statistically significant difference in the serum miR-141 levels between patients with BPH and patients with localized PCa.Using Kendall's bivariate correlation test,both the Gleason score and the number of bone-metastatic lesions were found to correlate with serum miR-141 levels (P=0.012 and P<0.001,respectively).The serum miR-141 level was found to be positively correlated with alkaline phosphatase (ALP) level in patients with skeletal metastasis,using Pearson's bivariate correlation test.No relationship was found between the serum miR-141 level and the serum prostate-specific antigen (PSA) level.We concluded that serum miR-141 levels are elevated in patients with bone-metastatic PCa and that patients with higher levels of serum miR-141 developed more bone lesions.Furthermore,serum miR-141 levels are correlated with serum ALP levels but not serum PSA levels.

  4. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Valentini, Anna Lia, E-mail: alvalentini@rm.unicatt.it [Department of Bioimaging and Radiological Sciences, Section of Radiology, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy); Gui, Benedetta [Department of Bioimaging and Radiological Sciences, Section of Radiology, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy); D' Agostino, Giuseppe Roberto; Mattiucci, Giancarlo [Department of Bioimaging and Radiological Sciences, Section of Radiotherapy, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy); Clementi, Valeria [Clinical Science Development Group, GE Healthcare, Milan (Italy); Di Molfetta, Ippolita Valentina [Department of Bioimaging and Radiological Sciences, Section of Radiology, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy); Bonomo, Pierluigi [OU Clinic Radiobiology, I.F.C.A. Florence (Italy); Mantini, Giovanna [Department of Bioimaging and Radiological Sciences, Section of Radiotherapy, Universita Cattolica del Sacro Cuore di Roma, Milan (Italy)

    2012-11-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  5. Associations between aerobic exercise levels and physical and mental health outcomes in men with bone metastatic prostate cancer: a cross-sectional investigation.

    Science.gov (United States)

    Zopf, E M; Newton, R U; Taaffe, D R; Spry, N; Cormie, P; Joseph, D; Chambers, S K; Baumann, F T; Bloch, W; Galvão, D A

    2016-09-20

    Cancer patients with bone metastases have previously been excluded from participation in physical activity programmes due to concerns of skeletal fractures. Our aim was to provide initial information on the association between physical activity levels and physical and mental health outcomes in prostate cancer patients with bone metastases. Between 2012 and 2015, 55 prostate cancer patients (mean age 69.7 ± 8.3; BMI 28.6 ± 4.0) with bone metastases (58.2% >2 regions affected) undertook assessments for self-reported physical activity, physical and mental health outcomes (SF-36), objective physical performance measures and body composition by DXA. Sixteen men (29%) met the current aerobic exercise guidelines for cancer survivors, while 39 (71%) reported lower aerobic exercise levels. Men not meeting aerobic exercise guidelines had lower physical functioning (p = .004), role functioning (physical and emotional) (p health scores (p = .014) as well all lower measures of physical performance (p exercise are associated with reduced physical and mental health outcomes in prostate cancer patients with bone metastases. While previous research has focused primarily in those with non-metastatic disease, our initial results suggest that higher levels of aerobic exercise may preserve physical and mental health outcomes in prostate cancer patients with bone metastases.

  6. Potential utility of cancer-specific biomarkers for assessing response to hormonal treatments in metastatic prostate cancer

    NARCIS (Netherlands)

    Schalken, J.; Dijkstra, S.; Baskin-Bey, E.; Oort, I. van

    2014-01-01

    Prostate cancer is the second leading cause of cancer death in men and there is an urgent clinical need to improve its detection and treatment. The introduction of prostate-specific antigen (PSA) as a biomarker for prostate cancer several decades ago represented an important step forward in our abil

  7. Targeting receptor for advanced glycation end products (RAGE) expression induces apoptosis and inhibits prostate tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Elangovan, Indira; Thirugnanam, Sivasakthivel; Chen, Aoshuang; Zheng, Guoxing [Department of Biomedical Sciences, University of Illinois, College of Medicine, Rockford, IL 61107 (United States); Bosland, Maarten C.; Kajdacsy-Balla, Andre [Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612 (United States); Gnanasekar, Munirathinam, E-mail: mgnanas@uic.edu [Department of Biomedical Sciences, University of Illinois, College of Medicine, Rockford, IL 61107 (United States)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Targeting RAGE by RNAi induces apoptosis in prostate cancer cells. Black-Right-Pointing-Pointer Silencing RAGE expression abrogates rHMGB1 mediated cell proliferation. Black-Right-Pointing-Pointer Down regulation of RAGE by RNAi inhibits PSA secretion of prostate cancer cells. Black-Right-Pointing-Pointer Knock down of RAGE abrogates prostate tumor growth in vivo. Black-Right-Pointing-Pointer Disruption of RAGE expression in prostate tumor activates death receptors. -- Abstract: Expression of receptor for advanced glycation end products (RAGE) plays a key role in the progression of prostate cancer. However, the therapeutic potential of targeting RAGE expression in prostate cancer is not yet evaluated. Therefore in this study, we have investigated the effects of silencing the expression of RAGE by RNAi approach both in vitro and in vivo. The results of this study showed that down regulation of RAGE expression by RNAi inhibited the cell proliferation of androgen-dependent (LNCaP) and androgen-independent (DU-145) prostate cancer cells. Furthermore, targeting RAGE expression resulted in apoptotic elimination of these prostate cancer cells by activation of caspase-8 and caspase-3 death signaling. Of note, the levels of prostate specific antigen (PSA) were also reduced in LNCaP cells transfected with RAGE RNAi constructs. Importantly, the RAGE RNAi constructs when administered in nude mice bearing prostate tumors, inhibited the tumor growth by targeting the expression of RAGE, and its physiological ligand, HMGB1 and by up regulating death receptors DR4 and DR5 expression. Collectively, the results of this study for the first time show that targeting RAGE by RNAi may be a promising alternative therapeutic strategy for treating prostate cancer.

  8. The importance of combined radiation and endocrine therapy in locally advanced prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Phillip J Gray; William U Shipley

    2012-01-01

    The management of all stages of prostate cancer has become an increasingly complex task as new treatment paradigms are tested and the results of large randomized studies become available.Despite these advances,prostate cancer remains the second leading cause of eancer death and the seventh overall cause of death in men in the United States.1 The advent of prostate-specific antigen (PSA) testing in the 1980s resulted in a significant downward stage migration such that many men now present with the earliest and most curable form of the disease.2,3 Despite this fact,high-risk locally advanced prostate cancer remains a common and complex problem facing clinicians across the world.

  9. Dietary flavonoid intake, black tea consumption, and risk of overall and advanced stage prostate cancer.

    Science.gov (United States)

    Geybels, Milan S; Verhage, Bas A J; Arts, Ilja C W; van Schooten, Frederik J; Goldbohm, R Alexandra; van den Brandt, Piet A

    2013-06-15

    Flavonoids are natural antioxidants found in various foods, and a major source is black tea. Some experimental evidence indicates that flavonoids could prevent prostate cancer. We investigated the associations between flavonoid intake, black tea consumption, and prostate cancer risk in the Netherlands Cohort study, which includes 58,279 men who provided detailed baseline information on several cancer risk factors. From 1986 to 2003, 3,362 prostate cancers were identified, including 1,164 advanced (stage III/IV) cancers. Cox proportional hazards regression using the case-cohort approach was used to estimate hazard ratios and 95% confidence intervals. Intake of total catechin, epicatechin, kaempferol, and myricetin and consumption of black tea were associated with a decreased risk of stage III/IV or stage IV prostate cancer. Hazard ratios of stage III/IV and stage IV prostate cancer for the highest versus the lowest category of black tea consumption (≥5 versus ≤1 cups/day) were 0.75 (95% confidence interval: 0.59, 0.97) and 0.67 (95% confidence interval: 0.50, 0.91), respectively. No associations were observed for overall and nonadvanced prostate cancer. In conclusion, dietary flavonoid intake and black tea consumption were associated with a decreased risk of advanced stage prostate cancer.

  10. A structured review of health utility measures and elicitation in advanced/metastatic breast cancer

    Directory of Open Access Journals (Sweden)

    Hao Y

    2016-06-01

    Full Text Available Yanni Hao,1 Verena Wolfram,2 Jennifer Cook2 1Novartis Pharmaceuticals, East Hanover, NJ, USA; 2Adelphi Values, Bollington, UK Background: Health utilities are increasingly incorporated in health economic evaluations. Different elicitation methods, direct and indirect, have been established in the past. This study examined the evidence on health utility elicitation previously reported in advanced/metastatic breast cancer and aimed to link these results to requirements of reimbursement bodies. Methods: Searches were conducted using a detailed search strategy across several electronic databases (MEDLINE, EMBASE, Cochrane Library, and EconLit databases, online sources (Cost-effectiveness Analysis Registry and the Health Economics Research Center, and web sites of health technology assessment (HTA bodies. Publications were selected based on the search strategy and the overall study objectives. Results: A total of 768 publications were identified in the searches, and 26 publications, comprising 18 journal articles and eight submissions to HTA bodies, were included in the evidence review. Most journal articles derived utilities from the European Quality of Life Five-Dimensions questionnaire (EQ-5D. Other utility measures, such as the direct methods standard gamble (SG, time trade-off (TTO, and visual analog scale (VAS, were less frequently used. Several studies described mapping algorithms to generate utilities from disease-specific health-related quality of life (HRQOL instruments such as European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (EORTC QLQ-C30, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire – Breast Cancer 23 (EORTC QLQ-BR23, Functional Assessment of Cancer Therapy – General questionnaire (FACT-G, and Utility-Based Questionnaire-Cancer (UBQ-C; most used EQ-5D as the reference. Sociodemographic factors that affect health utilities, such as age, sex

  11. Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide

    DEFF Research Database (Denmark)

    Anand, Aseem; Morris, Michael J; Larson, Steven M;

    2016-01-01

    BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the a......BACKGROUND: Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength......-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall...... alone (C-index 0.73), p = 0.041. CONCLUSIONS: The upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated...

  12. Identification of Prostate Cancer Prognostic Markers

    Science.gov (United States)

    2015-10-01

    targets. Specific aims are: 1) To profile bone metastasis samples to identify genomic alterations of PCa metastases that can be retrieved in their...Current markers - preoperative serum prostate specific antigen (PSA) levels, tumor stage and biopsy Gleason score (GS) - cannot accurately predict...individual patient outcome. For advanced and metastatic disease there is no curative treatment. Genomic profiling studies have identified specific genomic

  13. [Prostate cancer stem cells: advances in current research].

    Science.gov (United States)

    Wu, Gang; Wu, Deng-long

    2015-02-01

    Prostate cancer is one of the most common malignancies threatening men's health, and the mechanisms underlying its initiation and progression are poorly understood. Last decade has witnessed encouraging progress in the studies of prostate cancer stem cells (PCSCs), which are considered to play important roles in tumor initiation, recurrence and metastasis, castration resistance, and drug resistance. Therefore, a deeper insight into PCSCs is of great significance for the successful management of prostate cancer. This article presents an overview on the location, origin, and markers of PCSCs as well as their potential correlation with tumor metastasis and castration resistance.

  14. Degarelix 240/80 mg: a new treatment option for patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Boccon-Gibod, Laurent; Iversen, Peter; Persson, Bo-Eric

    2009-01-01

    levels that can lead to clinical flare in patients with advanced disease. Degarelix (Firmagon is a new GnRH blocker that has recently been approved by the EMEA and US FDA for the treatment of men with hormone-sensitive advanced prostate cancer. In this article, we briefly review the Phase III trial data...

  15. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Tyrrell, C J; Kaisary, A V

    2000-01-01

    Nonsteroidal antiandrogen monotherapy may be a treatment option for some patients with advanced prostate cancer. We report a survival and safety update from an analysis of 2 studies in which patients with nonmetastatic (M0) locally advanced disease were treated with either 150 mg. bicalutamide...

  16. Cysteine (C-x-C receptor 4 undergoes transportin 1-dependent nuclear localization and remains functional at the nucleus of metastatic prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Ayesha S Don-Salu-Hewage

    Full Text Available The G-protein coupled receptor (GPCR, Cysteine (C-X-C Receptor 4 (CXCR4, plays an important role in prostate cancer metastasis. CXCR4 is generally regarded as a plasma membrane receptor where it transmits signals that support transformation, progression and eventual metastasis. Due to the central role of CXCR4 in tumorigenesis, therapeutics approaches such as antagonist and monoclonal antibodies have focused on receptors that exist on the plasma membrane. An emerging concept for G-protein coupled receptors is that they may localize to and associate with the nucleus where they retain function and mediate nuclear signaling. Herein, we demonstrate that CXCR4 associated with the nucleus of malignant prostate cancer tissues. Likewise, expression of CXCR4 was detected in nuclear fractions among several prostate cancer cell lines, compared to normal prostate epithelial cells. Our studies identified a nuclear pool of CXCR4 and we defined a nuclear transport pathway for CXCR4. We reveal a putative nuclear localization sequence (NLS, 'RPRK', within CXCR4 that contributed to nuclear localization. Additionally, nuclear CXCR4 interacted with Transportinβ1 and Transportinβ1-binding to CXCR4 promoted its nuclear translocation. Importantly, Gαi immunoprecipitation and calcium mobilization studies indicated that nuclear CXCR4 was functional and participated in G-protein signaling, revealing that the nuclear pool of CXCR4 retained function. Given the suggestion that functional, nuclear CXCR4 may be a mechanism underlying prostate cancer recurrence, increased metastatic ability and poorer prognosis after tumors have been treated with therapy that targets plasma membrane CXCR4, these studies addresses a novel mechanism of nuclear signaling for CXCR4, a novel mechanism of clinical targeting, and demonstrate an active nuclear pool that provides important new information to illuminate what has been primarily clinical reports of nuclear CXCR4.

  17. The measurement of response shift in patients with advanced prostate cancer and their partners

    Directory of Open Access Journals (Sweden)

    O'Boyle Ciaran

    2005-03-01

    Full Text Available Abstract Background There is increasing evidence to support the phenomenon of response shift (RS in quality of life (QoL studies, with many current QoL measures failing to allow for this. If significant response shift occurs amongst prostate cancer patients, it will be necessary to allow for this in the design of future clinical research and to reassess the conclusions of previous studies that have not allowed for this source of bias. This study therefore aimed to assess the presence of RS and psychosocial morbidity in patients with advanced prostate cancer and their partners. Methods 55 consecutive advanced prostate cancer patients and their partners completed the Prostate Cancer Patient & Partner questionnaire (PPP, shortly after diagnosis and again at 3 months and 6 months. At the follow-up visits, both patients and partners also completed a then-test in order to assess RS. Results Partners consistently showed greater psychological morbidity than patients in relation to the prostate cancer. This was most marked on the General Cancer Distress (GCD subscale (p Conclusion These results suggest the presence of RS in patients with advanced prostate cancer and their partners, with higher levels of psychosocial morbidity noted amongst partners. This is the first study to identify RS in partners and calls into question the interpretation of all studies assessing changes in QoL that fail to allow for this phenomenon.

  18. Dosimetry for {sup 177}Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Delker, Andreas; Fendler, Wolfgang Peter; Brunegraf, Anika; Gosewisch, Astrid; Gildehaus, Franz Josef; Bartenstein, Peter; Boening, Guido [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Kratochwil, Clemens; Haberkorn, Uwe [Heidelberg University Hospital, Department for Nuclear Medicine, Heidelberg (Germany); Tritschler, Stefan; Stief, Christian Georg [Ludwig-Maximilians-University of Munich, Department of Urology, Munich (Germany); Kopka, Klaus [German Cancer Research Center (dkfz), Division of Radiopharmaceutical Chemistry, Heidelberg (Germany)

    2016-01-15

    Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand {sup 177}Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) {sup 177}Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with {sup 177}Lu-DKFZ-PSMA-617. We suggest that {sup 177}Lu-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour

  19. Detection of live circulating tumor cells by a class of near-infrared heptamethine carbocyanine dyes in patients with localized and metastatic prostate cancer.

    Science.gov (United States)

    Shao, Chen; Liao, Chun-Peng; Hu, Peizhen; Chu, Chia-Yi; Zhang, Lei; Bui, Matthew H T; Ng, Christopher S; Josephson, David Y; Knudsen, Beatrice; Tighiouart, Mourad; Kim, Hyung L; Zhau, Haiyen E; Chung, Leland W K; Wang, Ruoxiang; Posadas, Edwin M

    2014-01-01

    Tumor cells are inherently heterogeneous and often exhibit diminished adhesion, resulting in the shedding of tumor cells into the circulation to form circulating tumor cells (CTCs). A fraction of these are live CTCs with potential of metastatic colonization whereas others are at various stages of apoptosis making them likely to be less relevant to understanding the disease. Isolation and characterization of live CTCs may augment information yielded by standard enumeration to help physicians to more accurately establish diagnosis, choose therapy, monitor response, and provide prognosis. We previously reported on a group of near-infrared (NIR) heptamethine carbocyanine dyes that are specifically and actively transported into live cancer cells. In this study, this viable tumor cell-specific behavior was utilized to detect live CTCs in prostate cancer patients. Peripheral blood mononuclear cells (PBMCs) from 40 patients with localized prostate cancer together with 5 patients with metastatic disease were stained with IR-783, the prototype heptamethine cyanine dye. Stained cells were subjected to flow cytometric analysis to identify live (NIR(+)) CTCs from the pool of total CTCs, which were identified by EpCAM staining. In patients with localized tumor, live CTC counts corresponded with total CTC numbers. Higher live CTC counts were seen in patients with larger tumors and those with more aggressive pathologic features including positive margins and/or lymph node invasion. Even higher CTC numbers (live and total) were detected in patients with metastatic disease. Live CTC counts declined when patients were receiving effective treatments, and conversely the counts tended to rise at the time of disease progression. Our study demonstrates the feasibility of applying of this staining technique to identify live CTCs, creating an opportunity for further molecular interrogation of a more biologically relevant CTC population.

  20. Detection of live circulating tumor cells by a class of near-infrared heptamethine carbocyanine dyes in patients with localized and metastatic prostate cancer.

    Directory of Open Access Journals (Sweden)

    Chen Shao

    Full Text Available Tumor cells are inherently heterogeneous and often exhibit diminished adhesion, resulting in the shedding of tumor cells into the circulation to form circulating tumor cells (CTCs. A fraction of these are live CTCs with potential of metastatic colonization whereas others are at various stages of apoptosis making them likely to be less relevant to understanding the disease. Isolation and characterization of live CTCs may augment information yielded by standard enumeration to help physicians to more accurately establish diagnosis, choose therapy, monitor response, and provide prognosis. We previously reported on a group of near-infrared (NIR heptamethine carbocyanine dyes that are specifically and actively transported into live cancer cells. In this study, this viable tumor cell-specific behavior was utilized to detect live CTCs in prostate cancer patients. Peripheral blood mononuclear cells (PBMCs from 40 patients with localized prostate cancer together with 5 patients with metastatic disease were stained with IR-783, the prototype heptamethine cyanine dye. Stained cells were subjected to flow cytometric analysis to identify live (NIR(+ CTCs from the pool of total CTCs, which were identified by EpCAM staining. In patients with localized tumor, live CTC counts corresponded with total CTC numbers. Higher live CTC counts were seen in patients with larger tumors and those with more aggressive pathologic features including positive margins and/or lymph node invasion. Even higher CTC numbers (live and total were detected in patients with metastatic disease. Live CTC counts declined when patients were receiving effective treatments, and conversely the counts tended to rise at the time of disease progression. Our study demonstrates the feasibility of applying of this staining technique to identify live CTCs, creating an opportunity for further molecular interrogation of a more biologically relevant CTC population.

  1. GPNMB/OA protein increases the invasiveness of human metastatic prostate cancer cell lines DU145 and PC3 through MMP-2 and MMP-9 activity

    Energy Technology Data Exchange (ETDEWEB)

    Fiorentini, Chiara; Bodei, Serena; Bedussi, Francesca; Fragni, Martina; Bonini, Sara Anna [Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia (Italy); Simeone, Claudio; Zani, Danilo [Division of Urology, Department of Surgery, Radiology and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia (Italy); Berruti, Alfredo [Medical Oncology, Department of Surgery, Radiology, and Public Health, University of Brescia, P.le Spedali Civili 1, 25124 Brescia (Italy); Missale, Cristina; Memo, Maurizio; Spano, PierFranco [Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia (Italy); Sigala, Sandra, E-mail: sigala@med.unibs.it [Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25124 Brescia (Italy)

    2014-04-15

    Non-metastatic glycoprotein melanoma protein B (GPNMB), also known as osteoactivin (OA) is expressed in a wide array of tumors and represents an emerging target for drug development. In this study, we investigated the role of GPNMB/OA in the progression of human metastatic DU145 and PC3 prostate cancer cells. GPNMB/OA contribution in PCa malignant phenotype has been analyzed by small interfering RNA-induced GPNMB/OA silencing. We found that following GPNMB/OA silencing the migration capability of both DU145 and PC3 cells, evaluated by using in vitro invasivity assay, as well as the metalloproteinases MMP-2 and MMP-9 activity were equally strongly inhibited. By contrast knocking down GPNMB/OA weakly attenuated cell proliferation rate of DU145, an effect that paralleled with an increase number of apoptotic cells. However, PC3 cell growth seems to be not affected by GPNMB/OA. Together, these data reveal that GPNMB/OA acts as a critical molecular mediator promoting the acquisition of the more aggressive, pro-metastatic phenotype distinctive of human DU145 and PC3 cell lines. - Highlights: • GPNMB/OA expression correlates with DU145 and PC3 cells malignant phenotype. • GPNMB/OA silencing affects the migration capability of both DU145 and PC3 cells. • GPNMB/OA increases invasiveness by up-regulating MMPs activity. • GPNMB/OA promotes DU145 and PC3 cells progression into a more aggressive phenotype.

  2. Targeted Approach to Overcoming Treatment Resistance in Advanced Prostate Cancer

    Science.gov (United States)

    2015-09-01

    nitrogen) aliquot of PC3 cells (ATCC: human prostate adenocarcinoma). 2. Disperse into 75 cm2 flask containing RPMI 1640 media supplemented with 10% fetal ...compound #88 shows high cell killing efficacy in prostate cancer cell lines, including taxol resistant cells that stems from the induction of apoptosis...approach engages computational modeling to identify compounds that target a specific, mismatch repair protein-­‐dependent cell death pathway. A

  3. New strategies in metastatic melanoma: oncogene-defined taxonomy leads to therapeutic advances.

    Science.gov (United States)

    Flaherty, Keith T; Fisher, David E

    2011-08-01

    The discovery of BRAF and KIT mutations provided the first basis for a molecular classification of cutaneous melanoma on therapeutic grounds. As BRAF-targeted therapy quickly moves toward regulatory approval and incorporation as standard therapy for patients with metastatic disease, proof of concept has also been established for targeting mutated KIT in melanoma. NRAS mutations have long been known to be present in a subset of melanomas and represent an elusive subgroup for targeted therapies. Matching patient subgroups defined by genetic aberrations in the phosphoinositide 3-kinase and p16/cyclin dependent kinase 4 (CDK4) pathways with appropriate targeted therapies has not yet been realized. And, an increasing understanding of lineage-specific transcriptional regulators, most notably MITF, and how they may play a role in melanoma pathophysiology, has provided another axis to approach with therapies. The foundation has been established for individual oncogene targeting, and current investigations seek to understand the intersection of these susceptibilities and other described potential targets and pathways. The melanoma field stands poised to take the lead among cancer subtypes in advancing combination therapy strategies that simultaneously target multiple biologic underpinnings of the disease.

  4. Alternative temozolomide dosing regimens and novel combinations for the treatment of advanced metastatic melanoma

    Directory of Open Access Journals (Sweden)

    Wen-Jen Hwu

    2011-12-01

    Full Text Available Over the past 30 years, there has been no significant improvement in treatment outcomes for patients with advanced stage IV metastatic melanoma, and prognosis remains poor. Melanoma is known to be responsive to immunomodulatory agents, to be a highly vascular tumor, and to be fairly resistant to standard cytotoxic chemotherapy. Ongoing research is attempting to find novel combinations that may have therapeutic synergy. Alternative dosedense schedules of temozolomide appear promising and are being actively investigated, based on their potential to overcome chemoresistance to alkylating agents and the proven activity of temozolomide in the brain. Outcomes of studies investigating single-agent temozolomide suggest that it has activity similar to single-agent dacarbazine. Other studies combining temozolomide with either interferon- alfa or thalidomide suggest that the addition of these immunomodulatory agents to temozolomide improves response rates and may improve overall survival. The best results have been achieved with the extended, daily, dosedense temozolomide regimen. Further research is needed to determine the optimal temozolomide regimen and best combination approach

  5. Effects of androgen deprivation therapy and bisphosphonate treatment on bone in patients with metastatic castration-resistant prostate cancer: results from the University of Washington Rapid Autopsy Series.

    Science.gov (United States)

    Morrissey, Colm; Roudier, Martine P; Dowell, Alex; True, Lawrence D; Ketchanji, Melanie; Welty, Christopher; Corey, Eva; Lange, Paul H; Higano, Celestia S; Vessella, Robert L

    2013-02-01

    Qualitative and quantitative bone features were determined in nondecalcified and decalcified bone from 20 predetermined bone sites in each of 44 patients who died with castration-resistant prostate cancer (CRPC), some of which received bisphosphonate treatment (BP) in addition to androgen-deprivation therapy (ADT). Thirty-nine of the 44 patients (89%) had evidence of bone metastases. By histomorphometric analysis, these bone metastases were associated with a range of bone responses from osteoblastic to osteolytic with a wide spectrum of bone responses often seen within an individual patient. Overall, the average bone volume/tissue volume (BV/TV) was 25.7%, confirming the characteristic association of an osteoblastic response to prostate cancer bone metastasis when compared with the normal age-matched weighted mean BV/TV of 14.7%. The observed new bone formation was essentially woven bone, and this was a localized event. In comparing BV/TV at metastatic sites between patients who had received BP treatment and those who had not, there was a significant difference (28.6% versus 19.3%, respectively). At bone sites that were not invaded by tumor, the average BV/TV was 10.1%, indicating significant bone loss owing to ADT that was not improved (11%) in those patients who had received BPs. Surprisingly, there was no significant difference in the number of osteoclasts present at the metastatic sites between patients treated or not treated with BPs, but in bone sites where the patient had been treated with BPs, giant osteoclasts were observed. Overall, 873 paraffin-embedded specimens and 661 methylmethacrylate-embedded specimens were analyzed. Our results indicate that in CRPC patients, ADT induces serious bone loss even in patients treated with BP. Furthermore, in this cohort of patients, BP treatment increased BV and did not decrease the number of osteoclasts in prostate cancer bone metastases compared with bone metastases from patients who did not receive BP.

  6. Sequencing therapy in advanced prostate cancer: focus on sipuleucel-T.

    Science.gov (United States)

    Quinn, David I; Vaishampayan, Ulka; Higano, Celestia S; Lin, Daniel W; Shore, Neal D; Beer, Tomasz M

    2014-01-01

    Immunotherapies such as sipuleucel-T present new and unique challenges for the optimal timing and sequencing of therapies for metastatic castration-resistant prostate cancer (mCRPC). Key considerations for the sequencing of sipuleucel-T are its unique proposed mechanism of action, the time required to generate a clinically relevant immune response, and the observed efficacy in Phase III trials in 'early' or asymptomatic or minimally symptomatic mCRPC. There are three broad timing and sequencing options for sipuleucel-T in patients with rising prostate-specific antigen and radiologic evidence of disease: immediately after androgen-deprivation therapy failure, after failure of secondary hormonal maneuvers, or after chemotherapy. There are several other agents in Phase III development in mCRPC and any future approvals will impact on the current treatment algorithm, and raise further questions regarding how to optimize sequencing and timing of therapies for better clinical outcomes.

  7. Serum testosterone as a prognostic factor in patients with advanced prostatic carcinoma

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Christensen, I J

    1994-01-01

    In 245 patients with previously untreated advanced carcinoma of the prostate, serum concentrations of testosterone have been measured before androgen deprivation therapy, and patients were divided in quartiles according to their serum concentration. Pretreatment level of serum testosterone was co...... parameters suggest that low serum testosterone merely is a consequence of the advanced malignancy rather than a causative factor in the pathogenesis of prostatic cancer.......In 245 patients with previously untreated advanced carcinoma of the prostate, serum concentrations of testosterone have been measured before androgen deprivation therapy, and patients were divided in quartiles according to their serum concentration. Pretreatment level of serum testosterone...... was confirmed as having significant prognostic value on progression-free, overall, and cancer-specific survival, and the hazard ratios of lower quartiles compared to the upper quartile for these endpoints were 2.3, 2.1, and 2.0, respectively. However, correlations with symptomatology and other pretreatment...

  8. Targeting Prostate Cancer for Gene Therapy Utilizing Lentivirus and Oncolytic VSV Virus

    Science.gov (United States)

    2010-04-01

    not yet published. 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer is the most commonly diagnosed non- skin carcinoma and o ne o f the...surgery or radiotherapy . Presently there are no therapies available for advanced and metastatic prostate cancer, thus the emergence of new targeted...aque a ssay w hich s howed a hi gher concentration of replicating vi rus in prostates of PTEN -/- mice while sparing normal cells in control mice

  9. Role of targeted therapy in the treatment of advanced prostate cancer.

    Science.gov (United States)

    Fizazi, Karim; Sternberg, Cora N; Fitzpatrick, John M; Watson, R William; Tabesh, Majid

    2010-03-01

    Over the past decade, the treatment of advanced prostate cancer has developed significantly, and perhaps the most dramatic shift came in 2004 with the demonstration that docetaxel-based chemotherapy significantly improved overall survival in patients with castration-resistant prostate cancer. This led to a significant expansion of the role of chemotherapy in the management of prostate cancer. In addition, there is now considerable progress being made in the development of more effective antiandrogens, cytochrome P17 inhibitors, novel chemotherapy regimens, targeted therapies, and immunotherapies that can complement existing therapies and may soon become integrated into the treatment paradigm. Progress in our understanding of molecular signalling pathways that play an important role in prostate cancer has stimulated the investigation of targeted therapies, including antiangiogenic agents, bone-targeted agents, and specific inhibitors of key signalling molecules and chaperone proteins. For the most part, targeted agents are being combined with chemotherapy, similar to the approach taken in other solid tumours. Various therapeutic vaccine strategies also appear to have potential in the treatment of advanced prostate cancer. However, the development of new approaches to the treatment of prostate cancer presents many challenges that will demand collaboration and consensus building with respect to biomarkers for patient selection, clinical endpoints, and trial designs.

  10. Combined inhibition of epidermal growth factor receptor and cyclooxygenase-2 leads to greater anti-tumor activity of docetaxel in advanced prostate cancer.

    Directory of Open Access Journals (Sweden)

    Jianzhong Lin

    Full Text Available The epidermal growth factor receptor (EGFR and cyclooxygenase-2(COX-2 play a critical role in disease progression, relapse and therapeutic resistance of advanced prostate cancer (PCa. In this paper, we evaluated, for the first time, the therapeutic benefit of blocking EGRF and/or COX-2 (using gefitinib and NS-398, respectively in terms of improving the efficacy of the conventional clinical chemotherapeutic drug docetaxel in vitro and vivo. We showed that EGFR and COX-2 expression was higher in metastatic than non-metastatic PCa tissues and cells. Docetaxel, alone or in combination with gefitinib or NS-398, resulted in a small decrease in cell viability. The three drug combination decreased cell viability to a greater extent than docetaxel alone or in combination with gefitinib or NS-398. Docetaxel resulted in a modest increase in apoptotic cell in metastatic and non-metastatic cell lines. NS-398 markedly enhanced docetaxel-induced cell apoptosis. The combination of the three drugs caused even more marked apoptosis and resulted in greater suppression of invasive potential than docetaxel alone or in association with gefitinib or NS-398. The combination of all three drugs also resulted in a more marked decrease in NF-ΚB, MMP-9 and VEGF levels in PC-3M cells. These in vitro findings were supported by in vivo studies showing that docetaxel in combination with gefitinib and NS-398 was significantly more effective than any individual agent. Based on previous preclinical research, we conclude that simultaneously blocking EGFR and COX-2 by gefitinib and NS-398 sensitizes advanced PCa cells to docetaxel-induced cytotoxicity.

  11. HIGH-INTENSITY FOCUSED ULTRASOUND ABLATION OF PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    L. V. Shaplygin

    2014-01-01

    Full Text Available In this study the results of retrospective analysis of treatment of 311 patients in Samara Oncology Center in 2008–2011 with locally advanced prostate cancer are presented. According to the received treatment patients were divided into 3 groups: 103 underwent HIFU, 101 patients had a course of EBRT, 107 patients received only hormone therapy (HT. Overall survival in patients with locally advanced prostate cancer after HIFU therapy was 86.2 %, after EBRT and HT – 66.3% and 18.1 %, respectively. These data indicate a high clinical efficacy of ultrasound ablation. 

  12. Degarelix 240/80 mg: a new treatment option for patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Boccon-Gibod, L.; Iversen, P.; Persson, B.E.;

    2009-01-01

    levels that can lead to clinical flare in patients with advanced disease. Degarelix (Firmagon is a new GnRH blocker that has recently been approved by the EMEA and US FDA for the treatment of men with hormone-sensitive advanced prostate cancer. In this article, we briefly review the Phase III trial data......Gonadotrophin-releasing hormone (GnRH) receptor blockers (antagonists) are the latest addition to the hormonal therapy armamentarium for patients with prostate cancer. In contrast to the GnRH agonists, GnRH blockers have an immediate onset of action and do not cause an initial surge in testosterone...

  13. Long-term results of Danish Prostatic Cancer Group trial 86. Goserelin acetate plus flutamide versus orchiectomy in advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, P; Rasmussen, F; Klarskov, Peter;

    1993-01-01

    In a multicenter trial conducted by the Danish Prostatic Cancer Group, 264 patients with advanced prostate cancer were randomized either to undergo bilateral orchiectomy or to receive combination treatment with goserelin acetate and flutamide. This report is an update of that study, covering...... of goserelin and flutamide was not clinically superior to bilateral orchiectomy in the treatment of advanced prostate cancer....... a median follow-up for survival of 57 months. Of 262 patients who were evaluated, 208 have died. As noted in earlier analyses of this study, no differences in time to progression and cause-specific and overall survival could be identified between the two treatment groups. In conclusion, the combination...

  14. Advanced prostate cancer – patient survival and potential impact of enzalutamide and other emerging therapies

    Directory of Open Access Journals (Sweden)

    Patel NK

    2014-08-01

    Full Text Available Nihar K Patel, Antoine Finianos, Kristen D Whitaker, Jeanny B Aragon-Ching Department of Medicine, Division of Hematology and Oncology, George Washington University Medical Center, Washington, DC, USA Abstract: The advent of exponential growth of novel agents tested and approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC has brought about a need for understanding of the mechanism of action, side-effects, and clinical efficacy of these drugs as they relate to these patients. This review will provide a synopsis of the treatment landscape in mCRPC as varying agents such as abiraterone acetate, cabazitaxel, sipuleucel-T, radium, and selected emerging agents are presented. A distinct focus on the utilization of enzalutamide, its mechanism of action, key pivotal trials that brought about its US Food and Drug Administration approval, as well as patient-focused perspectives and clinical implications are discussed herein. Keywords: metastatic castration-resistant prostate cancer, enzalutamide, systemic therapies

  15. Upregulation of vascular endothelial growth factor by cobalt chloride-simulated hypoxia is mediated by persistent induction of cyclooxygenase-2 in a metastatic human prostate cancer cell line.

    Science.gov (United States)

    Liu, X H; Kirschenbaum, A; Yao, S; Stearns, M E; Holland, J F; Claffey, K; Levine, A C

    1999-01-01

    Upregulation of vascular endothelial growth factor (VEGF) expression induced by hypoxia is crucial event leading to neovascularization. Cyclooxygenase-2, an inducible enzyme that catalyzes the formation of prostaglandins (PGs) from arachidonic acid, has been demonstrated to be induced by hypoxia and play role in angiogenesis and metastasis. To investigate the potential effect of COX-2 on hypoxia-induced VEGF expression in prostate cancer. We examined the relationship between COX-2 expression and VEGF induction in response to cobalt chloride (CoCl2)-simulated hypoxia in three human prostate cancer cell lines with differing biological phenotypes. Northern blotting and ELISA revealed that all three tested cell lines constitutively expressed VEGF mRNA, and secreted VEGF protein to different degrees (LNCaP > PC-3 > PC3ML). However, these cell lines differed in the ability to produce VEGF in the presence of CoCl2-simulated hypoxia. CoCl2 treatment resulted in 40% and 75% increases in VEGF mRNA, and 50% and 95% in protein secretion by LNCaP and PC-3 cell lines, respectively. In contrast, PC-3ML cell line, a PC-3 subline with highly invasive, metastatic phenotype, exhibits a dramatic upregulation of VEGF, 5.6-fold in mRNA and 6.3-fold in protein secretion after treatment with CoCl2. The upregulation of VEGF in PC-3ML cells is accompanied by a persistent induction of COX-2 mRNA (6.5-fold) and protein (5-fold). Whereas COX-2 expression is only transiently induced in PC-3 cells and not affected by CoCl2 in LNCaP cells. Moreover, the increases in VEGF mRNA and protein secretion induced by CoCl2 in PC-3ML cells were significantly suppressed following exposure to NS398, a selective COX-2 inhibitor. Finally, the effect of COX-2 inhibition on CoCl2-induced VEGF production was reversed by the treatment with exogenous PGE2. Our data demonstrate that VEGF induction by cobalt chloride-simulated hypoxia is maintained by a concomitant, persistent induction of COX-2 expression and

  16. New considerations for ADT in advanced prostate cancer and the emerging role of GnRH antagonists.

    Science.gov (United States)

    Shore, N D; Abrahamsson, P-A; Anderson, J; Crawford, E D; Lange, P

    2013-03-01

    Androgen deprivation therapy (ADT) is first-line treatment for metastatic prostate cancer (PCa). Gonadotrophin-releasing hormone (GnRH) agonists are the most commonly used ADT but have several theoretical physiologic disadvantages (e.g. initial testosterone surge, potential microsurges upon repeat administration). Testosterone surge delays the intended serologic endpoint of testosterone suppression and may exacerbate clinical symptoms. GnRH antagonists were developed with a view toward overcoming these potential adverse physiologic events. This review evaluates GnRH agonists and antagonists, assessing the potential future role of antagonists in PCa and strategies to minimize ADT adverse events (AEs). Evidence was identified via PubMed search (by GnRH agent and other ADT-related terms), from review article bibliographies, and authors' therapy area knowledge, with articles included by author consensus. Degarelix shows similar efficacy to a GnRH agonist in achieving and maintaining castration, with faster onset and without testosterone surge/microsurges. Phase III data showed that, in the first treatment year, degarelix displayed a lower risk of PSA failure or death (composite endpoint), lower levels of the bone marker serum alkaline phosphatase (in baseline metastatic disease), and fewer musculoskeletal AEs than the agonist leuprolide. Also, crossing over from leuprolide to degarelix after 1 year reduced the risk of PSA failure or death. ADT displays an AE spectrum which can impact quality of life as well as causing significant morbidities. Strategies to improve ADT tolerability have become increasingly important including: a holistic management approach, improved diet and exercise, more specific monitoring to detect and prevent testosterone depletion toxicities, and intermittent ADT allowing hormonal recovery between treatment periods. Clinical studies suggest possible benefits of GnRH antagonists over agonists based on different mechanisms of action. Gn

  17. Prognostic impact of metastatic lymph node ratio in advanced gastric cancer from cardia and fundus

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the prognostic impact of the metastatic lymph node ratio (MLR) in advanced gastric cancer from the cardia and fundus. METHODS: Two hundred and thirty-six patients with gastric cancer from the cardia and fundus who underwent D2 curative resection were analyzed ret- rospectively. The correlations between MLR and the total lymph nodes, positive nodes and the total lymph nodes were analyzed respectively. The influence of MLR on the survival time of patients was determined with univariate Kaplan-Meier survival analysis and mul- tivariate Cox proportional hazard model analysis. And the multiple linear regression was used to identify the relation between MLR and the 5-year survival rate of the patients. RESULTS: The MLR did not correlate with the total lymph nodes resected (r = -0.093, P = 0.057). The 5-year overall survival rate of the whole cohort was 37.5%. Kaplan-Meier survival analysis identified that the following eight factors influenced the survival time of the patients postoperatively: gender (X2 = 4.26, P = 0.0389), tumor size (X2 = 18.48, P < 0.001), Borrmann type (X2 = 7.41, P = 0.0065), histological grade (X2 =5.07, P = 0.0243), pT category (X2 = 49.42, P < 0.001), pN category (X2 = 87.7, P < 0.001), total number of re- trieved lymph nodes (X2 = 8.22, P = 0.0042) and MLR (X2 = 34.3, P < 0.001). Cox proportional hazard model showed that tumor size (X2 = 7.985, P = 0.018), pT category (X2 = 30.82, P < 0.001) and MLR (X2 = 69.39, P < 0.001) independently influenced the prognosis. A linear correlation between MLR and the 5-year survival was statistically significant based on the multiple lin- ear regression (β = -0.63, P < 0.001). Hypothetically, the 5-year survival would surpass 50% when MLR was lower than 10%. CONCLUSION: The MLR is an independent prognostic factor for patients with advanced gastric cancer from the cardia and fundus. The decrease of MLR due to adequate number of total resected lymph nodes can improve the survival.

  18. Addressing the expected survival benefit for clinical trial design in metastatic castration-resistant prostate cancer: Sensitivity analysis of randomized trials.

    Science.gov (United States)

    Massari, Francesco; Modena, Alessandra; Ciccarese, Chiara; Pilotto, Sara; Maines, Francesca; Bracarda, Sergio; Sperduti, Isabella; Giannarelli, Diana; Carlini, Paolo; Santini, Daniele; Tortora, Giampaolo; Porta, Camillo; Bria, Emilio

    2016-02-01

    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.

  19. Efficient delivery of micro RNA to bone-metastatic prostate tumors by using aptamer-conjugated atelocollagen in vitro and in vivo.

    Science.gov (United States)

    Hao, Zhao; Fan, Wei; Hao, Jian; Wu, Xin; Zeng, Guo Qing; Zhang, Li Juan; Nie, Sui Feng; Wang, Xu Dong

    2016-01-01

    Bone is the primary site of skeletal metastasis in prostate cancer (PCa). Atelocollagen (ATE)-mediated siRNA delivery system can be used to silence endogenous genes involved in PCa metastatic tumor cell growth. However, we hope that the delivery system can target PCa cells to reduce damage to the bone tissue and improve the therapeutic effect. RNA aptamer (APT) A10-3.2 has been used as a ligand to target PCa cells that express prostate-specific membrane antigen (PSMA). APT was investigated as a PSMA-targeting ligand in the design of an ATE-based microRNA (miRNA; miR-15a and miR-16-1) vector to PCa bone metastasis. To observe the targeted delivery and transfection efficiency of ATE-APT in PSMA-overexpressing cells, luciferase activity and biodistribution of nanoparticles in Balb/c mice was analyzed. The anticancer effect of nanoparticles in vivo was investigated using the survival times of human PCa bone metastasis mice model. Luciferase assays of pGL-3 expression against PC3 (PSMA(-)) and LNCaP (PSMA(+)) cells showed that the transfection efficiency of the synthesized DNA/ATE-APT complex was higher than that of the DNA/ATE complex. The anticancer efficacy of miRNA/ATE-APT was superior to those of other treatments in vivo. This PSMA-targeted system may prove useful in widening the therapeutic window and allow for selective killing of PCa cells in bone metastatic foci.

  20. Overexpression of vascular endothelial growth factor C increases growth and alters the metastatic pattern of orthotopic PC-3 prostate tumors

    Directory of Open Access Journals (Sweden)

    Väänänen H Kalervo

    2009-10-01

    Full Text Available Abstract Background Prostate cancer metastasizes to regional lymph nodes and distant sites but the roles of lymphatic and hematogenous pathways in metastasis are not fully understood. Methods We studied the roles of VEGF-C and VEGFR3 in prostate cancer metastasis by blocking VEGFR3 using intravenous adenovirus-delivered VEGFR3-Ig fusion protein (VEGFR3-Ig and by ectopic expression of VEGF-C in PC-3 prostate tumors in nude mice. Results VEGFR3-Ig decreased the density of lymphatic capillaries in orthotopic PC-3 tumors (p p p p Conclusion The data suggest that even though VEGF-C/VEGFR3 pathway is primarily required for lymphangiogenesis and lymphatic metastasis, an increased level of VEGF-C can also stimulate angiogenesis, which is associated with growth of orthotopic prostate tumors and a switch from a primary pattern of lymph node metastasis to an increased proportion of metastases at distant sites.

  1. To Explore the Chinese Medicine Syndrome Types and Integrative Therapy from Clinical Relative Factors of Patients with Advanced Prostate Cancer

    Institute of Scientific and Technical Information of China (English)

    王伊光

    2009-01-01

    Current Situation and Problems of the Treatment in Advanced Prostate Cancer In recent years,the incidence of prostate cancer shows a rising trend in China with an increase of 70%and has been the first place in the growth rate of malignant tumor in the male reproductive system. Prostate cancer has become a serious threat to male senior's health.Because of the application of

  2. Impact of Bone-targeted Therapies in Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer Patients Treated with Abiraterone Acetate: Post Hoc Analysis of Study COU-AA-302

    Science.gov (United States)

    Saad, Fred; Shore, Neal; Van Poppel, Hendrik; Rathkopf, Dana E.; Smith, Matthew R.; de Bono, Johann S.; Logothetis, Christopher J.; de Souza, Paul; Fizazi, Karim; Mulders, Peter F.A.; Mainwaring, Paul; Hainsworth, John D.; Beer, Tomasz M.; North, Scott; Fradet, Yves; Griffin, Thomas A.; De Porre, Peter; Londhe, Anil; Kheoh, Thian; Small, Eric J.; Scher, Howard I.; Molina, Arturo; Ryan, Charles J.

    2016-01-01

    Background Metastatic castration-resistant prostate cancer (mCRPC) often involves bone, and bone-targeted therapy (BTT) has become part of the overall treatment strategy. Objective Investigation of outcomes for concomitant BTT in a post hoc analysis of the COU-AA-302 trial, which demonstrated an overall clinical benefit of abiraterone acetate (AA) plus prednisone over placebo plus prednisone in asymptomatic or mildly symptomatic chemotherapy-naïve mCRPC patients. Design, setting, and participants This report describes the third interim analysis (prespecified at 55% overall survival [OS] events) for the COU-AA-302 trial. Intervention Patients were grouped by concomitant BTT use or no BTT use. Outcome measurements and statistical analysis Radiographic progression-free survival and OS were coprimary end points. This report describes the third interim analysis (prespecified at 55% OS events) and involves patients treated with or without concomitant BTT during the COU-AA-302 study. Median follow-up for OS was 27.1 mo. Median time-to-event variables with 95% confidence intervals (CIs) were estimated using the Kaplan-Meier method. Adjusted hazard ratios (HRs), 95% CIs, and p values for concomitant BTT versus no BTT were obtained via Cox models. Results and limitations While the post hoc nature of the analysis is a limitation, superiority of AA and prednisone versus prednisone alone was demonstrated for clinical outcomes with or without BTT use. Compared with no BTT use, concomitant BTT significantly improved OS (HR 0.75; p = 0.01) and increased the time to ECOG deterioration (HR 0.75; p < 0.001) and time to opiate use for cancer-related pain (HR 0.80; p = 0.036). The safety profile of concomitant BTT with AA was similar to that reported for AA in the overall intent-to-treat population. Osteonecrosis of the jaw (all grade 1/2) with concomitant BTT use was reported in <3% of patients. Conclusions AA with concomitant BTT was safe and well tolerated in men with chemotherapy

  3. Inhibition of Notch pathway arrests PTEN-deficient advanced prostate cancer by triggering p27-driven cellular senescence

    Science.gov (United States)

    Revandkar, Ajinkya; Perciato, Maria Luna; Toso, Alberto; Alajati, Abdullah; Chen, Jingjing; Gerber, Hermeto; Dimitrov, Mitko; Rinaldi, Andrea; Delaleu, Nicolas; Pasquini, Emiliano; D'Antuono, Rocco; Pinton, Sandra; Losa, Marco; Gnetti, Letizia; Arribas, Alberto; Fraering, Patrick; Bertoni, Francesco; Nepveu, Alain; Alimonti, Andrea

    2016-01-01

    Activation of NOTCH signalling is associated with advanced prostate cancer and treatment resistance in prostate cancer patients. However, the mechanism that drives NOTCH activation in prostate cancer remains still elusive. Moreover, preclinical evidence of the therapeutic efficacy of NOTCH inhibitors in prostate cancer is lacking. Here, we provide evidence that PTEN loss in prostate tumours upregulates the expression of ADAM17, thereby activating NOTCH signalling. Using prostate conditional inactivation of both Pten and Notch1 along with preclinical trials carried out in Pten-null prostate conditional mouse models, we demonstrate that Pten-deficient prostate tumours are addicted to the NOTCH signalling. Importantly, we find that pharmacological inhibition of γ-secretase promotes growth arrest in both Pten-null and Pten/Trp53-null prostate tumours by triggering cellular senescence. Altogether, our findings describe a novel pro-tumorigenic network that links PTEN loss to ADAM17 and NOTCH signalling, thus providing the rational for the use of γ-secretase inhibitors in advanced prostate cancer patients. PMID:27941799

  4. New Action of Inhibin Alpha Subunit in Advanced Prostate Cancer

    Science.gov (United States)

    2010-02-01

    Preetika. Final Report Award: W81XWH-07-1-0112 25 Christofori, G., and Pepper , M. S. Vascular endothelial growth factor-C-mediated...prostate cancer. Clin Cancer Res., 10: 5137-5144, 2004. 13. Risbridger, G. P., Shibata, A., Ferguson , K. L., Stamey, T. A., McNeal, J. E., and Peehl, D...Christofori G, Pepper MS (2001) Vascular endothelial growth factor-C-mediated lymphangiogenesis promotes tumour metastasis. EMBO J 20: 672 – 682

  5. Optimal duration of androgen deprivation therapy following radiation therapy in intermediate- or high-risk non-metastatic prostate cancer: a systematic review and meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Leal, Frederico; Figueiredo, Maximiliano Augusto Novis de; Sasse, Andre Deeke, E-mail: sasse@cevon.com.br [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)

    2015-05-15

    Objectives: to investigate current evidence on the optimal duration of adjuvant hormone deprivation for prostate cancer treated with radiation therapy with curative intent. Materials and Methods: A systematic search was performed in electronic databases. Data from randomized trials comparing different durations of hormone blockade was collected for pooled analysis. Overall survival, disease-free survival, disease-specific survival and toxicity were the outcomes of interest. Meta-analyses were performed using random-effects model. Results: Six studies met the eligibility criteria. For overall survival, the pooled data from the studies demonstrated a statistically significant benefit for longer hormone deprivation (Hazard Ratio 0.84; 95% CI 0.74 - 0.96). A statistically significant benefit was also found for disease-free survival (Hazard Ratio 0.74; 95% CI 0.62 - 0.89), and disease-specific survival (Hazard Ratio 0.73; 95% CI 0.62 - 0.85). Studies with longer blockade duration arm demonstrated greater benefit. Toxicity was low, with no increase in cardiovascular events. Conclusions: Longer duration of androgen deprivation combined to radiotherapy prolongs OS, DFS and DSS in patients with intermediate and high-risk non-metastatic prostate cancer. However, this evidence is based on trials using older radiation techniques, and further research of combination of androgen deprivation and new RT technologies may be warranted. (author)

  6. The latest advances of experimental research on targeted gene therapy for prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Dongliang Pan; Lianchao Jin; Xianghua Zhang

    2013-01-01

    The absence of ef ective therapies for castration-resistant prostate cancer (CRPC) establishes the need to de-velop novel therapeutic modality, such as targeted gene therapy, which is ideal for the treatment of CRPC. But its application has been limited due to lack of favorable gene vector and the reduction of“bystander ef ect”. Consequently, scientists al over the world focus their main experimental research on the fol owing four aspects:targeted gene, vector, transfer means and comprehensive therapy. In this paper, we reviewed the latest advances of experimental research on targeted gene therapy for prostate cancer .

  7. Advances in molecular imaging of prostate cancer targeting prostate specific membrane antigen with small molecular radionuclide probes%以核素标记前列腺特异性膜抗原小分子抑制剂为探针的前列腺癌分子影像研究进展

    Institute of Scientific and Technical Information of China (English)

    胡四龙(综述); 许晓平; 章英剑(审校)

    2015-01-01

    Prostate speciifc membrane antigen (PSMA) is expressed in normal prostate epithelial cells and strongly up regulated in initial and advanced prostate carcinoma. Therefore, PSMA is an attractive molecular target for the detection of primary and metastatic lesions. It plays an important role in the diagnosis, staging, prognostic evaluation and targeted treatment in prostate carcinoma patients. This review will summarize the progress of small molecular radionuclide probes, which targeted PSMA, for visualizing prostate cancer.%前列腺特异性膜抗原(PSMA)高表达于前列腺癌及其转移灶中,可作为生物分子靶点,在前列腺癌的早期诊断、分期、复发检测、预后判断及靶向治疗中具有重要价值。本文重点综述以核素标记PSMA小分子抑制剂为探针的前列腺癌分子影像研究进展。

  8. Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer: part 2. Final evaluation of the Scandinavian Prostatic Cancer Group (SPCG) Study No. 5

    DEFF Research Database (Denmark)

    Hedlund, P.O.; Damber, J.E.; Hagerman, I.;

    2008-01-01

    To compare parenteral estrogen therapy in the form of high-dose polyestradiol phosphate (PEP; Estradurin) with combined androgen deprivation (CAD) in the treatment of prostate cancer patients with skeletal metastases. The aim of the study was to compare anticancer efficacy and adverse events...

  9. [Advances in highly conformal radiotherapy for prostate cancer: past, current, and future].

    Science.gov (United States)

    Ishikawa, Hitoshi; Hashimoto, Takayuki; Makishima, Hirokazu; Mizumoto, Masashi; Okumura, Toshiyuki; Sakurai, Hideyuki

    2012-01-01

    Recent advance in the field of radiation oncology, especially in medical physics for radiation therapy (RT), has considerably improved treatment outcomes of various cancers including prostate cancer with regard to both of tumor control and morbidity. Three-dimensionally conformal RT with image-guided radiotherapeutic modalities for accurate tumor localization, such as brachytherapy, intensity-modulated radiation therapy (IMRT), and charged particle beam RT can thereby deliver a large dose to the tumor and allow the sparing of surrounding normal tissues. It is thought that prostate cancer is one of representative cancers which have been treated with RT as a curative intent and benefited from novel conformal RT techniques. Because the number of prostate cancer patients has been increasing year by year in Japan as results from wide spread of PSA screening and rapid change in life style, RT has been recently playing much more important roles in the curative treatment for patients with prostate cancer. Hence, we will review the outcomes of RT for prostate cancer and introduce the benefit of modern RT modalities from clinical aspect. In addition, our future prospect to further yield better disease control with minimum morbidity compared with present RT will be also mentioned in the report.

  10. Prostate specific membrane antigen- a target for imaging and therapy with radionuclides

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Choyke, Peter L; Capala, Jacek

    2010-01-01

    Prostate cancer continues to represent a major health problem, and yet there is no effective treatment available for advanced metastatic disease. Thus, there is an urgent need for the development of more effective treatment modalities that could improve the outcome. Because prostate specific...... membrane antigen (PSMA), a transmembrane protein, is expressed by virtually all prostate cancers, and its expression is further increased in poorly differentiated, metastatic, and hormone-refractory carcinomas, it is a very attractive target. Molecules targeting PSMA can be labelled with radionuclides...... to become both diagnostic and/or therapeutic agents. The use of PSMA binding agents, labelled with diagnostic and therapeutic radio-isotopes, opens up the potential for a new era of personalized management of metastatic prostate cancer....

  11. Recent advances in the surgical treatment of benign prostatic hyperplasia

    Science.gov (United States)

    Rocco, Bernardo; Ferreira, Rafael Coelho; Spinelli, Matteo; Cozzi, Gabriele; Dell’Orto, Paolo; Patel, Vipul; Rocco, Francesco

    2011-01-01

    TURP for many years has been considered the gold standard for surgical treatment of BPH. Symptoms relief, improvement in Maximum flow rate and reduction of post void residual urine have been reported in several experiences. Notwithstanding a satisfactory efficacy, concerns have been reported in terms of safety outcomes:intracapsular perforation, TUR syndrome, bleeding with a higher risk of transfusion particularly in larger prostates have been extensivelyreported in the literature. In the recent years the use of new forms of energy and devices suchas bipolar resector, Ho: YAG and potassium-titanyl-phosphate laserare challenging the role of traditional TURP for BPH surgical treatment. In 1999 TURP represented the 81% of surgical treatment for BPHversus 39% of 2005. Is this a marketing driven change or is there areal advantage in new technologies? We analyzed guidelines and higher evidence studies to evaluate therole of the most relevant new surgical approaches compared to TURPfor the treatment of BPH. In case of prostates of very large size the challenge is ongoing, withminimally invasive laparoscopic approach and most recently roboticapproach. We will evaluate the most recent literature on thisemerging field. PMID:22164196

  12. Two Domains of Vimentin Are Expressed on the Surface of Lymph Node, Bone and Brain Metastatic Prostate Cancer Lines along with the Putative Stem Cell Marker Proteins CD44 and CD133

    Energy Technology Data Exchange (ETDEWEB)

    Steinmetz, Nicole F. [Case Western Reserve University, Department of Biomedical Engineering, 10900 Euclid Ave, Cleveland, OH 44106 (United States); Maurer, Jochen [Sanford-Burnham, Medical Research Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037 (United States); Sheng, Huiming [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States); Bensussan, Armand [INSERM U976, Hôpital Saint Louis, F-75475 Paris (France); Department of Immunology, Dermatology and Oncology, Univ Paris Diderot, Sorbonne Paris Cité, UMRS976 F-75475 Paris (France); Maricic, Igor; Kumar, Vipin [Torrey Pines Institute for Molecular Studies, Laboratory of Autoimmunity, 3550 General Atomics Court, San Diego, CA 92121 (United States); Braciak, Todd A., E-mail: tbraciak@tpims.org [Torrey Pines Institute for Molecular Studies, Division of Immune Regulation, 3550 General Atomics Court, San Diego, CA 92121 (United States)

    2011-07-13

    Vimentin was originally identified as an intermediate filament protein present only as an intracellular component in many cell types. However, this protein has now been detected on the surface of a number of different cancer cell types in a punctate distribution pattern. Increased vimentin expression has been indicated as an important step in epithelial-mesenchymal transition (EMT) required for the metastasis of prostate cancer. Here, using two vimentin-specific monoclonal antibodies (SC5 and V9 directed against the coil one rod domain and the C-terminus of the vimentin protein, respectively), we examined whether either of these domains would be displayed on the surface of three commonly studied prostate cancer cell lines isolated from different sites of metastases. Confocal analysis of LNCaP, PC3 and DU145 prostate cancer cell lines (derived from lymph node, bone or brain prostate metastases, respectively) demonstrated that both domains of vimentin are present on the surface of these metastatic cancer cell types. In addition, flow cytometric analysis revealed that vimentin expression was readily detected along with CD44 expression but only a small subpopulation of prostate cancer cells expressed vimentin and the putative stem cell marker CD133 along with CD44. Finally, Cowpea mosaic virus (CPMV) nanoparticles that target vimentin could bind and internalize into tested prostate cancer cell lines. These results demonstrate that at least two domains of vimentin are present on the surface of metastatic prostate cancer cells and suggest that vimentin could provide a useful target for nanoparticle- or antibody- cancer therapeutic agents directed against highly invasive cancer and/or stem cells.

  13. Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans With Bone-Metastatic Prostate Cancer

    Science.gov (United States)

    2014-09-01

    al. (1988) The combined effects of dietary protein and fat intake during the promotion phase of 7,12-dimethylbenz(a)anthracene-induced breast cancer...Belanger B, Belanger A, Labrie F, et al. Comparison of residual C-19 steroids in plasma and prostatic tissue of human, rat and guinea pig after

  14. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma.

    Science.gov (United States)

    Axelson, Michael; Liu, Ke; Jiang, Xiaoping; He, Kun; Wang, Jian; Zhao, Hong; Kufrin, Dubravka; Palmby, Todd; Dong, Zedong; Russell, Anne Marie; Miksinski, Sarah; Keegan, Patricia; Pazdur, Richard

    2013-05-01

    The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international trial of vismodegib, administered orally at 150 mg daily until disease progression, in patients with pathologically confirmed, recurrent, locally advanced basal cell carcinoma (laBCC) or metastatic basal cell carcinoma (mBCC). An independent review committee confirmed an overall response rate (ORR) of 30.3% [95% confidence interval (CI): 15.6-48.2] in 33 patients with mBCC and an ORR of 42.9% (95% CI: 30.5-56.0) in 63 patients with laBCC; median response durations were 7.6 months and 7.6 months for patients with mBCC and laBCC, respectively. The most common adverse reactions were muscle spasms, alopecia, dysgeusia, weight loss, fatigue, nausea, diarrhea, decreased appetite, constipation, cough, arthralgias, vomiting, headache, ageusia, insomnia, and upper respiratory tract infection. Animal toxicology studies confirmed that vismodegib is a potent teratogenic agent. Approval was based on durable objective tumor responses supported by knowledge of the pathologic role of Hedgehog signaling in BCC and acceptable toxicity in a population without effective alternative therapies.

  15. Metastasis of Prostate Adenocarcinoma to the Testis

    Science.gov (United States)

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  16. Efficacy and safety of enzalutamide in patients 75 years or older with chemotherapy-naive metastatic castration-resistant prostate cancer

    DEFF Research Database (Denmark)

    Graff, J N; Baciarello, G; Armstrong, A J;

    2016-01-01

    for an overall higher incidence of falls among elderly patients than younger patients [84/609 (13.8%) versus 62/1106 (5.6%)] and among elderly patients receiving enzalutamide than those receiving placebo [61/317 (19.2%) versus 23/292 (7.9%)]. CONCLUSIONS: Elderly men benefited from treatment with enzalutamide...... in terms of OS and rPFS. Enzalutamide was well tolerated in the elderly subgroup and those aged falls. CLINICAL TRIAL IDENTIFIER: NCT01212991, ClinicalTrials.gov.......BACKGROUND: Prostate cancer disproportionately affects older men. Because age affects treatment decisions, it is important to understand the efficacy and tolerability of therapies for advanced prostate cancer in elderly men. This analysis describes efficacy and safety outcomes in men aged ≥75 years...

  17. Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer.

    Science.gov (United States)

    Dang, Thu Oanh; Ogunniyi, Adebayo; Barbee, Meagan S; Drilon, Alexander

    2016-01-01

    The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.

  18. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

    Science.gov (United States)

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

    2016-02-29

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  19. Randomized phase III study comparing paclitaxel/cisplatin/gemcitabine and gemcitabine/cisplatin in patients with locally advanced or metastatic urothelial cancer without prior systemic therapy

    DEFF Research Database (Denmark)

    Bellmunt, Joaquim; von der Maase, Hans; Mead, Graham M;

    2012-01-01

    The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival.......The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival....

  20. Recent advances in treatment for Benign Prostatic Hyperplasia [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Simon van Rij

    2015-12-01

    Full Text Available Clinical benign prostatic hyperplasia (BPH, often identified as a worsening ability of a male to pass urine, is a significant problem for men in our society. In 2015, the use of personalised medicine is tailoring treatment to individual patient needs and to genetic characteristics. Technological advances in surgical treatment are changing the way BPH is treated and are resulting in less morbidity. The future of BPH treatments is exciting, and a number of novel techniques are currently under clinical trial.

  1. Exoftalmo unilateral por metástase orbitária de carcinoma de próstata Unilateral exophthalmos secondary to orbital metastatic carcinoma of the prostate: a case report

    Directory of Open Access Journals (Sweden)

    José Carlos Corrêa Barbosa

    1972-06-01

    Full Text Available É relatado um caso de exoftalmo ou proptose unilateral direita, causado por metástase orbitária de carcinoma da próstata em paciente negro, na 6.ª década de vida, com evolução de 9 meses. O exame neuro-ocular revelou acentuada diminuição da agudeza visual, perturbação para visão de cores, perda da convergência, diminuição dos reflexos à luz e acomodação e restrição dos movimentos oculares. O paciente apresentava discreta disbasia esquerda por metástase no fêmur. Exames laboratoriais, radiológicos e a biópsia confirmaram a etiologia carcinomatosa da manifestação ocular.A case of right unilateral exophthalmos secondary to metastatic carcinoma of the prostate, in a 68 years old negro patient in which the ocular manifestation lasted 9 months is reported The extrinsic movements of the eye were limited. Pupils reacted slightly to light and accommodation. There was no ocular convergence. The vision of the right eye was blurred and there was mild color vision. The prostate was found to be petrous by touch specially in the right portion. The laboratory findings pointed to a prostatic carcinoma. Bone X-rays were strongly suggestive of metastatic tumour. The histological examination of the orbital tumour showed prostatic tumour cells.

  2. Prostate cancer progression attributed to autonomic nerve development: Potential for therapeutic prevention of localized and metastatic disease

    OpenAIRE

    2013-01-01

    In a study recently published in Science, Magnon et al. show that both the sympathetic and parasympathetic components of the autonomic nervous system play an integral part in the development and dissemination of prostate cancer (PCa). Inhibition of the sympathetic nervous system (SNS) and disruption of the adrenergic receptors, specifically Ardβ2, resulted in the prevention of primary PCa tumor development in mice. The authors found that inhibition of the SNS is only successful in preventing ...

  3. Adipose Stem Cell-Based Therapeutic Targeting of Residual Androgens in African Americans with Bone-Metastatic Prostate Cancer

    Science.gov (United States)

    2015-11-01

    in vitro and in vivo; (b) determine if α- HSD-expressing osteotropic ASCCont will nullify the ADMSCAA- mediated CaP cell growth and metastasis in vitro...capable of mediating continued androgen-receptor (AR) signaling and gene expression [27]. Moreover, residual intra-prostatic androgens are implicated in...nearly every mechanism whereby AR- mediated signaling leads to the development of castration-resistant disease [28]. The increased expression of

  4. High-Throughput Sequencing of Germline and Tumor From Men with Early-Onset Metastatic Prostate Cancer

    Science.gov (United States)

    2015-10-01

    molecularly profile both the initial prostate cancer (PR-259) and the liver biopsy which contained histologically-confirmed small cell/neuroendocrine...Therefore, we modified our approach to use archived FFPE biopsy and prostatectomy tumor specimen and to analyze these specimens using a qPCR...number alterations are indicated. 4 with small cell carcinoma of the liver and eventually succumbed from this disease approximately one year from

  5. A transient increase in eosinophils is associated with prolonged survival in men with metastatic castration-resistant prostate cancer who receive sipuleucel-T.

    Science.gov (United States)

    McNeel, Douglas G; Gardner, Thomas A; Higano, Celestia S; Kantoff, Philip W; Small, Eric J; Wener, Mark H; Sims, Robert B; DeVries, Todd; Sheikh, Nadeem A; Dreicer, Robert

    2014-10-01

    Sipuleucel-T is an autologous cellular immunotherapy used to treat asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). Traditional short-term indicators of clinical response commonly used with chemotherapy have not correlated with survival in patients treated with sipuleucel-T. This retrospective study aimed to evaluate laboratory parameters as possible early biomarkers associated with clinical benefit following sipuleucel-T treatment. Patients treated with sipuleucel-T from three randomized, controlled, phase III clinical trials in mCRPC were considered: IMPACT (NCT00065442; n = 512), D9901 (NCT00005947; n = 127), and D9902A (NCT01133704; n = 98). Patients from these trials were included in this study if their samples were analyzed by the central laboratory and if data were available from baseline and ≥ 1 posttreatment time point (n = 377). We found that sipuleucel-T treatment was associated with a transient increase in serum eosinophil count at week 6 that resolved by week 14 in 28% of patients (105 of 377). This eosinophil increase correlated with induced immune response, longer prostate cancer-specific survival [HR, 0.713; 95% confidence interval (CI), 0.525-0.970; P = 0.031], and a trend in overall survival (HR, 0.753; 95% CI, 0.563-1.008; P = 0.057). Median serum globulin protein levels also increased transiently, which was associated with antigen-specific antibody responses; however, this finding did not correlate with longer survival. We conclude that transient increases in eosinophils at week 6 may be a useful, objective, short-term indicator of global immune activation and survival benefit with sipuleucel-T in patients with mCRPC. This observation warrants prospective evaluation in future clinical trials.

  6. Definition of molecular determinants of prostate cancer cell bone extravasation.

    Science.gov (United States)

    Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J

    2013-01-15

    Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

  7. Association of Type 2 Diabetes Susceptibility Variants With Advanced Prostate Cancer Risk in the Breast and Prostate Cancer Cohort Consortium

    Science.gov (United States)

    Machiela, Mitchell J.; Lindström, Sara; Allen, Naomi E.; Haiman, Christopher A.; Albanes, Demetrius; Barricarte, Aurelio; Berndt, Sonja I.; Bueno-de-Mesquita, H. Bas; Chanock, Stephen; Gaziano, J. Michael; Gapstur, Susan M.; Giovannucci, Edward; Henderson, Brian E.; Jacobs, Eric J.; Kolonel, Laurence N.; Krogh, Vittorio; Ma, Jing; Stampfer, Meir J.; Stevens, Victoria L.; Stram, Daniel O.; Tjønneland, Anne; Travis, Ruth; Willett, Walter C.; Hunter, David J.; Le Marchand, Loic; Kraft, Peter

    2012-01-01

    Observational studies have found an inverse association between type 2 diabetes (T2D) and prostate cancer (PCa), and genome-wide association studies have found common variants near 3 loci associated with both diseases. The authors examined whether a genetic background that favors T2D is associated with risk of advanced PCa. Data from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium, a genome-wide association study of 2,782 advanced PCa cases and 4,458 controls, were used to evaluate whether individual single nucleotide polymorphisms or aggregations of these 36 T2D susceptibility loci are associated with PCa. Ten T2D markers near 9 loci (NOTCH2, ADCY5, JAZF1, CDKN2A/B, TCF7L2, KCNQ1, MTNR1B, FTO, and HNF1B) were nominally associated with PCa (P < 0.05); the association for single nucleotide polymorphism rs757210 at the HNF1B locus was significant when multiple comparisons were accounted for (adjusted P = 0.001). Genetic risk scores weighted by the T2D log odds ratio and multilocus kernel tests also indicated a significant relation between T2D variants and PCa risk. A mediation analysis of 9,065 PCa cases and 9,526 controls failed to produce evidence that diabetes mediates the association of the HNF1B locus with PCa risk. These data suggest a shared genetic component between T2D and PCa and add to the evidence for an interrelation between these diseases. PMID:23193118

  8. Talazoparib in Treating Patients With Advanced or Metastatic Solid Tumors That Cannot Be Removed by Surgery and Liver or Kidney Dysfunction

    Science.gov (United States)

    2016-10-05

    Estrogen Receptor Negative; Head and Neck Squamous Cell Carcinoma; HER2/Neu Negative; Hormone-Resistant Prostate Cancer; Metastatic Pancreatic Adenocarcinoma; Progesterone Receptor Negative; Solid Neoplasm; Stage III Mesothelioma; Stage IIIA Gastric Cancer; Stage IIIA Non-Small Cell Lung Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Small Cell Lung Carcinoma; Stage IIIB Gastric Cancer; Stage IIIB Non-Small Cell Lung Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Small Cell Lung Carcinoma; Stage IIIC Gastric Cancer; Stage IIIC Ovarian Cancer; Stage IV Mesothelioma; Stage IV Non-Small Cell Lung Cancer; Stage IV Ovarian Cancer; Stage IV Small Cell Lung Carcinoma; Triple-Negative Breast Carcinoma

  9. Preclinical evaluation of intraoperative low-energy photon radiotherapy using sphericalapplicators in locally advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    François eBuge

    2015-09-01

    Full Text Available Background: Surgery plus adjuvant radiotherapy is standard care for locally advanced prostatecancer (stage pT3R1. Intraoperative low-energy photon radiotherapy offers several advantages overexternal beam radiotherapy, and several systems are now available for its delivery, using sphericalapplicators which require only limited shielding. The aim of this study was to evaluate the feasibilityof this technique for the prostate bed.Materials & Methods: Applicators were assessed using MRI image data and cadavericdissection. In cadavers, targeted tissues, defined as a urethral section, both neurovascular bundlesections, the bladder neck and the beds of the seminal vesicles, were marked with metallic surgicalclips. Distances between clips and applicator were measured using CT. A dosimetric study of theapplication of 12 Gy at 5mm depth was performed using CT images of prostatectomized cadavers.Results: Using MRI images from 34 prostate cancer patients, we showed that the ideal applicatordiameter ranges from 45 to 70 mm. Using applicators of different sizes to encompass the prostate bedin nine cadavers, we showed that the distance between target tissues and applicator was less than 2mm for all target tissues except the upper extremity of the seminal vesicles (19 mm. Dosimetric studyshowed a good dose distribution in all target tissues in contact with the applicator, with a lowprobability of rectum and bladder complication.Conclusions: Intraoperative radiotherapy of the prostate bed is feasible, with good coverage oftargeted tissues. Clinical study of safety and efficacy is now required.

  10. Chemotherapy and its evolving role in the management of advanced prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Michael T Schweizer; Emmanuel S Antonarakis

    2014-01-01

    prostate cancer has been recognized as being responsive to androgen deprivation since the 1940s when Charles Huggins ifrst described the role of surgical castration in managing these patients. However, androgen deprivation only results in transient disease control for the vast majority of men, with those progressing in spite of castrate testosterone levels labeled as having castrate-resistant prostate cancer (CRPC). Until 2004, the therapeutic arena for these patients had remained stagnant, with no agent having shown a survival gain in the CRPC setting. Two landmark publications changed the prostate cancer treatment landscape by providing‘level-1 evidence’ that docetaxel-based chemotherapy led to prolongation in overall survival (OS). This was followed by the approval of cabazitaxel in 2010 on the basis of Phase III data demonstrating its efifcacy in patients pretreated with docetaxel. More recently, a number of next-generation androgen-directed agents (e.g. abiraterone and enzalutamide) have also been shown to lead to a survival beneift in men with CRPC. With so many new treatment options available, a number of questions remain. These include:how to best sequence chemotherapy with these newer hormonal agents, the clinical implication of cross-resistance between taxanes and androgen-directed agents and which subsets of patients may beneift most from early use of chemotherapy. This review will provide an overview of the evolving role of chemotherapy in the management of advanced prostate cancer in the current era.

  11. Updates in advanced diffusion-weighted magnetic resonance imaging techniques in the evaluation of prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Hebert; Alberto; Vargas; Edward; Malnor; Lawrence; Yousef; Mazaheri; Evis; Sala

    2015-01-01

    Diffusion-weighted magnetic resonance imaging(DWMRI) is considered part of the standard imaging protocol for the evaluation of patients with prostate cancer.It has been proven valuable as a functional tool for qualitative and quantitative analysis of prostate cancer beyond anatomical MRI sequences such as T2-weighted imaging. This review discusses ongoing controversies in DW-MRI acquisition, including the optimal number of b-values to be used for prostate DWI, and summarizes the current literature on the use of advanced DWMRI techniques. These include intravoxel incoherent motion imaging, which better accounts for the nonmono-exponential behavior of the apparent diffusion coefficient as a function of b-value and the influence of perfusion at low b-values. Another technique is diffusion kurtosis imaging(DKI). Metrics from DKI reflect excess kurtosis of tissues, representing its deviation from Gaussian diffusion behavior. Preliminary results suggest that DKI findings may have more value than findings from conventional DW-MRI for the assessment of prostate cancer.

  12. A comparison of androgen deprivation therapy versus surgical castration for patients with advanced prostatic carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yu-hsiang LIN; Chien-lun CHEN; Chen-pang HOU; Phei-lang CHANG; Ke-hung TSUI

    2011-01-01

    Airn:To examine the outcomes of patients with advanced prostate carcinoma who underwent medical or surgical castration.Methods:A hundred twenty one consecutive cases of patients with advanced prostate carcinoma who underwent medicaI or surgical castration between 2001 and 2006 were retrospectively reviewed.Associations between clinicaI outcomes and prognostic scoring factors were determined based on the Reijke study.In the surgical and medical castration groups.the impact on the prostate-specific antigen(PSA)normalization rate,the rebound rate and the disease-free survivaI rate were evaluated.The mean foIlow-up was 36.1months.Results:In the initial 12 months.there were no statisticaI differences in the PSA normalization rate and the PSA rebound rate between the two groups.However,the PSA rebound rate after the 12th month(20.90%vs 40.74%.P=-0.0175)and the 18th month PSA normalization rate(59.70%vs 37.04%.P=0.0217)differed significantly between the two groups,and these differences were maintained to the end of the study.When comparing patients grouped according to Reijke prognosis scores.there was no difference between medical and surgical castration for the good prognosis group.However, among the patients given a poor prognosis,surgical castration was superior in terms of the PSA normalization rate,the PSA rebound rate.the tumor progression-free survival rate(P<0.001)and the overalI survivaI rate (P<0.001).Conclusion:Advanced prostate carcinoma patients with poor pretreatment prognosis scores should undergo surgical castration rather than medical castration for better PSA rebound rates and overaII survival.

  13. Changes in skeletal tumor activity on {sup 18}F-choline PET/CT in patients receiving {sup 223}radium radionuclide therapy for metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Miyazaki, Kyle S. [Oncology Research Dept. and Hamamatsu/Queen' s PET Imaging Center, The Queen' s Medical Center, Honolulu (United States); Kang, Yu; Kwee, Sandi A. [Dept. of Medical Physics, School of Allied Health Sciences, University of Nevada Las Vegas, Las Vegas (United States)

    2015-06-15

    Radium-223 dichloride is an alpha-emitting radiopharmaceutical shown to prolong survival in patients with castrate-resistant prostate cancer (CRPC) and symptomatic skeletal metastases. This report describes in two patients the acute changes in bone metastatic activity detected by F-18 choline PET/CT imaging midway during treatment with radium-223 dichloride. In addition to visual and standardized uptake value analysis, changes in the whole-body tumor burden were quantified by measuring the difference in net metabolically active tumor volume (MATV) and total lesion activity (TLA) between pre- and mid-treatment PET scans. After the third dose of radium-223 dichloride, near-total disappearance of abnormal skeletal activity was observed in one case (net MATV change from 260.7 to 0.8 cc; net TLA change from 510.7 to 2.1), while a heterogeneous tumor response was observed in the other (net MATV change from 272.2 to 241.3 cc; net TLA change from 987.1 to 779.4). Corresponding normalization and persistent elevation in serum alkaline phosphatase levels were observed in these cases, respectively. Further research is needed to determine the predictive value of serial F-18 choline PET/CT imaging in patients receiving radium-223 dichloride for CRPC.

  14. Devising and external validation of a prognostic classification of metastatic involvement risk to pelvic lymph nodes in patients with newly diagnosed prostate cancer

    Directory of Open Access Journals (Sweden)

    E. A. Leusik

    2015-01-01

    Full Text Available Objective – assessing the predictive significance of clinical, histologic and biochemical factors for prediction of metastases in pelvic lymph nodes (MPLN, devising and validating of prognostic classification.Materials and methods. The study enrolled 1140 patients subjected to radical prostatectomy (RPE with standard pelvic lymphadenectomy for prostate adenocarcinoma: 865 of them at the classification devising stage and 275 in the course of validation.Results. According to the findings of multivariate logistic regression analysis, PSA level, the tumor cT stage and Gleason score are independent predictors of MPLN detection after RPE (p < 0.05. The prognostic factors were stratified by score for assessing the detection of regional metastases after RPE, depending on the combination of predictors. In the group of patients with a score estimate of prognostic factors < 10, the MPLN detection rate was significantly lower than in the group of with a score estimate > 15, accounting for 3.5 % and 23.7 % respectively (р < 0.0001. In the course of validating the obtained findings in clinic, metastatic involvement of pelvic lymph nodes found in the result of RPE was diagnosed in 40.0 % of the patients with a score estimate > 15 and only in 1.3 % of those with a total estimate of prognostic factors < 10 (р < 0.0001.

  15. Immunotherapy with Sipuleucel-T (APC8015 in patients with metastatic castration-refractory prostate cancer (mCRPC: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Tobias Engel Ayer Botrel

    2012-12-01

    Full Text Available Objective To perform a systematic review and meta-analysis of all randomized controlled trials comparing the efficacy of Sipuleucel-T versus placebo for asymptomatic or minimally symptomatic metastatic castration-refractory prostate cancer (mCRPC. Materials ans Methods Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The endpoints were overall survival (OS, time to progression (TTP and side effects. We performed a meta-analysis (MA of the published data. The results are expressed as Hazard Ratio (HR or Risk Ratio (RR, with their corresponding 95% confidence intervals (CI 95%. Results The final analysis included 3 trials comprising 737 patients. The TTP was similar in patients who received Sipuleucel-T or placebo (fixed effect: HR = 0.89; CI 95% = 0.75 to 1.05; p = 0.16, with no heterogeneity detected on this analysis (Chi2 = 2.14, df = 2 (P = 0.34; I2 = 6%. The results showed a higher overall survival in patients treated with Sipuleucel-T (fixed effect: HR = 0.74; CI 95% = 0.61 to 0.89; p = 0.001; NNT = 3. We found no heterogeneity on this analysis either (Chi2 = 1.46, df = 2 (P = 0.48; I2 = 0%. The incidence of adverse events (grade > 3 was the same in both groups. Conclusion Sipuleucel-T prolongs overall survival in patients with asymptomatic or minimally symptomatic mCRPC.

  16. The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone

    Science.gov (United States)

    Boegemann, Martin; Schlack, Katrin; Thomes, Stefan; Steinestel, Julie; Rahbar, Kambiz; Semjonow, Axel; Schrader, Andres Jan; Aringer, Martin; Krabbe, Laura-Maria

    2017-01-01

    The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR) and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS) and overall survival (OS) was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR 5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months) (HR: 1.6 (95%CI:0.9–2.8); p = 0.11). After multivariate adjustment (MVA), ECOG > 0–1, baseline LDH>upper limit of normal (UNL) and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months) (HR: 2.3 (95%CI:1.3–4.0); p 0–1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to 5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully. PMID:28208664

  17. Phase I clinical trial of sipuleucel-T combined with escalating doses of ipilimumab in progressive metastatic castrate-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Scholz M

    2017-03-01

    Full Text Available Mark Scholz,1 Sabrina Yep,1 Micah Chancey,1 Colleen Kelly,1 Ken Chau,1 Jeffrey Turner,1 Richard Lam,1 Charles G Drake,2,3 1Prostate Oncology Specialists, Inc., Marina del Rey, CA, 2The Sidney Kimmel Cancer Center, 3The James Buchanan Brady Urological Institute, John Hopkins Medical Institutions, Baltimore, MD, USA Background: Sipuleucel-T (SIP-T, which functions by stimulating cancer-specific dendritic cells, prolongs survival in men with prostate cancer. Ipilimumab (IPI achieved a borderline survival advantage in a large randomized trial. SIP-T and IPI are potentially synergistic. Patients and Methods: Nine men with progressive metastatic castrate-resistant prostate cancer (mCRPC were treated prospectively with SIP-T followed immediately by IPI with one of the following doses of IPI: 1 mg/kg at 1 week after SIP-T; 1 mg/kg at 1 and 4 weeks after SIP-T; or 1 mg/kg at 1, 4, and 7 weeks after SIP-T. Three patients were evaluated at each level. Cancer-specific immunoglobulins directed at granulocyte-macrophage-colony-stimulating factor/prostatic acid phosphatase (PAP fusion protein (PA2024 and PAP were measured prior to SIP-T, after SIP-T, 1 week after IPI, every other month for 5 months, then every 3 months for an additional 12 months. Results: Adverse events of SIP-T were consistent with previous reports. IPI only caused a transient grade 1 rash in one patient. Median age, Gleason score, and number of previous hormonal interventions were 77 years, 8, and 3, respectively. Eight men had bone metastases and one had lymph node metastasis. Statistically significant increases in serum immunoglobulin G (IgG and IgG-IgM specific for PA2024 and PAP occurred after SIP-T. An additional statistically significant increase in the aforementioned immunoglobulins – above the levels achieved by SIP-T – occurred after IPI. Median clinical follow-up was 36 months (range: 26–40. Three patients died from progressive disease after 9, 18, and 20 months. Out of the

  18. What is the correct staging and treatment strategy for locally advanced prostate cancer extending to the bladder?

    Directory of Open Access Journals (Sweden)

    Özgür Haki Yüksel

    2015-07-01

    Full Text Available In locally advanced prostate cancer with bladder invasion, frequently encountered problems such as bleeding, urinary retention, hydronephrosis, and pain create distress for the patients. Therefore patients’ quality of life is disrupted and duration of hospitalization is prolonged. Relevant literature about accurate staging and treatment of locally advanced prostate cancer with bladder invasion was investigated. Locally advanced prostate cancer can present as a large-volume aggressive tumor extending beyond boundaries of prostate gland, and involving neighboring structures which can be involved as recurrence(s following initial local therapy. Survival times of these patients can range between 5 and 8 years. Their common characteristics are adverse and severe local symptoms unfavorably affecting quality of life Control of local symptoms and their effective palliation are independent clinical targets influencing survival outcomes of these patients. The treatment outcomes of locally advanced prostate cancer into the bladder are currently debatable. Although in the current TNM classification, it is defined in T4a, we think that this may be categorized as a subgroup of T3 and thus encourage surgeons for the indication of radical surgeries (radical prostatectomy, radical cystoprostatectomy in selected patient populations after discussing issues concerning consequences of the treatment alternatives, and expectations with the patients. Cystoprostatectomy followed by immediate androgen deprivation therapy may be a feasible option for selected patients with previously untreated prostate cancer involving the bladder neck because of excellent local control and long term survival.

  19. Long-term survival results of a randomized trial comparing gemcitabine/cisplatin and methotrexate/vinblastine/doxorubicin/cisplatin in patients with locally advanced and metastatic bladder cancer

    DEFF Research Database (Denmark)

    Roberts, J. T.; Maase, Hans von der; Sengeløv, Lisa

    2006-01-01

    Purpose: To compare long-term survival in patients with locally advanced       and metastatic transitional cell carcinoma (TCC) of the urothelium treated       with gemcitabine plus cisplatin (GC) or       methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). PATIENTS AND       METHODS: Efficacy...

  20. A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma : The TRUSTS trial

    NARCIS (Netherlands)

    Bui-Nguyen, B.; Butrynski, J. E.; Penel, N.; Blay, J. Y.; Isambert, N.; Milhem, M.; Kerst, J. M.; Reyners, A. K. L.; Litiere, S.; Marreaud, S.; Collin, F.; van der Graaf, W. T. A.

    2015-01-01

    Purpose: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour infusion

  1. A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial

    NARCIS (Netherlands)

    Bui-Nguyen, B.; Butrynski, J.E.; Penel, N.; Blay, J.Y.; Isambert, N.; Milhem, M.; Kerst, J.M.; Reyners, A.K.; Litiere, S.; Marreaud, S.; Collin, F.; Graaf, W.T.A. van der

    2015-01-01

    PURPOSE: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour infusion

  2. Sipuleucel-T for the Treatment of Metastatic Hormone-Relapsed Prostate Cancer: A NICE Single Technology Appraisal; An Evidence Review Group Perspective.

    Science.gov (United States)

    Simpson, Emma L; Davis, Sarah; Thokala, Praveen; Breeze, Penny R; Bryden, Peter; Wong, Ruth

    2015-11-01

    The National Institute for Health and Care Excellence (NICE) invited Dendreon, the company manufacturing sipuleucel-T, to submit evidence for the clinical and cost effectiveness of sipuleucel-T for asymptomatic or minimally symptomatic, metastatic, non-visceral hormone-relapsed prostate cancer patients in whom chemotherapy is not yet clinically indicated, as part of NICE's single technology appraisal process. The comparator was abiraterone acetate (AA) or best supportive care (BSC). The School of Health and Related Research at the University of Sheffield was commissioned to act as the Evidence Review Group (ERG). This paper describes the company submission (CS), ERG review, and subsequent decision of the NICE Appraisal Committee (AC). The ERG produced a critical review of the clinical and cost-effectiveness evidence of sipuleucel-T based upon the CS. Clinical-effectiveness data relevant to the decision problem were taken from three randomised controlled trials (RCTs) of sipuleucel-T and a placebo (PBO) comparator of antigen-presenting cells (APC) being re-infused (APC-PBO) (D9901, D9902A and D9902B), and one RCT (COU-AA-302) of AA plus prednisone vs. PBO plus prednisone. Two trials reported a significant advantage for sipuleucel-T in median overall survival compared with APC-PBO: for trial D9901, an adjusted hazard ratio (HR) 0.47; (95 % confidence interval [CI] 0.29, 0.76) p Sipuleucel-T and APC-PBO groups did not differ significantly in time to disease progression, in any of the three RCTs. Most adverse events developed within 1 day of the infusion, and resolved within 2 days. The CS included an indirect comparison of sipuleucel-T (D9902B) and AA plus prednisone (COU-AA-302). As trials differed in prior use of chemotherapy, an analysis of only chemotherapy-naïve patients was included, in which the overall survival for sipuleucel-T and AA was not significantly different, HR 0.94 (95 % CI 0.69, 1.28) p = 0.699. The ERG had several concerns regarding the data and

  3. Vaccine Treatment for Prostate Cancer

    Science.gov (United States)

    ... Back After Treatment Prostate Cancer Treating Prostate Cancer Vaccine Treatment for Prostate Cancer Sipuleucel-T (Provenge) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  4. Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program

    DEFF Research Database (Denmark)

    See, William A; Wirth, Manfred P; McLeod, David G;

    2002-01-01

    We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer.......We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer....

  5. Bioengineering Multifunctional Quantum Dot-Polypeptide Assemblies and Immunoconjugates for the Ablation of Advanced Prostate Cancer Disease

    Science.gov (United States)

    2008-02-01

    urgency for the discovery of site-specific therapeutics for residual disease and metastasis in advanced prostate cancer. PROSTATE-SPECIFIC MEMBRANE...Chromek, M., et al., The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection. Nat. Med., 2006. 12(6): p. 636...cathelicidin protects the urinary tract against invasive bacterial infection. Nat Med 2006;12:636–41. 22. Berezin V, Bock E. NCAM mimetic peptides: Phar

  6. Prostate Cancer Foundation

    Science.gov (United States)

    ... P 2 rovocative Questions PCCTC Scientific Retreat Coffey-Holden Research News Faces of Prostate Cancer [4] Survivors ... Foundation News The Prostate Cancer Foundation’s 2016 Coffey-Holden Prostate Cancer Academy Meeting accelerates advances in the ...

  7. Prostatic melanosis

    Directory of Open Access Journals (Sweden)

    Kemal DENİZ

    2007-09-01

    Full Text Available Prostatic melanosis is a rare lesion that is characterized by melanin-containing spindle cells mainly located in the stroma of the prostate gland. This lesion is certainly benign and not a precursor of malignant melanoma. However, differential diagnosis of melanosis with primary and metastatic malignant melanoma is extremely important because of the different biological nature and clinical behavior of these two entities. Recognition of the spectrum of pigmented lesions in the prostate gland is essential to take into consideration of the diagnosis of melanocytic lesions.In this paper, a case of melanosis

  8. What is the role of sipuleucel-T in the treatment of patients with advanced prostate cancer? An update on the evidence.

    Science.gov (United States)

    Hu, Rachel; George, Daniel J; Zhang, Tian

    2016-08-01

    Prostate cancer is the most common cancer in men and the second most deadly. About one-third of patients with prostate cancer will develop metastatic disease. We discuss the six United States Food and Drug Administration (FDA) approved treatments for metastatic castrate-resistant prostate cancer (mCRPC) with a strong focus on sipuleucel-T. Sipuleucel-T is the first immunotherapy shown to improve survival in asymptomatic or minimally-symptomatic mCRPC. Herein, we discuss the proposed mechanism of sipuleucel-T and its synthesis. We describe in detail the three randomized controlled trials (RTCs) that led to its approval. We also compiled the newest research regarding use of sipuleucel-T with other agents and in different patient populations. Finally, we discuss the current ongoing trials.

  9. Tolerability of Therapies Recommended for the Treatment of Hormone Receptor-Positive Locally Advanced or Metastatic Breast Cancer.

    Science.gov (United States)

    Ohno, Shinji

    2016-08-01

    For women with hormone receptor-positive advanced breast cancer, endocrine therapies, including the selective estrogen receptor modulator tamoxifen, the aromatase inhibitors anastrozole, letrozole, and exemestane, and the selective estrogen receptor degrader fulvestrant, are recommended in clinical guidelines. The addition of targeted agents such as everolimus or palbociclib to aromatase inhibitors are also recommended as treatment options. Chemotherapy remains an option, although clinical guidelines have recommended these agents be reserved for patients with immediately life-threatening disease or if resistance to endocrine therapy is known or suspected. The present review has consolidated the tolerability profiles of the agents approved for use in the treatment of hormone receptor-positive advanced or metastatic breast cancer based on phase III registration trial data. Endocrine therapies are generally well tolerated, although the addition of targeted therapies to aromatase inhibitors or fulvestrant appears to increase the proportion of patients experiencing adverse events, and palbociclib and chemotherapy appear to be more closely associated with serious adverse events, including neutropenia.

  10. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer.

    Science.gov (United States)

    Yuan, Ying; Li, Xiao-Fen; Chen, Jia-Qi; Dong, Cai-Xia; Weng, Shan-Shan; Huang, Jian-Jin

    2014-01-01

    Past studies have demonstrated that epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) and sensitive EGFR gene mutations. Gefitinib (Iressa(®)), the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood-brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.

  11. Technological advances in transurethral resection of the prostate: bipolar versus monopolar TURP.

    Science.gov (United States)

    Issa, Muta M

    2008-08-01

    One of the most significant recent advancements in transurethral resection of the prostate (TURP) is the incorporation of bipolar technology. Bipolar circuitry allows TURP to be performed in a normal saline environment, which addresses a fundamental concern of conventional monopolar TURP (i.e., the use of hypo-osmolar irrigation). As a result, the risks of dilutional hyponatremia and transurethral resection (TUR) syndrome are eliminated, allowing for longer and safer resection. This review discusses the principles and applications of electrosurgery in conventional monopolar as well as new bipolar saline-based TURP systems. This review also addresses the positive impact on patient safety and resident training.

  12. An Extremely Rare Case of Advanced Metastatic Small Cell Neuroendocrine Carcinoma of Sinonasal Tract

    Directory of Open Access Journals (Sweden)

    Yu Yu Thar

    2016-01-01

    Full Text Available Small cell neuroendocrine carcinoma (SNEC is a rare form of malignancy. It mainly presents as bronchogenic neoplasm, and the extrapulmonary form accounts for only 0.1% to 0.4% of all cancers. These extrapulmonary tumors have been described most frequently in the urinary bladder, prostate, esophagus, stomach, colon and rectum, gall bladder, head and neck, cervix, and skin. Primary SNEC of the sinonasal tract is extremely rare with only less than 100 cases reported in the literature. Because of extreme rarity and aggressiveness of the tumor, the management for this entity varies considerably mandating multimodality approach. In this paper, we report a patient presented with left-sided facial swelling, and the histopathologic examination confirmed primary SNEC of left sinonasal tract. The tumor involved multiple paranasal sinuses with invasion into the left orbit and left infratemporal fossa and metastasized to cervical lymph nodes and bone. The patient encountered devastating outcome in spite of optimal medical management and treatment with palliative chemotherapy highlighting the necessity for further research of primary SNEC of head and neck.

  13. Prostate cancer progression attributed to autonomic nerve development: potential for therapeutic prevention of localized and metastatic disease.

    Science.gov (United States)

    Fernández, Elena V; Price, Douglas K; Figg, William D

    2013-11-01

    In a study recently published in Science, Magnon et al. show that both the sympathetic and parasympathetic components of the autonomic nervous system play an integral part in the development and dissemination of prostate cancer (PCa). Inhibition of the sympathetic nervous system (SNS) and disruption of the adrenergic receptors, specifically Ardβ 2, resulted in the prevention of primary PCa tumor development in mice. The authors found that inhibition of the SNS is only successful in preventing murine tumor development if completed early enough, and the parasympathetic nervous system (PNS) predominates in later stages of PCa. Inhibition of the PNS by way of the cholinergic receptor, muscarinic 1 (Chrm1), caused mice to develop less metastases to the pelvic lymph nodes, intestines, and bones. A PCa progression scheme has been outlined where initial tumor engraftment is controlled by the SNS but then becomes less prominent than the PNS, which promotes metastasis. The investigators showed the dependence of the autonomic nervous system on development of PCa and present opportunities for prevention; further studies are needed to confirm these results in humans.

  14. Castration-resistant prostate cancer: from new pathophysiology to new treatment

    NARCIS (Netherlands)

    Sridhar, S.S.; Freedland, S.J.; Gleave, M.E.; Higano, C.; Mulders, P.; Parker, C.; Sartor, O.; Saad, F.

    2014-01-01

    CONTEXT: Until recently, the only approved agent for metastatic castration-resistant prostate cancer (mCRPC) was docetaxel chemotherapy. But over the last 5 years, significant advances in the field have led to the approval of five new agents, each with different mechanisms of action and demonstratin

  15. Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study.

    Science.gov (United States)

    Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana; Loriot, Yohann; Sternberg, Cora N; Higano, Celestia S; Iversen, Peter; Evans, Christopher P; Kim, Choung-Soo; Kimura, Go; Miller, Kurt; Saad, Fred; Bjartell, Anders S; Borre, Michael; Mulders, Peter; Tammela, Teuvo L; Parli, Teresa; Sari, Suha; van Os, Steve; Theeuwes, Ad; Tombal, Bertrand

    2017-02-01

    Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28-0.37; p<0.0001) and the risk of death by 23% (HR 0.77, 95% CI 0.67-0.88; p=0.0002). Median investigator-assessed rPFS was 20.0 mo (95% CI 18.9-22.1) in the enzalutamide arm and 5.4 mo (95% CI 4.1-5.6) in the placebo arm. Median OS was 35.3 mo (95% CI 32.2-not yet reached) in the enzalutamide arm and 31.3 mo (95% CI 28.8-34.2) in the placebo arm. At the time of the OS analysis, 167 patients in the placebo arm had crossed over to receive enzalutamide. The most common adverse events in the enzalutamide arm were fatigue, back pain, constipation, and arthralgia. This final analysis of PREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991.

  16. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.

    Science.gov (United States)

    Tumati, Vasu; Mathur, Sanjeev; Song, Kwang; Hsieh, Jer-Tsong; Zhao, Dawen; Takahashi, Masaya; Dobin, Timothy; Gandee, Leah; Solberg, Timothy D; Habib, Amyn A; Saha, Debabrata

    2013-05-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

  17. Recent developments in palliative chemotherapy for locally advanced and metastatic pancreas cancer

    Institute of Scientific and Technical Information of China (English)

    Soley; Bayraktar; Ulas; Darda; Bayraktar; Caio; Max; Rocha-Lima

    2010-01-01

    In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease.Until recently,the only treatment with an impact on survival was surgery.In the palliative setting,gemcitabine(Gem) has been a standard treatment for advanced pancreatic cancer since ...

  18. 转移性去势抵抗性前列腺癌化疗后预后的影响因素%Factors Influencing Prognosis of Metastatic Castration-resistant Prostate Cancer after Chemotherapy

    Institute of Scientific and Technical Information of China (English)

    庞华

    2014-01-01

    Objective To investigate prognostic factors of metastatic castration-resistant prostate cancer ( mCRPC ) trea-ted with docetaxel chemotherapy .Methods Age,Gleason score ,prostate-specific antigen ,blood baseline condition and hormone-sensitive time of 46 patients with mCRPC were recorded .Results Overall survival time of all patients was 3-45 months,the aver-age survival time was (21.34 ±2.13) months,median survival time was 19.36 months;cox regression analysis showed that Glea-son score,hemoglobin,hormone-sensitive time were related with the patient's survival time,RR values were 1.782,2.363 and 2.012,and P<0.05.Conclusion Gleason score,hemoglobin concentration ,and hormone-sensitive time before chemotherapy are prognostic factors of metastatic castration resistant prostate cancer .%目的:探讨采用多西紫杉醇化疗的转移性去势抵抗性前列腺癌( metastatic castration-resistant prostate canc-er,MCRPC)患者预后影响因素。方法以转移性去势抵抗性前列腺癌患者46例作为观察对象,记录患者化疗前年龄、Gleason评分、前列腺特异抗原(prostate-specific antigen,PSA)值、血常规等基线情况及激素敏感时间。结果患者总生存时间为3~45个月,平均生存期为(21.34±2.13)个月,中位生存时间为19.36个月;Cox回归结果提示,Gleason评分、血红蛋白水平、激素敏感时间与患者生存时间相关,RR值分别为1.782、2.363和2.012,且P<0.05。结论多西他赛化疗前Gleason评分、血红蛋白浓度及激素敏感时间,是转移性去势抵抗性前列腺癌患者的预后因素。

  19. Spirituality in men with advanced prostate cancer: "it's a holistic thing . . . it's a package".

    Science.gov (United States)

    Lepherd, Laurence

    2014-06-01

    Spirituality is often regarded as being helpful during an unwell person's journey but definitions of the concept can be confusing, and its use synonymously with religion can be misleading. This research sought to answer the question, "What is the nature of spirituality in men with advanced prostate cancer," and to discover the role spirituality may have in these men as they face the challenges of living with their disease. A qualitative approach and narrative method was used to explore the spirituality of nine men with advanced prostate cancer who volunteered to participate and to tell the story of their cancer journey with particular focus on their spirituality. The study found that spirituality for these men, who were all Caucasians, was a "holistic thing" that involved physical, psychosocial, and spiritual matters that enabled them to transcend the everyday difficulties of their journey. Through their spirituality they obtained greater comfort and peace of mind during what was for many of them a very traumatic time. The central theme in the men's stories was that of connectedness-to themselves, to their partners, sometimes to a higher being, to other people such as their family and friends, and to other aspects of their lives.

  20. Neuroendocrine differentiation in prostate cancer%前列腺癌的神经内分泌分化

    Institute of Scientific and Technical Information of China (English)

    Jingwen Wang; Yang Yao

    2008-01-01

    Hormonal therapy is an important treatment for advanced/metastatic prostate cancer. But it can induce neuroen-docrine (NE) differentiation in prostate cancer cells. These NE cells will secrete manifold neural peptide or hormones which can lead to androgen-independent growth of non-NE tumor cells. When this happens, hormonal therapy becomes useless and indicates bad prognosis. In this paper, the mechanism of neuroendocrine differentiation and its relationship with androgen-independent were reviewed.

  1. Gemcitabine and cisplatin in locally advanced and metastatic bladder cancer; 3- or 4-week schedule?

    DEFF Research Database (Denmark)

    Als, Anne Birgitte; Sengeløv, Lisa; Von Der Maase, Hans

    2008-01-01

    BACKGROUND: Chemotherapy with gemcitabine and cisplatin (GC) is an active regimen in advanced transitional cell carcinoma (TCC). Traditionally, GC has been administered as a 4-week schedule. However, an alternative 3-week schedule may be more feasible. Long-term survival data for the alternative 3...... intensity for gemcitabine was accordingly lower in the 4 week-schedule. The higher dose intensity of cisplatin in the 3-week schedule, did not lead to increased renal toxicity. In 13 patients with impaired renal function, cisplatin was split into 2 days, which was feasible and efficient. CONCLUSION...

  2. Predictive factors for response and prognostic factors for long-term survival in consecutive, single institution patients with locally advanced and/or metastatic transitional cell carcinoma following cisplatin-based chemotherapy

    DEFF Research Database (Denmark)

    Jessen, Christian; Agerbaek, Mads; Von Der Maase, Hans

    2009-01-01

    PURPOSE: The study was undertaken to identify pre-treatment clinical and histopathological factors of importance for response and survival after cisplatin-based combination chemotherapy, in patients with locally advanced or metastatic transitional cell carcinoma of the urothelium. PATIENTS...

  3. Phase I trial of PC-Spes2 in advanced hormone refractory prostate cancer.

    Science.gov (United States)

    Shabbir, Majid; Love, Julie; Montgomery, Bruce

    2008-03-01

    There are few treatment options for prostate cancer once it becomes hormone refractory, with a mean life expectancy of 9-12 months. During the period 1997-2002, a product known as PC-Spes, containing a mixture of extracts from eight herbs based on the principles of traditional Chinese medicine, was reported to inhibit prostate cancer cell growth in vitro and reduce PSA in patients with hormone refractory prostate cancer (HRPC). This product was withdrawn from the market in 2002 due to concerns over quality control and reported contamination with traces of warfarin, indomethacin and diethylstilbesterol. PC-spes2, manufactured by Active Botanicals Ltd. (UK) with strict, independently-conducted quality control, has demonstrated no contaminants by high pressure liquid chromatography and liquid chromatography/mass spectroscopy. This compound was investigated in a single-centre, prospective, open pilot study. Eighteen patients with HRPC, mean age 72, median Gleason sum 8 (range 4-9) and median PSA 110 (range 4-2870) with three consecutive monthly increases in PSA were studied. Ten patients withdrew during the study period with significant diarrhoea (8 out of the first 10 patients at one month and only 2 out of the last 8 due to an improved dosing schedule). At one month, 7 out of 10 patients had a drop in their PSA doubling time or PSA velocity, which was still apparent in 4 out of 5 patients still on trial at three months and all three patients still on trial at six months. No serious adverse events or derangement of coagulation were observed. PC-Spes2 offers renewed hope and a safe alternative treatment option for patients with advanced HRPC. Further investigation with phase II trials is warranted.

  4. Rationale for stereotactic body radiation therapy in treating patients with oligometastatic hormone-naïve prostate cancer

    Directory of Open Access Journals (Sweden)

    Onita eBhattasali

    2013-12-01

    Full Text Available Despite advances in treatment for metastatic prostate cancer, patients eventually progress to castrate-resistant disease and ultimately succumb to their cancer. Androgen deprivation therapy (ADT is the standard treatment for metastatic prostate cancer and has been shown to improve median time to progression and median survival time. Research suggests that castrate-resistant clones may be present early in the disease process prior to the initiation of ADT. These clones are not susceptible to ADT and may even flourish when androgen-responsive clones are depleted. Stereotactic body radiation therapy (SBRT is a safe and efficacious method of treating clinically localized prostate cancer and metastases. In patients with a limited number of metastatic sites, SBRT may have a role in eliminating castrate-resistant clones and possibly delaying progression to castrate-resistant disease.

  5. Selenoprotein gene variants, toenail selenium levels, and risk for advanced prostate cancer.

    Science.gov (United States)

    Geybels, Milan S; van den Brandt, Piet A; Schouten, Leo J; van Schooten, Frederik J; van Breda, Simone G; Rayman, Margaret P; Green, Fiona R; Verhage, Bas A J

    2014-03-01

    Lower selenium levels have been associated with increased risk of prostate cancer (PCa), and genetic variation in the selenoprotein genes selenoprotein P (SEPP1) and glutathione peroxidase 1 (GPX1) is thought to modify this relationship. We investigated whether the association between toenail selenium levels and advanced PCa risk in the prospective Netherlands Cohort Study is modified by common genetic variation in SEPP1 and GPX1. Toenail clippings were used to determine selenium levels and to isolate DNA for genotyping. This case-cohort study, which included 817 case subjects with advanced PCa and 1048 subcohort members, was analyzed with Cox regression models. All statistical tests were two-sided. Three genetic variants were associated with advanced (stage III/IV or IV) PCa risk: SEPP1 rs7579 (lower risk; P trend = .01), GPX1 rs17650792 (higher risk; P trend = .03), and GPX1 rs1800668 (lower risk; P trend = .005). Toenail selenium levels were inversely associated with advanced PCa risk, independently of common genetic variation in SEPP1 and GPX1.

  6. {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Sahoo, Ranjit Kumar [All India Institute of Medical Sciences, Department of Medical Oncology, BR Ambedkar Rotary Cancer Hospital, New Delhi (India); Seth, Amlesh [All India Institute of Medical Sciences, Department of Urology, New Delhi (India)

    2017-01-15

    The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic{sup 68}Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly {sup 177}Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and toxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity

  7. Clinical benefit of bone-targeted radiometabolic therapy with {sup 153}Sm-EDTMP combined with chemotherapy in patients with metastatic hormone-refractory prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ricci, Sergio; Pastina, Ilaria; Cianci, Claudia; Orlandini, Cinzia; Chioni, Aldo; Di Donato, Samantha [Hospital, Nuclear Medicine Service-PET Center, Rovigo (Italy); Boni, Giuseppe; Genovesi, Dario; Grosso, Mariano; AlSharif, Abedallatif; Mariani, Giuliano [Univ. of Pisa (Italy). Regional Center of Nuclear Medicine; Chiacchio, Serena [Univ. of Pisa (Italy). Regional Center of Nuclear Medicine; CNR Inst. of Clinical Physiology, Pisa (Italy); Francesca, Francesco [University Hospital, Pisa (Italy). Div. of Urology; Selli, Cesare [Univ. of Pisa (Italy). Section Urology; Rubello, Domenico [Nuclear Medicine Service-PET, Rovigo (Italy)

    2007-07-15

    Bone metastases are responsible for most of the morbidity associated with hormone-refractory prostate cancer (HRPC). {sup 153}Sm-ethylenediaminetetramethylene phosphonate ({sup 153}Sm-EDTMP) has been approved for palliation of painful skeletal metastases. We retrospectively investigated the possible synergistic effect on survival of {sup 153}Sm-EDTMP (given to HRPC patients for bone pain palliation) and chemotherapy. Forty-five HRPC patients were evaluated, with a median age of 71 years. The number of metastatic bone sites was {<=}10 in 25 patients and >10 in 20 patients. Median serum PSA was 224 ng/ml. Bone pain was mild in 6 patients, moderate in 16, severe in 22 and intolerable in 1. Fifteen patients were only treated with {sup 153}Sm-EDTMP (group A), while 30 patients also received chemotherapy (estramustine phosphate or mitoxantrone plus prednisone) at variable times: between 3 and 5 months after {sup 153}Sm-EDTMP (14 patients, group B) or within 1 month after {sup 153}Sm-EDTMP (16 patients, group C). Haematological toxicities observed after either regimen were in general mild, consistent with common observations after either {sup 153}Sm-EDTMP or chemotherapy, and without any additive adverse effects in the patients receiving both {sup 153}Sm-EDTMP and chemotherapy. Bone pain palliation to some degree was induced by {sup 153}Sm-EDTMP in 32/45 patients (71.1%), the proportion of patients with a favourable clinical response being significantly higher in group C than in group A (87.5% vs 53.3%, p = 0.0388). Also in terms of biochemical response (serum PSA levels), patients of group C performed significantly better than patients of group A (p = 0.0235). Overall median survival from the time of administration of {sup 153}Sm-EDTMP was 15 months in the total cohort of 45 patients, and was significantly longer in group C than in either group B (30 months vs 11 months, p = 0.023) or group A (30 months vs 10 months, p = 0.008). The results of this study confirm that

  8. Xanthohumol impairs human prostate cancer cell growth and invasion and diminishes the incidence and progression of advanced tumors in TRAMP mice.

    Science.gov (United States)

    Venè, Roberta; Benelli, Roberto; Minghelli, Simona; Astigiano, Simonetta; Tosetti, Francesca; Ferrari, Nicoletta

    2012-12-06

    Despite recent advances in understanding the biological basis of prostate cancer, management of the disease, especially in the phase resistant to androgen ablation, remains a significant challenge. The long latency and high incidence of prostate carcinogenesis provides the opportunity to intervene with chemoprevention to prevent or eradicate prostate malignancies. In this study, we have used human hormone-resistant prostate cancer cells, DU145 and PC3, as an in vitro model to assess the efficacy of xanthohumol (XN) against cell growth, motility and invasion. We observed that treatment of prostate cancer cells with low micromolar doses of XN inhibits proliferation and modulates focal adhesion kinase (FAK) and AKT phosphorylation leading to reduced cell migration and invasion. Oxidative stress by increased production of reactive oxygen species (ROS) was associated with these effects. Transgenic adenocarcinoma of the mouse prostate (TRAMP) transgenic mice were used as an in vivo model of prostate adenocarcinoma. Oral gavage of XN, three times per week, beginning at 4 wks of age, induced a decrease in the average weight of the urogenital (UG) tract, delayed advanced tumor progression and inhibited the growth of poorly differentiated prostate carcinoma. The ability of XN to inhibit prostate cancer in vitro and in vivo suggests that XN may be a novel agent for the management of prostate cancer.

  9. {sup 99m}Tc(V)DMSA quantitatively predicts {sup 188}Re(V)DMSA distribution in patients with prostate cancer metastatic to bone

    Energy Technology Data Exchange (ETDEWEB)

    Blower, P.J.; Kettle, A.G.; O' Doherty, M.J.; Coakley, A.J. [Kent and Canterbury Hospital, Canterbury (United Kingdom). Nuclear Medicine Dept.; Knapp, F.F. Jr. [Nuclear Medicine Group, Oak Ridge National Lab., Oak Ridge, TN (United States)

    2000-09-01

    Rhenium-188 dimercaptosuccinic acid complex [{sup 188}Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent {sup 99m}Tc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if {sup 99m}Tc(V)DMSA could be used to predict tumour and kidney retention of {sup 188}Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of {sup 99m}Tc(V)DMSA and {sup 188}Re(V)DMSA. This would determine whether a scan with {sup 99m}Tc(V)DMSA, could be used to identify patients for whom {sup 188}Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in {sup 188}Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent {sup 99m}Tc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq {sup 99m}Tc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq {sup 188}Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the {sup 188}Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on {sup 188}Re scans than on {sup 99m}Tc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for {sup 188}Re than for {sup 99m}Tc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were

  10. Advanced Imaging for the Early Diagnosis of Local Recurrence Prostate Cancer after Radical Prostatectomy

    Directory of Open Access Journals (Sweden)

    Valeria Panebianco

    2014-01-01

    Full Text Available Currently the diagnosis of local recurrence of prostate cancer (PCa after radical prostatectomy (RT is based on the onset of biochemical failure which is defined by two consecutive values of prostate-specific antigen (PSA higher than 0.2 ng/mL. The aim of this paper was to review the current roles of advanced imaging in the detection of locoregional recurrence. A nonsystematic literature search using the Medline and Cochrane Library databases was performed up to November 2013. Bibliographies of retrieved and review articles were also examined. Only those articles reporting complete data with clinical relevance for the present review were selected. This review article is divided into two major parts: the first one considers the role of PET/CT in the restaging of PCa after RP; the second part is intended to provide the impact of multiparametric-MRI (mp-MRI in the depiction of locoregional recurrence. Published data indicate an emerging role for mp-MRI in the depiction of locoregional recurrence, while the performance of PET/CT still remains unclear. Moreover Mp-MRI, thanks to functional techniques, allows to distinguish between residual glandular healthy tissue, scar/fibrotic tissue, granulation tissue, and tumour recurrence and it may also be able to assess the aggressiveness of nodule recurrence.

  11. Phase I study of intermittent and chronomodulated oral therapy with capecitabine in patients with advanced and/or metastatic cancer

    Directory of Open Access Journals (Sweden)

    Gasparro Simona

    2006-02-01

    Full Text Available Abstract Background The combination of capecitabine and gemcitabine at Fixed Dose Rate (FDR has been demonstrated to be well tolerated, with apparent efficacy in patients with advanced cancers. FDR gemcitabine infusion leads to enhanced intracellular accumulation of drug and possible augmented clinical effect. The goals of this phase I study were to determine the maximum-tolerated dose (MTD of chronomodulated capecitabine in patients with advanced cancer and to describe the dose-limiting toxicities (DLT, the safety profile of this way of administration. Methods Patients with advanced solid tumours who had failed to response to standard therapy or for whom no standard therapy was available were elegible for this study. Capecitabine was administered orally according to following schedule: 1/4 of dose at 8:00 a.m.; 1/4 of dose at 6:00 p.m. and 1/2 of dose at 11:00 p.m. each day for 14 consecutive days, followed by a 7-day rest period. Results All 27 patients enrolled onto the study were assessable for toxicity. The most common toxicities during the first two cycles of chemotherapy were fatigue, diarrhoea and hand foot syndrome (HFS. Only one out of the nine patients treated at capecitabine dose of 2,750 mg/m2 met protocol-specified DLT criteria (fatigue grade 4. However, at these doses the majority of cycles of therapy were delivered without dose reduction or delay. No other episodes of DLT were observed at the same dose steps and at the lower dose steps of capecitabine (1,500/1,750/2,000/2,250/2,500 mg/m2. The dose of 2,750 mg/m2 is recommended for further study. Tumor responses were observed in patients with metastatic breast and colorectal cancer. Conclusion High doses of chronomodulated capecitabine can be administered with acceptable toxicity. The evidence of antitumor activity deserves further investigation in phase II combination chemotherapy studies.

  12. Advances in Variations of Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor-2 Status in Metastatic Breast Cancer

    Institute of Scientific and Technical Information of China (English)

    Yuan Yuan; Zhang Lili

    2013-01-01

    Chemotherapy, endocrine therapy and molecular targeted therapy are vital means in the treatment of metastatic breast cancer (MBC), whose reasonable and standard applications are of great importance to prolong patients’ survival and improve the quality of life. The expressions of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER-2) present signiifcant differences between primary and metastatic breast cancer. However, these differences may affect the selection of MBC patients for therapeutic strategies and judgment on the prognosis. Hence, the relevant researches on variations of hormone receptors and HER-2 in primary and metastatic breast cancer, discordant causes of ER, PR and HER-2 expression in primary and metastatic lesions and clinical value of biopsy to the metastases are reviewed in the study.

  13. 前列腺特异性膜抗原为靶标的放射免疫治疗进展%Advances in radioimmunotherapy targeting prostate speciifc membrane antigen in prostate cancer

    Institute of Scientific and Technical Information of China (English)

    刘冲(综述); 陶嵘(审校)

    2015-01-01

    前列腺特异性膜抗原(PSMA)是一种跨膜糖蛋白,几乎表达于所有前列腺癌,在转移性激素抵抗性前列腺癌中表达量显著增加。放射免疫治疗(RIT)利用放射性核素标记单克隆抗体以实现肿瘤的靶向治疗。本文对PSMA为靶标的RIT进展作一综述。%Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein, which is almost expressed in all prostate cancers. The expression of PSMA in metastatic hormone-refractory prostate cancer is significantly increased. Radioimmunotherapy combined radionuclide with monoclonal antibody is a kind of targeted cancer therapy. This review will summarize the progress of radioimmunotherapy targeting PSMA.

  14. Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5

    NARCIS (Netherlands)

    K. Fizazi (Karim); R. Jones (Robert); S. Oudard (Stéphane); E. Efstathiou (Eleni); F. Saad (Fred); R. de Wit (Ronald); J.S. de Bono (Johann); F.M. Cruz (Felipe Melo); G. Fountzilas (George); A. Ulys (Albertas); F. Carcano (Flavio); N. Agarwal (Neeraj); D. Agus (David); J. Bellmunt (Joaquim); D.P. Petrylak (Daniel P); S.-Y. Lee (Shih-Yuan); I.J. Webb (Iain J.); B. Tejura (Bindu); N. Borgstein (Niels); R. Dreicer (Robert)

    2015-01-01

    textabstractPurpose: Orteronel (TAK-700) is an investigational, nonsteroidal, reversible, selective 17,20-lyase inhibitor. This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy. Patients and Methods: In our study, 1,099

  15. Systematic Review and Meta-Analysis on the Role of Chemotherapy in Advanced and Metastatic Neuroendocrine Tumor (NET.

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    Matthew H Wong

    Full Text Available In the era of somatostatin analogues and targeted therapies, the role of chemotherapy in NET remains largely undefined. This systematic review aimed to assess the effect of chemotherapy on response rates (RR, progression-free survival (PFS, overall survival (OS and toxicity compared to other chemotherapies/systemic therapies or best supportive care in patients with advanced or metastatic NET.Randomised controlled trials (RCTs from 1946 to 2015 were identified from MEDLINE, EMBASE, other databases and conference proceedings. Review of abstracts, quality assessment and data abstraction were performed independently by two investigators. Meta-analyses were conducted using Mantel-Haenszel analysis with random-effects modelling.Six RCTs comparing standard streptozotocin plus 5-fluorouacil (STZ/5FU chemotherapy to other chemotherapy regimens, and 2 comparing this to interferon (IFN were included. Only 1 study was considered at low risk of bias. STZ/5-FU was no different to other chemotherapies in response rate [RR 0.96; 95% confidence interval (CI 0.72-1.27], PFS (RR 0.95; CI 0.81-1.13, or OS (RR 1.03; CI 0.77-1.39. IFN may produce higher response than STZ/5FU (RR 0.20; CI 0.04-1.13, but event rates were small and survival was no different. Interferon was associated with higher overall haematological (RR 0.47; CI 0.27-0.82 and lower overall renal toxicity (RR 3.61; CI 1.24-10.51.Strong evidence is lacking in the area of chemotherapy in neuroendocrine tumors. There is currently no evidence that one chemotherapeutic regimen is significantly better than the other, nor is interferon better than chemotherapy. There is an urgent need to design RCTs comparing modern chemotherapy to other agents in NET.

  16. Evaluation of the efficacy and toxicity of protocol cisplatin, 5-fluorouracil, leucovorin compared to protocol fluorouracil, doxorubicin and mitomycin C in locally advanced and metastatic gastric cancer

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    Andrić Zoran

    2012-01-01

    Full Text Available Introduction. Still there is no consensus on the choice of the most efficient and the least toxic chemotherapy regimen in the treatment of advanced gastric cancer. Nowadays few therapy protocols are available for treating this disease. Objective. Study was conducted to compare the efficacy and toxicity of FAM (flurouracil, doxorubicin, mitomycin C with CDDP and FU/FA (cisplatin, 5-fluorouracil, leucovorin protocols in patients with locally advanced and metastatic gastric cancer. Methods. This randomized study involved a group of 50 patients with locally advanced or metastatic gastric cancer, who had not previously undergone chemotherapy treatment. Progression free survival, overall survival and drug toxicity were evaluated. For statistical analysis chi-square test, Kaplan-Meier curve and the log rank test were used. Results. The overall response rate was 20% in the group treated with FAM and 24% in the group treated with CDDP, FU/FA (4% of patients from each group had complete response, but without significant statistical difference. Median survival was 10.9 months in the FAM group and 11.8 months in CDDP, FU/FA group, with no statistically significant difference. Non-haematological and haematological toxicities of CDDP, FU/FA were considerably less frequent than of FAM, and there was no treatment related deaths in any of the groups. Conclusion. Both investigated regimens demonstrated moderate efficacy. The study shows in favour of justified application of both protocols, while in regard to toxicity CDDP and FU/FA can be recommended as preferable treatment for locally advanced and metastatic gastric cancer. New strategies should be considered for better efficacy in the treatment of advanced gastric cancer. New strategies are necessary with the goal to achieve a better therapeutic effect.

  17. Prostate cancer patients may have an increased risk of coexisting advanced colorectal neoplasms

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    Ko SH

    2016-09-01

    Full Text Available Sun-Hye Ko,1,2 Myong Ki Baeg,2,3 Woong Jin Bae,4 Pumsoo Kim,3 Myung-Gyu Choi2 1Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; 2Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 3Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon, South Korea; 4Department of Urology, College of Medicine, The Catholic University of Korea, Seoul, South Korea Background/aims: Patients being treated for prostate cancer (PCa have an increased risk of developing colorectal cancer. However, whether PCa patients are inherently at a higher risk of colorectal neoplasms (CRNs is unknown. We aimed to investigate the risk of CRNs in PCa patients.Materials and methods: Patients who had been diagnosed with PCa at a tertiary medical center and had colonoscopy within 1 year of the PCa diagnosis were investigated. Patients were propensity-matched 1:2 by age and body mass index to asymptomatic control subjects who had undergone colonoscopy for routine health screening. CRN was defined as histological confirmation of an adenoma or adenocarcinoma component. Advanced CRN was defined as any of the following: 1 histological findings of high-grade dysplasia, 2 inclusion of villous features, 3 tumor ≥1 cm in size, or 4 presence of an adenocarcinoma. Risk factors for CRN and advanced CRN were evaluated by univariate and multivariate analysis.Results: A total of 191 patients diagnosed with PCa had colonoscopies within 1 year of PCa diagnosis. Of these, 23 patients with a history of previous malignancy and seven with incomplete colonoscopies were excluded, leaving 161 patients in the PCa group. Although presence of PCa was not a significant risk factor for CRN by multivariate analysis, PCa was a significant risk factor for advanced CRN (odds ratio [OR] 3.300; 95% confidence interval [CI] 1.766–6.167; P<0

  18. PROGNOSTIC FACTORS OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY FOR LOCALIZED AND LOCALLY-ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    V. A. Chernyaev

    2014-08-01

    Full Text Available Purpose. To reveal prognostic factors of PSA-failure following radical prostatectomy in patients with localized and locally-advanced prostate cancer.Materials and methods. Medical data of 386 consecutive patients with localized and locally-advanced prostate cancer who underwent radical prostatectomy from 1997 to 2011 were analyzed. Median age was 61.0 years. Median PSA before surgery – 10.3 ng/ml. Plasma levels of VEGF, VEGFR2, VEGFR3, TGF-β1, CD105, IL-6 were measured using Enzyme Linked-Immuno-Sorbent Assay (ELISA before radical prostatectomy in 77 patients. Postoperatively the tumours were categorized as pT2 in 288 (59.1 %, pT3 – in 144 (37.3 %, pT4 – in 14 (3.6; pN+ – in 34 (8.8 % cases. Gleason score < 7 was present in 254 (65.8 %,  7 – in 132 (34.2 % specimens. Perineural invasion was identified in 188 (48.7 %, angiolymphatic invasion – in 126 (32.6 cases.Results. Biochemical recurrence occurred in 64 (16.6 % out of 386 patients at a median follow-up of 30.5 (12−164 months. Independent predictors of biochemical recurrence were PSA (HR 0.161 (95% CI:0.058−0.449; р = 0.001, Gleason sum in surgical specimens (HR 0.496 (95 % CI:0.268−0.917; p = 0.025, pN (HR 0.415 (95 % CI:0.181−0.955; p = 0.039. The patients were divided into 3 prognostic groups: good (0 factor, intermediate (1 factor, poor (2 factors and very poor (3 factors (AUC – 0.720 (95% CI: 0.656−0.784. High preoperative levels VEGF ( 67 pg/ml (р = 0.005, VEGFR2 ( 3149 pg/ml (р = 0.036, VEGFR3 ( 2268 pg/ml (р = 0.001, TGF-β1 ( 14473 pg/ml (р = 0.052 were identified as unfavorable prognostic factors for survival without PSA-failure. Conclusion. Independent prognostic factors of biochemical recurrence after prostatectomy were PSA, Gleason sum and pN. Joint effect of the factors allows to predict PSA-relapse with accuracy 0.720. Preoperative serum levels VEGF, VEGFR2, VEGFR3, TGF-β1 potentially are perspective markers for PSA-failure after

  19. PROGNOSTIC FACTORS OF BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY FOR LOCALIZED AND LOCALLY-ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    V. A. Chernyaev

    2012-01-01

    Full Text Available Purpose. To reveal prognostic factors of PSA-failure following radical prostatectomy in patients with localized and locally-advanced prostate cancer.Materials and methods. Medical data of 386 consecutive patients with localized and locally-advanced prostate cancer who underwent radical prostatectomy from 1997 to 2011 were analyzed. Median age was 61.0 years. Median PSA before surgery – 10.3 ng/ml. Plasma levels of VEGF, VEGFR2, VEGFR3, TGF-β1, CD105, IL-6 were measured using Enzyme Linked-Immuno-Sorbent Assay (ELISA before radical prostatectomy in 77 patients. Postoperatively the tumours were categorized as pT2 in 288 (59.1 %, pT3 – in 144 (37.3 %, pT4 – in 14 (3.6; pN+ – in 34 (8.8 % cases. Gleason score < 7 was present in 254 (65.8 %,  7 – in 132 (34.2 % specimens. Perineural invasion was identified in 188 (48.7 %, angiolymphatic invasion – in 126 (32.6 cases.Results. Biochemical recurrence occurred in 64 (16.6 % out of 386 patients at a median follow-up of 30.5 (12−164 months. Independent predictors of biochemical recurrence were PSA (HR 0.161 (95% CI:0.058−0.449; р = 0.001, Gleason sum in surgical specimens (HR 0.496 (95 % CI:0.268−0.917; p = 0.025, pN (HR 0.415 (95 % CI:0.181−0.955; p = 0.039. The patients were divided into 3 prognostic groups: good (0 factor, intermediate (1 factor, poor (2 factors and very poor (3 factors (AUC – 0.720 (95% CI: 0.656−0.784. High preoperative levels VEGF ( 67 pg/ml (р = 0.005, VEGFR2 ( 3149 pg/ml (р = 0.036, VEGFR3 ( 2268 pg/ml (р = 0.001, TGF-β1 ( 14473 pg/ml (р = 0.052 were identified as unfavorable prognostic factors for survival without PSA-failure. Conclusion. Independent prognostic factors of biochemical recurrence after prostatectomy were PSA, Gleason sum and pN. Joint effect of the factors allows to predict PSA-relapse with accuracy 0.720. Preoperative serum levels VEGF, VEGFR2, VEGFR3, TGF-β1 potentially are perspective markers for PSA-failure after

  20. Advancing the Capabilities of an Authentic Ex Vivo Model of Primary Human Prostate Cancer

    Science.gov (United States)

    2014-10-01

    benign and prostate cancer (PCa) TSCs in the absence of androgen for 5 days resulted in heterogeneous reduction of cellular viability and glandular ...tumor xenografts. J Clin Invest 2011;121:2383–2390. 21. Kiviharju-af Hallstrom TM, Jaamaa S, Monkkonen M, et al. Human prostate epithelium lacks Wee1A...al. Contrasting DNA damage checkpoint responses in epithelium of the human seminal vesicle and prostate. Prostate 2012;72:1060–1070. 25. Behrsing HP

  1. A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment

    Science.gov (United States)

    2015-10-01

    Figure 6: A. Picture of 25 weeks old TRAMP mice bearing prostate tumor. B. PKD1 and MTA1 protein levels in prostate tissues of TRAMP (TG) and their wild...Verras, M. and Z. Sun , Roles and regulation of Wnt signaling and beta-catenin in prostate cancer. Cancer Lett, 2006. 237(1): p. 22-32. 5. Sarkar, F.H

  2. Clinical Characteristics of Prostate Cancer in Advanced Stage and Its Treatment by Chinese and Western Medicine

    Institute of Scientific and Technical Information of China (English)

    张亚强; 宋竖旗

    2009-01-01

    Prostate cancer is a common malignant tumor in male seniors,with the higher rates in the Europe and America.There has been obvious increase in the incidence of prostate cancer in China recently.It has been reported that the incidence of prostate cancer was only

  3. New developments in the treatment of castration resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    Roxanne Wadia

    2014-08-01

    Full Text Available In the past 5 years, the treatment and understanding of metastatic castrate resistant prostate cancer (CRPC have improved dramatically. Our understanding of the mechanisms of castration resistance has allowed for the development of new drugs to target prostate cancer, and our understanding of genetic mutations may give us new tools with which to more accurately diagnose and be able to predict the course of this heterogeneous disease. This article summarizes the recent advances in the understanding of the development of CRPC, as well as the new drugs and targets, which have evolved from this basic research.

  4. Current state of prostate cancer treatment in Jamaica.

    Science.gov (United States)

    Morrison, Belinda F; Aiken, William D; Mayhew, Richard

    2014-01-01

    Prostate cancer is the commonest cancer in Jamaica as well as the leading cause of cancer-related deaths. One report suggested that Jamaica has the highest incidence rate of prostate cancer in the world, with an age-standardised rate of 304/100,000 per year. The Caribbean region is reported to have the highest mortality rate of prostate cancer worldwide. Prostate cancer accounts for a large portion of the clinical practice for health-care practitioners in Jamaica. The Jamaica Urological Society is a professional body comprising 19 urologists in Jamaica who provide most of the care for men with prostate cancer in collaboration with medical oncologists, radiation oncologists, and a palliative care physician. The health-care system is structured in two tiers in Jamaica: public and private. The urologist-to-patient ratio is high, and this limits adequate urological care. Screening for prostate cancer is not a national policy in Jamaica. However, the Jamaica Urological Society and the Jamaica Cancer Society work synergistically to promote screening as well as to provide patient education for prostate cancer. Adequate treatment for localised prostate cancer is available in Jamaica in the forms of active surveillance, nerve-sparing radical retropubic prostatectomy, external beam radiation, and brachytherapy. However, there is a geographic maldistribution of centres that provide prostate cancer treatment, which leads to treatment delays. Also, there is difficulty in affording some treatment options in the private health-care sectors. Androgen deprivation therapy is available for treatment of locally advanced and metastatic prostate cancer and is subsidised through a programme called the National Health Fund. Second-line hormonal agents and chemotherapeutic agents are available but are costly to most of the population. The infrastructure for treatment of prostate cancer in Jamaica is good, but it requires additional technological advances as well as additional specialist

  5. Loss of PDEF, a prostate-derived Ets factor is associated with aggressive phenotype of prostate cancer: Regulation of MMP 9 by PDEF

    Directory of Open Access Journals (Sweden)

    Meacham Randall B

    2010-06-01

    Full Text Available Abstract Background Prostate-derived Ets factor (PDEF is expressed in tissues of high epithelial content including prostate, although its precise function has not been fully established. Conventional therapies produce a high rate of cure for patients with localized prostate cancer, but there is, at present, no effective treatment for intervention in metastatic prostate cancer. These facts underline the need to develop new approaches for early diagnosis of aggressive prostate cancer patients, and mechanism based anti-metastasis therapies that will improve the outlook for hormone-refractory prostate cancer. In this study we evaluated role of prostate-derived Ets factor (PDEF in prostate cancer. Results We observed decreased PDEF expression in prostate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Loss of PDEF expression was confirmed in high Gleason Grade prostate cancer samples by immuno-histochemical methods. Reintroduction of PDEF profoundly affected cell behavior leading to less invasive phenotypes in three dimensional cultures. In addition, PDEF expressing cells had altered cell morphology, decreased FAK phosphorylation and decreased colony formation, cell migration, and cellular invasiveness. In contrast PDEF knockdown resulted in increased migration and invasion as well as clonogenic activity. Our results also demonstrated that PDEF downregulated MMP9 promoter activity, suppressed MMP9 mRNA expression, and resulted in loss of MMP9 activity in prostate cancer cells. These results suggested that loss of PDEF might be associated with increased MMP9 expression and activity in aggressive prostate cancer. To confirm results we investigated MMP9 expression in clinical samples of prostate cancer. Results of these studies show increased MMP9 expression correlated with advanced Gleason grade. Taken together our results demonstrate decreased PDEF expression

  6. Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Wang Y

    2016-06-01

    Full Text Available Yuan Wang,1 Guo-fang Hu,1 Qian-qian Zhang,1 Ning Tang,1 Jun Guo,2 Li-yan Liu,2 Xiao Han,2 Xia Wang,2 Zhe-hai Wang2 1School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, 2Shandong Cancer Hospital, Shandong University, Jinan, Shandong, People’s Republic of China Background: Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo for patients with advanced pancreatic cancer using the currently available evidence. Methods: PubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively. Results: A total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%–17.7%, disease control rate was 55.0% (95% CI: 51.5%–58.5%, and 1-year survival rate was 28.5% (95% CI: 24.0%–33.4%. Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As

  7. EMP combination chemotherapy and low-dose monotherapy in advanced prostate cancer.

    Science.gov (United States)

    Kitamura, Tadaichi; Nishimatsu, Hiroaki; Hamamoto, Toshiaki; Tomita, Kyoichi; Takeuchi, Takumi; Ohta, Nobutaka

    2002-02-01

    Many chemotherapeutic regimens combined with estramustine phosphate (EMP) have been elaborated for the treatment of hormone-refractory prostate cancer over 30 years. However, older EMP-based combination chemotherapies with vinblastine, vinorelbine, doxorubicin or cyclophosphamide showed relatively low PSA response rate (25-58%) accompanied with high toxicities. On the other hand, newly developed EMP-based combination regimens with etoposide, pacitaxel, carboplatin or docetaxel demonstrated promising PSA response rate (43-77%) with moderate to severe toxicity in the rate of thromboembolic event (5-18%) and of neutropenia (9-41%). Treatment-related death was less in the latter combination group (5/615, 0.8%) than that in the former group (3/234, 1.3%). Of note, in the docetaxel combination with EMP, PSA response rate is as high as 77% with high rate (41%) of neutropenia but no treatment-related death was observed. Docetaxel combination with EMP seems to be the best regimen, though not completely justified by randomized trials, to be selected in the modern era, which will be followed by paclitaxel, carboplatin and EMP combination with PSA response rate of 71%. In addition, an interim report in 83 patients was presented. They were not consecutively enrolled but were treated on low-dose EMP monotherapy for previously untreated advanced prostate cancer in Department of Urology of Tokyo University and our 21 affiliated hospitals. Overall PSA response rate was as high as 93.4% out of 76 assessable patients. However, overall toxicity rate was abnormally high (39.5%) with drug discontinuation rate of 32.1%. The reason of low drug compliance may be attributed to gastrointestinal symptoms. To overcome the low drug compliance, appropriate patients for EMP administration should be selected by using gene analysis on the basis of sophisticated tailor-made medicine.

  8. Pemetrexed single agent chemotherapy in previously treated patients with locally advanced or metastatic non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Bearz Alessandra

    2008-07-01

    Full Text Available Abstract Background The main objective of this study was to evaluate the safety of second-line pemetrexed in Stage IIIB or IV NSCLC. Methods Overall, 95 patients received pemetrexed 500 mg/m2 i.v. over Day 1 of a 21-day cycle. Patients also received oral dexamethasone, oral folic acid and i.m. vitamin B12 supplementation to reduce toxicity. NCI CTC 2.0 was used to rate toxicity. All the adverse events were graded in terms of severity and relation to study treatment. Dose was reduced in case of toxicity and treatment was delayed for up to 42 days from Day 1 of any cycle to allow recovering from study drug-related toxicities. Tumor response was measured using the RECIST criteria. Results Patients received a median number of 4 cycles and 97.8% of the planned dose. Overall, 75 patients (78.9% of treated reported at least one adverse event: 34 (35.8% had grade 3 as worst grade and only 5 (5.2% had grade 4. Drug-related events occurred in 57.9% of patients. Neutropenia (8.4% and leukopenia (6.3 % were the most common grade 3/4 hematological toxicities. Grade 3 anemia and thrombocytopenia were reported in 3.2% and 2.1% of patients, respectively. Diarrhea (6.3%, fatigue (3.2% and dyspnea (3.2% were the most common grade 3/4 non-hematological toxicities. The most common drug-related toxicities (any grade were pyrexia (11.6%, vomiting, nausea, diarrhea and asthenia (9.5% and fatigue (8.4%. Tumor Response Rate (CR/PR in treated patients was 9.2%. The survival at 4.5 months (median follow-up was 79% and the median PFS was 3.1 months. Twenty patients (21.1% died mainly because of disease progression. Conclusion Patients with locally advanced or metastatic NSCLC could benefit from second-line pemetrexed, with a low incidence of hematological and non-hematological toxicities.

  9. Prostate cancer is not breast cancer

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    Ajit Venniyoor

    2016-01-01

    Full Text Available Cancers of the prostate and breast are hormone dependent cancers. There is a tendency to equate them and apply same algorithms for treatment. It is pointed out that metastatic prostate cancer with bone-only disease is a potentially fatal condition with a much poorer prognosis than metastatic breast cancer and needs a more aggressive approach.

  10. Evaluation of Alpha-Therapy with Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—the Role of Gamma Scintigraphy in Dosimetry and Pharmacokinetics

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    Kalevi Kairemo

    2015-07-01

    Full Text Available Radium-223-dichloride (223RaCl2 is a new bone-seeking calcium analogue alpha-emitter, which has obtained marketing authorization for the treatment skeletal metastases of hormone-refractory prostate cancer. The current treatment regimen is based on six consecutive doses of 223RaCl2 at 4 week intervals and the administered activity dose, 50 kBq/kg per cycle is based on patient weight. We analyzed two patients using quantitative serial gamma imaging to estimate dosimetry in tumors and see possible pharmacokinetic differences in the treatment cycles. The lesions were rather well visualized in gamma scintigraphy in spite of low gamma activity (<1.1% gamma radiation at 0, 7 and 28 days using 30–60 min acquisition times. Both our patients analyzed in serial gamma imagings, had two lesions in the gamma imaging field, the mean counts of the relative intensity varied from 27.8 to 36.5 (patient 1, and from 37.4 to 82.2 (patient 2. The half-lives varied from 1.8 days to 4.5 days during the six cycles (patient 1, and from 1.5 days to 3.6 days (patient 2, respectively. In the lesion half-lives calculated from the imaging the maximum difference between the treatment cycles in the same lesion was 2.0-fold (1.8 vs. 3.6. Of these patients, patient 1 demonstrated a serum PSA response, whereas there was no PSA response in patient 2. From our data, there were maximally up to 4.0-fold differences (62.1 vs. 246.6 between the relative absorbed radiation doses between patients as calculated from the quantitative standardized imaging to be delivered in only two lesions, and in the same lesion the maximum difference in the cycles was up to 2.3-fold (107.4 vs. 246.6. Our recommendation based on statistical simulation analysis, is serial measurement at days 0–8 at least 3 times, this improve the accuracy significantly to study the lesion activities, half-lives or calculated relative absorbed radiation doses as calculated from the imaging. Both our patients had

  11. Efficacy and safety of second-line agents for treatment of metastatic castration-resistant prostate cancer progressing after docetaxel. A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Gianpaolo Perletti

    2015-07-01

    Full Text Available Objective: We performed a systematic review of the literature to assess the efficacy and the safety of second-line agents targeting metastatic castration-resistant prostate cancer (mCRPC that has progressed after docetaxel. Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel. Materials and Methods: We included phase III randomized controlled trials that enrolled patients with mCRPC progressing during or after first-line docetaxel treatment. Trials were identified by electronic database searching. The primary outcome of the review was overall survival. Secondary outcomes were radiographic progression-free survival (rPFS and severe adverse effects (grade 3 or higher. Results: Ten articles met the inclusion criteria for the review. These articles reported the results of five clinical trials, enrolling in total 5047 patients. The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. Compared to control cohorts (active drug-treated or placebotreated, the significant overall survival advantages achieved were 4.8 months for enzalutamide (hazard ratio for death vs. placebo: 0.63; 95% CI 0.53 to 0.75, P < 0.0001, 4.6 months for abiraterone (hazard ratio for death vs. placebo: 0.66, 95% CI 0.58 to 0.75, P < 0.0001 and 2.4 months for cabazitaxel (hazard ratio for death vs. mitoxantrone-prednisone: 0.70, 95% CI 0.59 to 0.83, p < 0.0001. Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P < 0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P < 0.00001. Androgen synthesis inhibitors induced significant increases in risk ratios for adverse effects

  12. Critical appraisal of the role of gefitinib in the management of locally advanced or metastatic non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Yuan Y

    2014-05-01

    Full Text Available Ying Yuan, Xiao-Fen Li, Jia-Qi Chen, Cai-Xia Dong, Shan-Shan Weng, Jian-Jin HuangDepartment of Medical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaAbstract: Past studies have demonstrated that epidermal growth factor receptor (EGFR tyrosine kinase inhibitors can significantly improve clinical outcomes in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC and sensitive EGFR gene mutations. Gefitinib (Iressa®, the first oral EGFR tyrosine kinase inhibitor, has been shown to be more effective and better tolerated than chemotherapy either in first-line or second-line treatment for patients with advanced NSCLC harboring sensitive EGFR mutations. Conversely, among patients with wild-type EGFR, gefitinib is inferior to standard chemotherapy in both the first-line and second-line settings. Further, gefitinib is effective in patients with brain metastases because of its low molecular weight and excellent penetration of the blood–brain barrier. In this review, we summarize the current data from clinical trials with gefitinib and appraise its role in the management of locally advanced or metastatic NSCLC.Keywords: gefitinib, non-small cell lung cancer, epidermal growth factor receptor, tyrosine kinase inhibitor

  13. Efficacy and safety of gemcitabine plus erlotinib for locally advanced or metastatic pancreatic cancer: a systematic review and meta-analysis

    Science.gov (United States)

    Wang, Yuan; Hu, Guo-fang; Zhang, Qian-qian; Tang, Ning; Guo, Jun; Liu, Li-yan; Han, Xiao; Wang, Xia; Wang, Zhe-hai

    2016-01-01

    Background Pancreatic cancer is considered as a chemoresistant neoplasm with extremely dismal prognosis. Gemcitabine is recommended as the standard agent for locally advanced or metastatic pancreatic cancer. A series of trials have been conducted to improve the outcome of advanced pancreatic cancer with other anticancer drugs in combination with gemcitabine. Unfortunately, the designers of the clinical trials failed to improve the poor prognosis of patients with advanced pancreatic cancer. Erlotinib was the first additional drug that improved the overall survival of patients with advanced pancreatic cancer with gemcitabine. We performed this systematic review and meta-analysis to explore the efficacy and safety of the combination of gemcitabine with erlotinib (GemErlo) for patients with advanced pancreatic cancer using the currently available evidence. Methods PubMed/MEDLINE, EMBASE, the Cochrane Library, and relevant abstracts of major conferences were comprehensively searched. Data results on objective response rate, disease control rate, and 1-year survival were pooled by using MetaAnalyst with a random-effects model. Results on progression-free survival and overall survival were only summarized descriptively. Results A total of 24 studies with 1,742 patients with locally advanced or metastatic pancreatic cancer treated with GemErlo were included. Combined objective response rate was 14.4% (95% CI: 11.6%–17.7%), disease control rate was 55.0% (95% CI: 51.5%–58.5%), and 1-year survival rate was 28.5% (95% CI: 24.0%–33.4%). Progression-free survival ranged from 2.63 to 9.6 months, and overall survival varied from 6 to 10 months. As for the toxicity profile, the most common adverse events (AEs) were hematologic reactions, skin rash, and gastrointestinal reactions. Other severe AEs, which had low incidence, included treatment-induced death and interstitial lung disease. Conclusion Our study showed that GemErlo is associated with reasonable activity in treating

  14. Imaging of Spinal Metastatic Disease

    Directory of Open Access Journals (Sweden)

    Lubdha M. Shah

    2011-01-01

    Full Text Available Metastases to the spine can involve the bone, epidural space, leptomeninges, and spinal cord. The spine is the third most common site for metastatic disease, following the lung and the liver. Approximately 60–70% of patients with systemic cancer will have spinal metastasis. Materials/Methods. This is a review of the imaging techniques and typical imaging appearances of spinal metastatic disease. Conclusions. Awareness of the different manifestations of spinal metastatic disease is essential as the spine is the most common site of osseous metastatic disease. Imaging modalities have complimentary roles in the evaluation of spinal metastatic disease. CT best delineates osseous integrity, while MRI is better at assessing soft tissue involvement. Physiologic properties, particularly in treated disease, can be evaluated with other imaging modalities such as FDG PET and advanced MRI sequences. Imaging plays a fundamental role in not only diagnosis but also treatment planning of spinal metastatic disease.

  15. The significance of early changes in serum alkaline-phosphatase levels following endocrine treatment in patients with advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Aditya Pareek

    2000-01-01

    Conclusions: A significant proportion of patients with advanced carcinoma of the prostate have flare in SAP le-vels soon after initiating the treatment. We confirm that the flare activity in SAP levels is a negative prognostic indicator and it is possible to identify early treatment fail-ures by frequent measurements of SAP levels during first 6 weeks of commencing the therapy. The significance of SAP fare and androgen resistance is discussed.

  16. Subcapsular Orchiectomy in the Primary Therapy of Patients with Bone Metastasis in Advanced Prostate Cancer: An Anachronistic Intervention?

    Directory of Open Access Journals (Sweden)

    Oleg Rud

    2012-01-01

    Full Text Available Background. The therapeutic impact of palliative androgen deprivation in metastatic prostate cancer is indisputable. Bilateral orchiectomy represents the traditional method of AD but was reduced during the last years in favor for treatment with LHRH analogues. Due to limited economic resources of the health care system, the economically priced definite surgical castration might experience a renaissance. Methods. In this single-center retrospective study, 83 consecutive patients with osseous metastasized prostate cancer were evaluated, who had primarily been treated by subcapsular bilateral orchiectomy. Response to therapy, time until therapy failure, overall survival time, psychological disorders due to loss of organ, and disease-associated and postoperative surgical complications were recorded. The median followup was 35 months (IQR: 26–46. Results. Patients' mean age at surgery was 72.1 (54–91 years. Six patients (7.2% displayed immediate tumor progression after orchiectomy. Median time of tumor remission and overall survival time were 29 and 36 months, respectively. 14% of the study group showed minor postoperative complications. No psychological problems occurred following bilateral orchiectomy. Conclusion. Due to an effective and persistent oncological effectiveness, less morbidity, and absence of psychological implications, bilateral subcapsular orchiectomy seems to be a practicable and advisable alternative in the first-line therapy of metastasized PCa.

  17. Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial

    NARCIS (Netherlands)

    Eertwegh, A.J. van den; Versluis, J.; Berg, H.P. van den; Santegoets, S.J.; Moorselaar, R.J. van; Sluis, T.M. van der; Gall, H.E.; Harding, T.C.; Jooss, K.; Lowy, I.; Pinedo, H.M.; Scheper, R.J.; Stam, A.G.; Blomberg, B.M. von; Gruijl, T.D. de; Hege, K.; Sacks, N.; Gerritsen, W.R.

    2012-01-01

    BACKGROUND: The granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells vaccine (GVAX) has antitumour activity against prostate cancer; preclinical studies have shown potent synergy when combined with ipilimumab, an antibody that blocks cytotoxic T-lymphocyte ant

  18. Sorafenib for Metastatic Thyroid Cancer

    Science.gov (United States)

    A summary of results from an international phase III trial that compared sorafenib (Nexavar®) and a placebo for the treatment of locally advanced or metastatic differentiated thyroid cancer that is no longer responding to treatment with radioactive iodine

  19. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

    Science.gov (United States)

    Shahabi, Ahva; Corral, Román; Catsburg, Chelsea; Joshi, Amit D; Kim, Andre; Lewinger, Juan Pablo; Koo, Jocelyn; John, Esther M; Ingles, Sue A; Stern, Mariana C

    2014-01-01

    The relationship between tobacco smoking and prostate cancer (PCa) remains inconclusive. This study examined the association between tobacco smoking and PCa risk taking into account polymorphisms in carcinogen metabolism enzyme genes as possible effect modifiers (9 polymorphisms and 1 predicted phenotype from metabolism enzyme genes). The study included cases (n = 761 localized; n = 1199 advanced) and controls (n = 1139) from the multiethnic California Collaborative Case–Control Study of Prostate Cancer. Multivariable conditional logistic regression was performed to evaluate the association between tobacco smoking variables and risk of localized and advanced PCa risk. Being a former smoker, regardless of time of quit smoking, was associated with an increased risk of localized PCa (odds ratio [OR] = 1.3; 95% confidence interval [CI] = 1.0–1.6). Among non-Hispanic Whites, ever smoking was associated with an increased risk of localized PCa (OR = 1.5; 95% CI = 1.1–2.1), whereas current smoking was associated with risk of advanced PCa (OR = 1.4; 95% CI = 1.0–1.9). However, no associations were observed between smoking intensity, duration or pack-year variables, and advanced PCa. No statistically significant trends were seen among Hispanics or African-Americans. The relationship between smoking status and PCa risk was modified by the CYP1A2 rs7662551 polymorphism (P-interaction = 0.008). In conclusion, tobacco smoking was associated with risk of PCa, primarily localized disease among non-Hispanic Whites. This association was modified by a genetic variant in CYP1A2, thus supporting a role for tobacco carcinogens in PCa risk. PMID:25355624

  20. Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

    Science.gov (United States)

    2016-06-09

    Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

  1. Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer

    DEFF Research Database (Denmark)

    Iversen, Peter; McLeod, David G; See, William A;

    2010-01-01

    To evaluate the efficacy and tolerability of bicalutamide 150 mg once-daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy.......To evaluate the efficacy and tolerability of bicalutamide 150 mg once-daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy....

  2. Dietary flavonoid intake, black tea consumption, and risk of overall and advanced stage prostate cancer

    NARCIS (Netherlands)

    Geybels, M.S.; Verhage, B.A.J.; Arts, I.C.W.; Schooten, F.J. van; Goldbohm, R.A.; Brandt, P.A. van den

    2013-01-01

    Flavonoids are natural antioxidants found in various foods, and a major source is black tea. Some experimental evidence indicates that flavonoids could prevent prostate cancer. We investigated the associations between flavonoid intake, black tea consumption, and prostate cancer risk in the Netherlan

  3. Plasma levels of trefoil factors are increased in patients with advanced prostate cancer

    DEFF Research Database (Denmark)

    Vestergaard, E.M.; Borregaard, Michael Krabbe; Poulsen, Steen Seier;

    2006-01-01

    Through cDNA array analyses and immunohistochemistry on tissue microarrays, trefoil factor 3 (TFF3) was recently shown to be overexpressed in prostate cancer. The purpose of this study was to test the feasibility of using the levels of trefoil factors as a plasma marker for prostate cancer....

  4. Cost-efficacy analysis of hormonal treatments for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Sergio Iannazzo

    2008-09-01

    Full Text Available Introduction: prostatic cancer is the second more frequent cancer in Italy (after lung cancer and is the third cancer-related death cause. Age is the principal risk factor and, given the ageing process undergoing in the Italian population, it seems clear that the public sanitary expenditure to treat the disease is bound to increase, arising the need to perform pharmacoeconomic evaluations of the therapeutic strategies available. Methods: we performed a cost/utility analysis, through a Markov model, of several hormonal therapies in patients with advanced prostate cancer who underwent radical prostatectomy, from the biochemical recurrence to death. Nine androgen suppression therapies were considered: orchiectomy, two nonsteroidal antiandrogens (NSAA, four luteinizing hormone-releasing hormone (LHRH agonists, cyproterone acetate and the association of a NSAA and a LHRH (BAT. In the simulation the androgen suppression therapies were started at the PSA recurrence and never stopped until death. The model used the Italian NHS prospective and a time horizon corresponding to patient’s lifetime. Drug costs were calculated for each therapy, considering the less costly brand. Results: all the considered therapies produced a life expectancy (LE of about 12 life years (LYs with a small variability ranging from 12.3 LYs for BAT (the most effective to 11.37 LYs for NSAA-flutamide (the least effective. Quality adjusted life expectancy ranged from 9.98 QALYs for BAT to 9.28 QALYs for NSAA-flutamide. The average cost per patient presented a more enhanced variability, from 12,538 Euro for orchiectomy to 59,496 Euro for NSAA-bicalutamide. Among all the alternatives orchiectomy resulted the most cost/effective alternative with a cost/utility ratio of about 1,300 Euro/QALY. In the LHRH-agonists class leuprorelin was the most cost/effective with about 2,200 Euro/QALY. A one-way sensitivity analysis showed a substantial stability of the results. Conclusions: BAT

  5. Organoid culture systems for prostate epithelial and cancer tissue.

    Science.gov (United States)

    Drost, Jarno; Karthaus, Wouter R; Gao, Dong; Driehuis, Else; Sawyers, Charles L; Chen, Yu; Clevers, Hans

    2016-02-01

    This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material contain the differentiated luminal and basal cell types, whereas organoids derived from prostate cancer tissue mimic the histology of the tumor. We explain how to establish these cultures in the fully defined serum-free conditioned medium that is required to sustain organoid growth. Starting with the plating of digested tissue material, full-grown organoids can usually be obtained in ∼2 weeks. The culture protocol we describe here is currently the only one that allows the growth of both the luminal and basal prostatic epithelial lineages, as well as the growth of advanced prostate cancers. Organoids established using this protocol can be used to study many different aspects of prostate biology, including homeostasis, tumorigenesis and drug discovery.

  6. Early Growth Inhibition Is Followed by Increased Metastatic Disease with Vitamin D (Calcitriol) Treatment in the TRAMP Model of Prostate Cancer

    Science.gov (United States)

    Karasik, Ellen; Gillard, Bryan; Moser, Michael T.; Johnson, Candace S.; Trump, Donald L.; Foster, Barbara A.

    2014-01-01

    The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (calcitriol) has antiproliferative effects in non-aggressive prostate cancer, however, its effects in more aggressive model systems are still unclear. In these studies, effects of calcitriol and a less-calcemic vitamin D analog, QW-1624F2-2 (QW), were tested in vivo, using the aggressive autochthonous transgenic adenocarcinoma of mouse prostate (TRAMP) model. To study prevention of androgen-stimulated prostate cancer, vehicle, calcitriol (20 µg/kg), or QW (50 µg/kg) were administered to 4 week-old TRAMP mice intraperitoneal (i.p.) 3×/week on a MWF schedule for 14 weeks. Calcitriol and QW slowed progression of prostate cancer as indicated by reduced urogenital tract (p = 0.0022, calcitriol; p = 0.0009, QW) and prostate weights (p = 0.0178, calcitriol; p = 0.0086, QW). However, only calcitriol increased expression of the pro-differentiation marker, cadherin 1 (p = 0.0086), and reduced tumor proliferation (p = 0.0467). By contrast, neither vitamin D analog had any effect on castration resistant prostate cancer in mice treated pre- or post-castration. Interestingly, although vitamin D showed inhibitory activity against primary tumors in hormone-intact mice, distant organ metastases seemed to be enhanced following treatment (p = 0.0823). Therefore, TRAMP mice were treated long-term with calcitriol to further examine effects on metastasis. Calcitriol significantly increased the number of distant organ metastases when mice were treated from 4 weeks-of-age until development of palpable tumors (20–25 weeks-of-age)(p = 0.0003). Overall, data suggest that early intervention with vitamin D in TRAMP slowed androgen-stimulated tumor progression, but prolonged treatment resulted in development of a resistant and more aggressive disease associated with increased distant organ metastasis. PMID:24586868

  7. Early growth inhibition is followed by increased metastatic disease with vitamin D (calcitriol treatment in the TRAMP model of prostate cancer.

    Directory of Open Access Journals (Sweden)

    Adebusola Alagbala Ajibade

    Full Text Available The active metabolite of vitamin D3, 1,25-dihydroxyvitamin D3 (calcitriol has antiproliferative effects in non-aggressive prostate cancer, however, its effects in more aggressive model systems are still unclear. In these studies, effects of calcitriol and a less-calcemic vitamin D analog, QW-1624F2-2 (QW, were tested in vivo, using the aggressive autochthonous transgenic adenocarcinoma of mouse prostate (TRAMP model. To study prevention of androgen-stimulated prostate cancer, vehicle, calcitriol (20 µg/kg, or QW (50 µg/kg were administered to 4 week-old TRAMP mice intraperitoneal (i.p. 3×/week on a MWF schedule for 14 weeks. Calcitriol and QW slowed progression of prostate cancer as indicated by reduced urogenital tract (p = 0.0022, calcitriol; p = 0.0009, QW and prostate weights (p = 0.0178, calcitriol; p = 0.0086, QW. However, only calcitriol increased expression of the pro-differentiation marker, cadherin 1 (p = 0.0086, and reduced tumor proliferation (p = 0.0467. By contrast, neither vitamin D analog had any effect on castration resistant prostate cancer in mice treated pre- or post-castration. Interestingly, although vitamin D showed inhibitory activity against primary tumors in hormone-intact mice, distant organ metastases seemed to be enhanced following treatment (p = 0.0823. Therefore, TRAMP mice were treated long-term with calcitriol to further examine effects on metastasis. Calcitriol significantly increased the number of distant organ metastases when mice were treated from 4 weeks-of-age until development of palpable tumors (20-25 weeks-of-age(p = 0.0003. Overall, data suggest that early intervention with vitamin D in TRAMP slowed androgen-stimulated tumor progression, but prolonged treatment resulted in development of a resistant and more aggressive disease associated with increased distant organ metastasis.

  8. PSA Response to Lenalidomide Therapy in a Pre-Treated Patient with Metastatic Prostate Cancer Refractory to Hormones and Chemotherapy: A Case Report

    Directory of Open Access Journals (Sweden)

    Joan Manel Gasent Blesa

    2012-04-01

    Full Text Available Hormone-resistant prostate cancer (HRPC occurs when prostate cancer is no longer responsive to hormone therapy. Treatment options are limited, and there is a clear necessity for therapies that improve outcome. Preclinical and clinical evidence supports the role of the immunomodulatory agent lenalidomide in HRPC. In this paper, we report that lenalidomide showed antitumoral activity in a patient with HRPC and bone metastases pre-treated with chemotherapy, decreased the PSA level and improved the patient’s health status for the first 5 months. It is important to emphasize that it was not associated with hematologic toxicity.

  9. ABO Blood Group Alleles and Prostate Cancer Risk: Results from the Breast and Prostate Cancer Cohort Consortium (BPC3)

    Science.gov (United States)

    Markt, Sarah C.; Shui, Irene M.; Unger, Robert H.; Urun, Yuksel; Berg, Christine D.; Black, Amanda; Brennan, Paul; Bueno-de-Mesquita, H. Bas; Gapstur, Susan M.; Giovannucci, Edward; Haiman, Christopher; Henderson, Brian; Hoover, Robert N.; Hunter, David J.; Key, Timothy J.; Khaw, Kay-Tee; Canzian, Federico; Larranga, Nerea; Le Marchand, Loic; Ma, Jing; Naccarati, Alessio; Siddiq, Afshan; Stampfer, Meir J.; Stattin, Par; Stevens, Victoria L.; Stram, Daniel O.; Tjønneland, Anne; Travis, Ruth C.; Trichopoulos, Dimitrios; Ziegler, Regina G.; Lindstrom, Sara; Kraft, Peter; Mucci, Lorelei A.; Choueiri, Toni K.; Wilson, Kathryn M.

    2015-01-01

    Background ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney and skin, but has not been evaluated in relation to risk of aggressive prostate cancer. Methods We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype and risk of aggressive prostate cancer (Gleason score ≥8 or locally advanced/metastatic disease (stage T3/T4/N1/M1). Results We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR=0.97, 95% CI=0.87-1.08; Type B: OR=0.92, 95% CI=0.77-1.09; Type AB: OR=1.25, 95% CI=0.98-1.59, compared to Type O, respectively). Similarly, there was no association between ‘dose’ of A or B alleles and aggressive prostate cancer risk. Conclusions ABO blood type was not associated with risk of aggressive prostate cancer. PMID:26268879

  10. The increased accumulation of [{sup 18}F]fluorodeoxyglucose in untreated prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Oyama, Nobuyuki; Akino, Hironobu; Suzuki, Yuji; Kanamaru, Hiroshi; Okada, Kenichiro [Fukui Medical Univ., Matsuoka (Japan); Sadato, Norihiro; Yonekura, Yoshiharu

    1999-12-01

    To evaluate the clinical usefulness of [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) compared with histopathological grading, clinical stage and serum prostatic specific antigen (PSA) level in the detection and characterization of prostate cancer. Forty-four patients with histologically proven prostate cancer and five control subjects with benign prostatic hyperplasia (BPH) were prospectively investigated with FDG-PET prior to treatment. By visual inspection, FDG accumulation was positive in 28 patients with prostate cancer (sensitivity 64%), whereas all were negative in the control group. FDG-PET in three patients with lymph node metastases did not show any high intrapelvic accumulations corresponding to metastatic sites. Among 12 patients with multiple bone metastases which were detected with 99m-HMDP bone scintigraphy, nine (75%) showed moderate to high FDG accumulation at the sites of bone metastases. Quantitatively, FDG accumulation in prostate cancer was significantly higher than in BPH and there was a tendency for FDG uptake of tumors to be higher with higher histological Gleason grades. Furthermore, FDG uptake in tumors with lymph node and/or bone metastasis was significantly higher than that of localized stages. However, the correlation between PSA and FDG uptake in the prostate cancer was very weak for clinical relevance. Although FDG-PET was not sensitive enough to detect prostate cancer in clinical use, it is suggested that glucose metabolism in prostate cancer tended to be higher in patients with tumors of advanced stages. (author)

  11. Which is the best advanced MR imaging protocol for predicting recurrent metastatic brain tumor following gamma-knife radiosurgery: focused on perfusion method

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Myeong Ju; Kim, Ho Sung; Choi, Choong Gon; Kim, Sang Joon [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Songpa-Gu, Seoul (Korea, Republic of)

    2015-04-01

    High spatial resolution of dynamic contrast-enhanced (DCE) MR imaging allows characterization of heterogenous tumor microenvironment. Our purpose was to determine which is the best advanced MR imaging protocol, focused on additional MR perfusion method, for predicting recurrent metastatic brain tumor following gamma-knife radiosurgery (GKRS). Seventy-two consecutive patients with post-GKRS metastatic brain tumor were enrolled. Two readers independently calculated the percentile histogram cutoffs for normalized cerebral blood volume (nCBV) from dynamic susceptibility contrast (DSC) imaging and initial area under the time signal-intensity curve (IAUC) from DCE imaging, respectively. Area under the receiver operating characteristic curve (AUC) and interreader agreement were assessed. For differentiating tumor recurrence from therapy effect, adding DCE imaging to diffusion-weighted imaging (DWI) significantly improved AUC from 0.79 to 0.95 for reader 1 and from 0.80 to 0.96 for reader 2, respectively. There was no significant difference of AUC between the combination of DWI with DSC imaging and the combination of DWI with DCE imaging for both readers. With the combination of DWI and DCE imaging, the sensitivity and specificity were 86.7 and 88.1 % for reader 1 and 90.0 and 85.7 % for reader 2, respectively. The intraclass correlation coefficient (ICC) between readers was highest for calculation of the 90th percentile histogram cutoffs for IAUC (ICC, 0.87). Adding perfusion MR imaging to DWI significantly improves the prediction of recurrent metastatic tumor; however, the diagnostic performance is not affected by selection of either DSC or DCE MR perfusion method. (orig.)

  12. Predictors of Chemotherapy-Induced Toxicity and Treatment Outcomes in Elderly Versus Younger Patients With Metastatic Castration-Resistant Prostate Cancer

    DEFF Research Database (Denmark)

    Kongsted, Per; Svane, Inge Marie; Lindberg, Henriette;

    2016-01-01

    records from 421 consecutive patients treated with first-line docetaxel (75 mg/m(2) every 3 weeks) and low-dose prednisolone from 2007 to 2013 at Herlev University Hospital were reviewed. Common Terminology Criteria for Adverse Events, version 4.0, and the Prostate Cancer Working Group 2 guidelines were...

  13. Is whole gland salvage cryotherapy effective as palliative treatment of haematuria in patients with locally advanced prostate cancer? Results of a preliminary case series

    Science.gov (United States)

    Mucciardi, Giuseppe; Galì, Alessandro; Pappalardo, Rosa; Lembo, Francesco; Anastasi, Giuseppina; Butticè, Salvatore; Ascenti, Giorgio; Lugnani, Franco

    2015-01-01

    Objectives: Locally advanced prostate cancer may cause several complications such as haematuria, bladder outlet obstruction, and renal failure due to the ureteral obstruction. Various treatments have been suggested, including radiotherapy, antifibrinolytics, bladder irrigation with alum solution, transurethral surgery and angioembolization, none of which have proven effectiveness. In the last years cryoablation has become a valid therapeutic option for prostate cancer. In our experience we used this ‘new’ technique as haemostatic therapy. Methods: We selected four patients with gross haematuria affected by locally advanced hormone refractory prostate cancer, who had already been treated with primary radiotherapy. We used third-generation cryotherapy: under ultrasonographic guidance, we inserted six cryoprobes, two in each of the vascular pedicles reaching at least −60°C, and three thermometers. We then induced two freeze–thaw cycles. Results: After the operation the haematuria stopped in all patients and at 9-month follow up we observed a mean of four red cells (range three to five) in the urinary sediment with no evidence of bacteriuria. Prostate volume, prostate-specific antigen and postmicturition residue were significantly reduced. Qmax improved significantly too. Conclusion: Our experience has given us good results with minimal intra- and postoperative complications. We think that haemostatic cryotherapy as a palliative approach for locally advanced prostate cancer could represent a valid treatment option and more consideration could be given to its use. PMID:26425138

  14. Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

    Directory of Open Access Journals (Sweden)

    Xiaohui Zeng

    Full Text Available BACKGROUND: Maintenance gefitinib significantly prolonged progression-free survival (PFS compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC after four chemotherapeutic cycles (21 days per cycle of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. METHODS AND FINDINGS: A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP threshold of $16,349 (3 × per-capita gross domestic product of China. The sensitivity analyses all suggested that the model was robust. CONCLUSIONS: Maintenance gefitinib

  15. Prostate; Prostate

    Energy Technology Data Exchange (ETDEWEB)

    Rouviere, O.; Valette, O.; Grivolat, S.; Colin-Pangaud, C.; Bouvier, R.; Chapelon, J.Y.; Gelet, A.; Lyonnet, D.; Rouviere, O.; Mege-Lechevallier, F.; Chapelon, J.Y.; Gelet, A.; Bouvier, R.; Boutitie, F.; Lyonnet, D. [69 - Lyon (France)

    2005-10-15

    Two methods to detect recurrence of prostate cancer are presented. Dynamic magnetic resonance imaging after radiotherapy and color doppler after high intensity focused ultrasounds (but with patients that have not received a hormones therapy). These two methods presents an useful contribution. (N.C.)

  16. A genetic polymorphism of the osteoprotegerin gene is associated with an increased risk of advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Horikawa Yohei

    2008-08-01

    Full Text Available Abstract Background The purpose of this study was to evaluate the role of osteoprotegerin gene (OPG polymorphisms as genetic modifiers in the etiology of prostate cancer (PCa and disease progression. Methods Three hundred and sixty one patients with PCa and 195 normal controls were enrolled in the study, and two genetic polymorphisms, 149 T/C and 950 T/C in the putative promoter region of OPG, were genotyped. Results There was no significant difference in the genotype frequencies between PCa patients and controls (P = 0.939 and 0.294 for 149 T/C and 950 T/C polymorphisms, respectively. However, those patients with TC and TT genotypes in the 950 T/C polymorphism had a significantly increased risk of extraprostatic (age-adjusted odds ratio; aOR = 1.74 and 2.03 for TC and TT genotypes compared with the CC genotype, P = 0.028 and metastatic disease (aOR = 1.72 and 2.76 for TC and TT genotypes compared with the CC genotype, P = 0.009 compared with those with the CC genotype. In addition, analysis of the metastatic PCa patients (Stage D showed that the presence of the T allele of the OPG 950 T/C polymorphism was an independent risk factor predicting survival by Cox proportional hazard regression analyses (P = 0.031. Conclusion Progression of PCa may be influenced by an intrinsic genetic factor of the host's bone metabolism. The variant C allele of 950 T/C in the OPG promoter may play a major role as a genetic safe guard against progression in patients with PCa.

  17. Management of advanced prostate cancer Tratamento do câncer de próstata avançado

    Directory of Open Access Journals (Sweden)

    Rafael A. Kaliks

    2008-04-01

    Full Text Available Geriatricians and general practitioners often follow patients with metastatic prostate cancer. The epidemiology and basic treatment principles of metastatic prostate cancer are discussed aiming to update the topic for the non-oncologist. Hormone manipulation remains the basis of treatment, usually up to a second line of therapy. Selected cases are treated successfully with intermittent androgen ablation. When new hormone-independent clones arise, chemotherapy should be added to therapy that confers improved survival as well as better quality of life when based on taxanes. In specific situations, additional measures such as bisphosphonates and radiation therapy should be included in the treatment. As a rule, the public health system makes available the necessary medication to ensure treatment for the vast majority of patients in Brazil.Pacientes com câncer de prostata metastático estão freqüentemente sob os cuidados de geriatras e clínicos gerais. Discutimos a epidemiologia e os princípios básicos do tratamento do câncer de próstata metastático, visando atualizar o não-oncologista no assunto. A base do tratamento continua sendo a manipulação hormonal, inclusive como tratamento de segunda linha. Casos selecionados podem ser tratados com ablação androgênica intermitente de maneira eficaz. Quando se desenvolvem clones de células hormônio-independentes, quimioterápicos são incorporados na terapia. A quimioterapia confere não só benefício em sobrevida, mas também na qualidade de vida, quando baseado em taxanos. Medidas adicionais como o uso de bisfosfonados e radioterapia devem ser incorporadas no tratamento em situações especiais. De modo geral, o sistema público de saúde do Brasil disponibiliza todas as medicações necessárias ao adequado tratamento dos pacientes no país.

  18. Expression of Ki-67 (MIB-1) and GLUT-1 proteins in non-advanced prostatic cancer.

    Science.gov (United States)

    Luczynska, Elzbieta; Gasinska, Anna; Wilk, Waclaw

    2012-12-01

    The expression of Ki-67 (MIB-1) and glucose transporter-1 (GLUT-1) were evaluated in patients with clinically localized prostate cancer (PC) who had undergone radical prostatectomy with curative intent. 140 low advanced PC specimens were studied. Protein expression was assessed immunohistochemically on tumour sections and expressed as a labelling index, i.e. the percentage of positively stained cells. In the case of Ki-67 nuclear staining and in the case of GLUT-1 membrane and cytoplasmic staining was considered as positive. The patients' mean age was 62.9 ±6.2 years. There were 13 (9.3%) at pTNM stage 1, 78 (55.7%) at stage 2, 40 (28.6%) at stage 3 and 9 (6.4%) at stage 4, respectively. 75 (53.6%) tumours were well differentiated (Gleason score ≤6), 52 (37.1%) moderately differentiated (Gleason score of 7) and 13 (9.3%) poorly differentiated (Gleason score 8-10). The mean pre-operative serum PSA was 9.9 ± SE 0.5 ng/ml, and the mean LI was equal to 8.1 ±0.6% and 29.7 ±2.0%, for MIB-1 and GLUT-1, respectively. Increase of pathological tumor volume and tumor grade was associated with statistically significant growth of PSA (p GLUT-1 LI the relation was not significant. Ki-67 expression was correlated with PSA levels (p = 0.013) and GLUT-1 scores (p = 0.04). In PC, an increase in the proliferation rate (higher MIB-1LI) in higher pTNM stages and tumour grades may point to Ki-67 as a good marker of biological aggressiveness useful in selecting patients for more aggressive treatment. A correlation between proliferation and GLUT-1 score may be the evidence of active glycolytic metabolism in hypoxic regions.

  19. Outcomes of locally advanced prostate cancer: a single institution study of 209 patients in Japan

    Institute of Scientific and Technical Information of China (English)

    Toshihiro Saito; Yasuo Kitamura; Shuichi Komatsubara; Yasuo Matsumoto; Tadashi Sugita; Noboru Hara

    2006-01-01

    Aim: To investigate the outcomes for Asian populations with locally advanced/clinical stage Ⅲ prostate cancer (Pca)treated with currently prevailing modalities. Methods: We reviewed the record of 209 patients with clinical stage Ⅲ Pca, who were treated at Niigata Cancer Center Hospital between 1992 and 2003. Treatment options included hormone therapy-combined radical prostatectomy (RP+HT), hormone therapy-combined external beam irradiation (EBRT+HT) and primary hormone therapy (PHT). Results: The 5- and 10-year overall survival rates were 80.3%and 46.1% in all cohorts, respectively. The survival rates were 87.3% and 66.5% in the RP+HT group, 94.9% and 70.0% in the EBRT+HT group and 66.1% and 17.2% in the PHT group, respectively. A significant survival advantage was found in the EBRT+HT group compared with that in the PHT group (P < 0.0001). Also, the RP+HT group had better survival than the PHT group (P = 0.0107). The 5- and 10-year disease-specific survival rates for all cases were 92.5% and 80.0%, respectively. They were 93.8% and 71.4% in the RP+HT group, 96.6% and 93.6% in the EBRT+HT group and 88.6% and 62.3% in the PHT group, respectively. A survival advantage was found in the EBRT+HT group compared with the PHT group (P = 0.029). No significant difference was found in disease-specific survival between the EBRT+HT and RP+HT groups or between the RP+HT and PHT groups. Conclusion: Although our findings indicate that radiotherapy plus HT has a survival advantage in this stage of Pca, we recommend therapies that take into account the patients' social and medical conditions for Asian men with clinical stage Ⅲ PCa.

  20. Effect of Intermittent Androgen Blockade on the Quality of Life of Patients with Advanced Prostate Carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    OBJECTIVE To investigate the effect of intermittent androgen blockade (IAB) on the quality of life (QOL) of patients with advanced prostatic carcinoma (APC).METHODS Investigations on the QOL of 51 APC patients receiving IAB treatment, totaling 3 times, i.e. 6 months before and after, and 12 months after treatment, were perform using the EORTC QLQ-C30 measuring scale and QLQ-PR25 scale.RESULTS Although IAB became an economic burden for the families, it was lessened during the intermission (P<0.05). The overall health status significantly improved 6 months after IAB treatment (P<0.01), especially during the intermission (P<0.05), with a total or local easement of pain (P<0.01) and an improvement of urinary function (P<0.01). Although there was impairment,to various degrees, in many functions of the patients on the 6th month of treatment, such as the physical function (P<0.05), role function (P<0.05), the emotional (P<0.01) and the social functions (P<0.01), with an enhancement of fatigue (P<0.01), these functions gradually recovered by the 12th month as the intermission started. Treatment-related symptoms such as flushing and mammary swelling significantly emerged on the 6th treatment month (P<0.01), and lessened on the 12th (P<0.01). During the treatment period,therewas an notable drop in sexual interest (P<0.01), with a deprivation of sex life, but revived to various degrees during the intermission (P<0.01).CONCLUSION Although IAB treatment of APC patients did impair the physiologic and psychologic status of patients to varying degrees, these were improved and restored during the intermission.

  1. Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

    Science.gov (United States)

    2015-10-01

    2) Assess the efficacy of company material on the growth of prostate cancer PDX in bone of male SCID mice. 3) Screen tissue microarrays...responder ID profiles will be assessed in clinical trials. Bone metastases, targeted therapy, prostate cancer 5 Specific Aim 2: Develop a responder...described in A (*P < 0.007). 9 from MDA PCa 118b PDX growing in the bone of male SCID mice and treated with NVP-BGJ398 and JNJS 42756493 indicated

  2. Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    A. I. Neimark

    2014-01-01

    Full Text Available Objective: to evaluate the efficiency and safety of using the luteinizing hormone releasing hormone leuprorelin with the Atrigel delivery system in doses of 7.5, 22.5, and 45 mg as an adjuvant regimen in high- and moderate-risk cancer patients who have received high-intensity focused ultrasound (HIFU therapy.Subjects and methods. Moderate- and high-risk locally advanced prostate cancer (PC patients treated with HIFU (n = 28 and HIFU in combination with hormone therapy during 6 months (n = 31 were examined.Results. The investigation has shown that leuprorelin acetate monotherapy used within 6 months after HIFU therapy can achieve the highest reduction in prostate-specific antigen levels and positively affect the symptoms of the disease. HIFU in combination with androgen deprivation substantially diminishes the clinical manifestations of the disease and improves quality of life in HIFU-treated patients with PC, by reducing the degree of infravesical obstruction (according to uroflowmetric findings and IPSS scores, and causes a decrease in prostate volume as compared to those who have undergone HIFU only. Treatment with leuprorelin having the Atrigel delivery system has demonstrated the low incidence of adverse reactions and good tolerability.

  3. Results from a Phase I Study of Lapatinib with Gemcitabine and Cisplatin in Advanced or Metastatic Bladder Cancer: EORTC Trial 30061

    DEFF Research Database (Denmark)

    Cerbone, Linda; Sternberg, Cora N; Sengeløv, Lisa;

    2016-01-01

    BACKGROUND/OBJECTIVE: Lapatinib is a potent HER1 and HER2 inhibitor. Gemcitabine-cisplatin (GC) is a standard chemotherapy regimen for advanced/metastatic bladder cancer. This phase I study examined the safety of lapatinib in combination with GC in patients with bladder cancer. The primary aim...... was to determine the maximum tolerated dose (MTD) of lapatinib in combination with GC. METHODS: A 3 + 3 dose escalation protocol was used with lapatinib at 750, 1,000 and then 1,250 mg. It was dosed daily with gemcitabine (1,000 mg/m2 on days 1, 8 and 15) and cisplatin (70 mg/m2 on day 2) every 28 days. In all, 18...

  4. Regorafenib: A novel tyrosine kinase inhibitor: A brief review of its therapeutic potential in the treatment of metastatic colorectal carcinoma and advanced gastrointestinal stromal tumors

    Directory of Open Access Journals (Sweden)

    P Thangaraju

    2015-01-01

    Full Text Available Regorafenib is a novel oral multitargeted tyrosine kinase inhibitor having both antitumor and anti-angiogenic activities. Regorafenib was recently approved by US Food and Drug Administration in February 25, 2013 in the treatment for patients with advanced gastrointestinal stromal tumor and for the treatment of patients with metastatic colorectal carcinoma after disease progression or intolerance to imatinib mesylate and sunitinib therapy. Oral regorafenib demonstrates a high level of efficacy with acceptable tolerability with the 160 mg daily for 3 weeks followed by 1 week off schedule; a continuous schedule could be of interest. Hypertension, mucositis, hand foot skin reaction, diarrhea and asthenia are the most common side-effects. Regardless of these encouraging results, studies investigating, adjuvant and neoadjuvant settings are awaited, as well as trials using regorafenib in combination with chemotherapy or other targeted therapies. Clinical trials investigating regorafenib in other tumor types are ongoing.

  5. Changes in and Associations Among Functional Status and Perceived Quality of Life of Patients With Metastatic/Locally Advanced Cancer Receiving Rehabilitation for General Disability.

    Science.gov (United States)

    Sekine, Ryuichi; Ogata, Masami; Uchiyama, Ikuyo; Miyakoshi, Koichi; Uruma, Megumi; Miyashita, Mitsunori; Morita, Tatsuya

    2015-11-01

    The primary aims were to clarify the changes in the functional status and quality of life of patients with metastatic/locally advanced cancer who received rehabilitation therapy. This is a cohort study, and all consecutive patients who received rehabilitation therapy were evaluated before and 2 weeks after. Outcome measures were the Functional Independence Measure (FIM), perceived independence, and overall quality of life (European Organization for Research and Treatment of Cancer C30). A total of 128 patients were included. Although the FIM score significantly decreased, the overall quality of life significantly increased. Even in the patients with deteriorated FIM scores, the overall quality of life was maintained despite a significantly decreased perceived independence. Terminally ill patients with cancer who received a rehabilitation program maintained their overall quality of life despite an objective decline in the physical functional status.

  6. Pemetrexed combined with paclitaxel in patients with advanced or metastatic non-small-cell lung cancer: a phase I-II trial.

    Science.gov (United States)

    Stathopoulos, George P; Dimitroulis, John; Toubis, Michael; Katis, Costas; Karaindros, Dimitris; Stathopoulos, John; Koutandos, John

    2007-07-01

    Pemetrexed, a novel multi-targeted agent established for the treatment of mesothelioma, has been under investigation for other malignancies, and in recent years particularly for non-small-cell lung cancer (NSCLC). In the present trial we investigated pemetrexed in combination with paclitaxel as front-line treatment in advanced or metastatic NSCLC. Our objectives were to determine the response rate, median and overall survival and toxicity. From April 2005 until May 2006, 51 patients with advanced or metastatic NSCLC were enrolled and 48 were considered evaluable. There were 39 males and nine females, median age 62 years (range 37-81 years), one patient stage IIIA N(2), 23 patients, IIIB and 24, stage IV. All patients had a cytologically- or histologically-confirmed diagnosis. Pemetrexed was administered at a standard dose of 500mg/m(2) and paclitaxel at an escalating dose starting at 135mg/m(2), then 150mg/m(2) and ending at a dose of 175mg/m(2); the level was increased every three patients. Both agents were administered on day 1, repeated every 3 weeks for six courses. A 39.6% partial response rate was observed with a median survival of 14 months. Toxicity was mild with 8.3% grade 3 and 4 neutropenia and other very mild hematologic and non-hematologic adverse reactions. The combination of pemetrexed and paclitaxel at doses of 500mg/m(2) and 175mg/m(2), respectively, has been shown to be an effective combination with very limited toxicity.

  7. A phase I study of combined docetaxel and repeated high activity {sup 186}Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

    Energy Technology Data Exchange (ETDEWEB)

    Dodewaard-de Jong, Joyce M. van; Bloemendal, Haiko J. [Meander Medical Centre, Department of Internal Medicine, Amersfoort (Netherlands); Klerk, John M.H. de; Haas, Marie J. de [Meander Medical Centre, Department of Nuclear Medicine, Amersfoort (Netherlands); Bezooijen, Bart P.J. van [Meander Medical Centre, Department of Urology, Amersfoort (Netherlands); Wilson, Richard H.; O' Sullivan, Joe M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast, N. Ireland (United Kingdom)

    2011-11-15

    Bone-seeking radiopharmaceuticals have palliative benefit in castration-resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown improvement of survival and quality of life when radiopharmaceuticals were given repeatedly or in combination with chemotherapy. We designed a phase I study combining docetaxel and {sup 186}Re-labelled hydroxyethylidene diphosphonate (HEDP) in men with CRPC and bone metastases to evaluate toxicity. A dose escalation schedule was designed consisting of four dose levels with a standard dosage of docetaxel (75 mg/m{sup 2} 3-weekly). {sup 186}Re-HEDP was given in increasing activities (1,250 MBq up to 2,500 MBq) after the third and sixth cycle of docetaxel. Dose limiting toxicity (DLT) was defined as any grade 4 toxicity lasting more than 7 days or any grade 3 toxicity that did not recover within 10 days. Three patients were planned for each dose level expanding to six if a DLT occurred. Fourteen patients were recruited with a median age of 64.6 years. One DLT, grade 3 thrombocytopenia lasting >10 days, occurred at dose level 3 leading to expansion of this group to six. One of these patients had an episode of acute renal failure which resolved. Because of production problems of {sup 186}Re-HEDP dose level 4 was not started. Combined therapy with docetaxel and {sup 186}Re-HEDP is generally well tolerated in patients with CRPC metastatic to bone. We will conduct a randomized phase II study using three cycles of docetaxel 75 mg/m{sup 2} 3-weekly followed by {sup 188}Re-HEDP 40 MBq/kg body weight, followed by another three cycles of docetaxel 75 mg/m{sup 2}, followed by {sup 188}Re-HEDP 20 MBq/kg body weight. (orig.)

  8. A phase 2 study of high-activity {sup 186}Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone

    Energy Technology Data Exchange (ETDEWEB)

    O' Sullivan, J.M. [Queen' s University Belfast/Belfast City Hospital, Department of Oncology, Belfast (United Kingdom); Norman, A.R. [Royal Marsden Foundation NHS Trust, Department of Computing, Sutton, Surrey (United Kingdom); McCready, V.R.; Flux, G.; Buffa, F.M. [Royal Marsden Foundation NHS Trust, Department of Physics, Sutton, Surrey (United Kingdom); Johnson, B. [Royal Marsden Foundation NHS Trust, Bob Champion Unit, Sutton, Surrey (United Kingdom); Coffey, J.; Horwich, A.; Huddart, R.A.; Parker, C.C.; Dearnaley, D.P. [Royal Marsden Foundation NHS Trust, Academic Unit of Urology, Sutton, Surrey (United Kingdom); Cook, G. [Royal Marsden Foundation NHS Trust, Department of Nuclear Medicine, Sutton, Surrey (United Kingdom); Treleaven, J. [Royal Marsden Foundation NHS Trust, Department of Haematology, Sutton, Surrey (United Kingdom)

    2006-09-15

    We investigated the potential for improvement in disease control by use of autologous peripheral blood stem cell transplant (PBSCT) to permit administration of high activities of {sup 186}Re-hydroxyethylidene diphosphonate (HEDP) in patients with progressive hormone-refractory prostate cancer (HRPC). Eligible patients had progressive HRPC metastatic to bone, good performance status and minimal soft tissue disease. Patients received 5,000 MBq of {sup 186}Re-HEDP i.v., followed 14 days later by PBSCT. Response was assessed using PSA, survival, pain scores and quality of life. Thirty-eight patients with a median age of 67 years (range 50-77) and a median PSA of 57 ng/ml (range 4-3,628) received a median activity of 4,978 MBq {sup 186}Re-HEDP (range 4,770-5,100 MBq). The most serious toxicity was short-lived grade 3 thrombocytopenia in 8 (21%) patients. The median survival of the group is 21 months (95%CI 18-24 months) with Kaplan-Meier estimated 1- and 2-year survival rates of 83% and 40% respectively. Thirty-one patients (81%, 95% CI 66-90%) had stable or reduced PSA levels 3 months post therapy while 11 (29%, 95% CI 15-49%) had PSA reductions of >50% lasting >4 weeks. Quality of life measures were stable or improved in 27 (66%) at 3 months. We have shown that it is feasible and safe to deliver high-activity radioisotope therapy with PBSCT to men with metastatic HRPC. Response rates and survival data are encouraging; however, further research is needed to define optimal role of this treatment approach. (orig.)

  9. Gene therapy for prostate cancer.

    LENUS (Irish Health Repository)

    Tangney, Mark

    2012-01-31

    Cancer remains a leading cause of morbidity and mortality. Despite advances in understanding, detection, and treatment, it accounts for almost one-fourth of all deaths per year in Western countries. Prostate cancer is currently the most commonly diagnosed noncutaneous cancer in men in Europe and the United States, accounting for 15% of all cancers in men. As life expectancy of individuals increases, it is expected that there will also be an increase in the incidence and mortality of prostate cancer. Prostate cancer may be inoperable at initial presentation, unresponsive to chemotherapy and radiotherapy, or recur following appropriate treatment. At the time of presentation, patients may already have metastases in their tissues. Preventing tumor recurrence requires systemic therapy; however, current modalities are limited by toxicity or lack of efficacy. For patients with such metastatic cancers, the development of alternative therapies is essential. Gene therapy is a realistic prospect for the treatment of prostate and other cancers, and involves the delivery of genetic information to the patient to facilitate the production of therapeutic proteins. Therapeutics can act directly (eg, by inducing tumor cells to produce cytotoxic agents) or indirectly by upregulating the immune system to efficiently target tumor cells or by destroying the tumor\\'s vasculature. However, technological difficulties must be addressed before an efficient and safe gene medicine is achieved (primarily by developing a means of delivering genes to the target cells or tissue safely and efficiently). A wealth of research has been carried out over the past 20 years, involving various strategies for the treatment of prostate cancer at preclinical and clinical trial levels. The therapeutic efficacy observed with many of these approaches in patients indicates that these treatment modalities will serve as an important component of urological malignancy treatment in the clinic, either in isolation or

  10. A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate

    DEFF Research Database (Denmark)

    Iversen, P; Christensen, M G; Friis, E;

    1990-01-01

    In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor of the co......In a multicenter Phase III trial 264 patients with advanced prostatic cancer were randomized to either bilateral orchiectomy or treatment with zoladex supplemented by flutamide. Presently, median follow-up time is 30 months. A small difference in objective response was recorded in favor...... of the combination therapy, whereas no statistically significant difference was found in subjective response to therapy, time to progression, and overall survival. Adverse effects were more commonly encountered in the pharmacologically treated patients. It is concluded that the combination of zoladex plus flutamide...... is not clinically superior to orchiectomy in the treatment of patients with advanced carcinoma of the prostate....

  11. A Single-arm, Multicenter, Open-label Phase 2 Study of Lapatinib as the Second-line Treatment of Patients With Locally Advanced or Metastatic Transitional Cell Carcinoma

    NARCIS (Netherlands)

    C. Wülfing; J.P.H. Machiels; D.J. Richel; M.O. Grimm; U. Treiber; M.R. de Groot; P. Beuzeboc; R. Parikh; F. Pétavy; I.A. El-Hariry

    2009-01-01

    BACKGROUND: The treatment of recurrent transitional cell carcinoma (TCC) remains an unmet clinical need. This study assessed lapatinib, a dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and HER-2, as second-line therapy in patients with locally advanced or metastatic TCC. M

  12. Perspectives on sipuleucel-T: Its role in the prostate cancer treatment paradigm

    OpenAIRE

    Gulley, James L.; Mulders, Peter; Albers, Peter; Banchereau, Jacques; Bolla, Michel; Pantel, Klaus; Powles, Thomas

    2015-01-01

    ABSTRACT Sipuleucel-T is an autologous cellular immunotherapy approved in the US for patients with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). This significant advance for mCRPC treatment provides healthcare professionals with another effective therapy to extend survival. As an immunotherapy, sipuleucel-T possesses specific characteristics differentiating it from traditional therapies. At a roundtable meeting of experts, sipuleucel-T data wer...

  13. Comorbidity, Use of Common Medications, and Risk of Early Death in Patients with Localized or Locally Advanced Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Carsten Nieder

    2011-01-01

    Full Text Available In this paper, we analyze predictive factors for early death from comorbidity (defined as death within 3 years from diagnosis and unrelated to prostate cancer in patients with localized or locally advanced prostate cancer. Such information may guide individually tailored treatment or observation strategies, and help to avoid overtreatment. We retrospectively analyzed baseline parameters including information on comorbidity and medication use among 177 patients (median age at diagnosis 70 years. Actuarial survival analyses were performed. During the first 3 years, two patients (1.1% died from progressive prostate cancer after they had developed distant metastases. The risk of dying from other causes (3.4% was numerically higher, although not to a statistically significant degree. Six patients who died from other causes had age-adjusted Charlson comorbidity index (CCI scores ≥5 (CCI is a sum score where each comorbid condition is assigned with a score depending on the risk of dying associated with this condition. The main comorbidity was cardiovascular disease. The two statistically significant predictive factors were medication use and age-adjusted CCI score ≥5 (univariate analysis. However, medication use was not an independent factor as all patients with age-adjusted CCI score ≥5 also used at least one class of medication. Median survival was 30 months in patients with age-adjusted CCI score ≥5. Prediction of non-prostate cancer death may be important to prevent overtreatment in patients who are more threatened by comorbidity. Our data suggest that simple parameters such as use of medications vs. none, or presence of serious cardiac disease vs. none, are not sufficient, and that age-adjusted CCI scores outperform the other factors included in our analysis.

  14. Regional hyperthermia in conjunction with definitive radiotherapy against recurrent or locally advanced prostate cancer T3pNoMo

    Energy Technology Data Exchange (ETDEWEB)

    Tilly, W.; Gellermann, J.; Graf, R.; Felix, R.; Wust, P. [Dept. of Radiation Medicine, Charite Medical School, Berlin (Germany); Hildebrandt, B. [Dept. of Internal Medicine - Hematology and Oncology, Charite Medical School, Berlin (Germany); Weissbach, L. [Dept. of Urology, Urban Hospital, Berlin (Germany); Budach, V. [Dept. of Radiation Oncology, Charite Medical School, Berlin (Germany)

    2005-01-01

    Background and purpose: since long-term results of the standard treatment of locally advanced or recurrent prostatic carcinoma are unsatisfactory, the role for additional regional hyperthermia was evaluated in a phase I/II study. Patients and methods: from 08/1996 to 03/2000, 22 patients were treated by a standard irradiation regimen (68.4 Gy) in combination with regional hyperthermia (weekly, five to six times), and five of 22 patients received short-term (neoadjuvant) hormonal treatment. Of these, 15 patients had primary prostatic carcinoma T3 pNO MO and seven a histologically confirmed local recurrence after radical prostatectomy. Feasibility of hyperthermia, and acute/late toxicity as well as long-term follow-up (prostate-specific antigen [PSA] control, overall survival) were analyzed. Clinical endpoints were correlated with thermal parameters. Results: mean maximum temperatures along the urethra of 41.4 C (41.0 C for the recurrences), and mean T{sub 90} values of 40.7 C could be achieved. Severe acute toxicity of grade 3 occurred at the rectum in three, at the urethra in four, at the intestine in one, and a burn induced by hyperthermia in one of 22 patients. Late toxicity was only observed rectally in one patient (grade 3) and at the urethra in two patients (grade 2). There was no correlation between thermal parameters and any toxicity. The survival curves showed a PSA control for primary prostatic carcinoma > 50% after 6 years, but no long-term PSA control for the recurrences. Overall survival after 6 years was 95% for primary carcinoma, and 60% for the recurrences. There was a clear correlation between higher temperatures or thermal doses with long-term PSA control. Conclusion: regional hyperthermia might be a low-toxicity approach to increase PSA control of common treatment schedules. Further evaluation, in particular employing improved hyperthermia technology, is worthwhile. (orig.)

  15. Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer

    DEFF Research Database (Denmark)

    Idorn, Manja; Køllgaard, Tania; Kongsted, Per

    2014-01-01

    and function of immune suppressive cell subsets in the peripheral blood of 41 patients with prostate cancer (PC) and 36 healthy donors (HD) showed a significant increase in circulating CD14(+) HLA-DR(low/neg) monocytic MDSC (M-MDSC) and Tregs in patients with PC compared to HD. Furthermore, M-MDSC frequencies...... and other cell types may suggest ways to tackle their induction and/or function to improve immunological tumor control....

  16. The HGF/c-MET Axis as a Critical Driver of Resistance to Androgen Suppression in Metastatic Castrate-Resistant Prostate Cancer

    Science.gov (United States)

    2015-10-01

    aspirates from 5 patients. We have obtained 6 blood samples for CTC analyses from 4 patients on abiraterone and 3 blood samples from 2 patients on...bone marrow aspirates has been slower than anticipated. We have addressed this in a number of ways, including pre- screening clinics for eligible...a graphene oxide based microfluidic device (GO Chip) to prostate cancer circulating tumor cell capture and analysis, AACR, 2015. *Patnaik, A

  17. Studying circulating prostate cancer cells by in-vivo flow cytometer

    Science.gov (United States)

    Guo, Jin; Gu, Zhengqin; Chen, Tong; Wang, Cheng; Wei, Xunbin

    2012-03-01

    Prostate cancer is the most common malignancy in American men and the second leading cause of deaths from cancer, after lung cancer. The tumor usually grows slowly and remains confined to the gland for many years. As the cancer advances, however, it can metastasize throughout other areas of the body, such as the bones, lungs, and liver. Surgical resection, hormonal therapy, chemotherapy and radiation therapy are the foundation of current prostate cancer therapies. Treatments for prostate cause both short- and long-term side effects that may be difficult to accept. Molecular mechanisms of prostate cancer metastasis need to be understood better and new therapies must be developed to selectively target to unique characteristics of cancer cell growth and metastasis. We have developed the "in vivo microscopy" to study the mechanisms that govern prostate cancer cell spread through the microenvironment in vivo in real-time confocal near-infrared fluorescence imaging. A recently developed "in vivo flow cytometer" and optical imaging are used to assess prostate cancer cell spreading and the circulation kinetics of prostate cancer cells. We have measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells.

  18. RADICAL PROSTATECTOMY FOR PATIENTS WITH CLINICALLY LOCALIZED AND LOCALLY ADVANCED PROSTATE CANCER: THE REMOTE RESULTS OF TREATEMENT

    Directory of Open Access Journals (Sweden)

    V. N. Grygorenko

    2014-07-01

    Full Text Available The purpose of the work was to improve the treatment results among patients with clinically local and locally advanced prostate cancer while using neo-and/or adjuvant hormone- and radiotherapy.Materials and methods. Radical prostatectomy results estimation was conducted among 170 patients. An average survey period continued 35,99 ± 1,88 (1–102 months. An average age was 61,66 ± 0,45 (40–75 years. Moreover, after operation 125 (73,5 % patients proved to have clinically local forms of prostate cancer (рТ1а,b,c,2aN0М0 – 99, рТ2b,cN0М0 – 26, 25 (14,7 % patients – locally advanced forms (рТ3a,bN0М0 and 19 (11,2 % – generalized forms of prostate cancer (рТ4N0М0, рТ2а,bN1М0,. Metastases in pelvic lymph nodes developed among 10 (5,9 % patients. 43 (25,3 % patients with ІІ–III stages received neoadjuvant hormone therapy treatment due to maximum androgen blockade scheme. An average neoadjuvant hormone therapy duration: 10,14 ± 1,98 (1–60 months. The typical characteristic of modified radical prostatectomy is accurate ejection of urinary bladder neck and proximal area of prostatic urethra part from prostate gland. Already formed urethra-urethral anastomosis is additionally fixed to lateral part of endopelvic fascia.Results. An average 3-year survival made up 95,5 ± 3,5 %, 5-year – 84,1 ± 4,7 %, 7-year – 71,7 ± 6,8 % respectively. 3- and 5-year relapse-free survival comprised 87,05 ± 3,20 %, 79.64 ± 3,03 % 67,11 ± 3,93 % respectively. 5-year survival among patients with localized prostate cancer made up 97,18 ± 3,27 %. 48 (28,2 % patients proved to have biochemical relapse so that they were prescribed adjuvant hormone- and/or radiotherapy treatment. Gleason index ≥ and initial PSA level ≥ 20 ng/ml, and their combination are considered as significant factors that foresee Т > Т2 category and biochemical relapse. For рN+ category initial PSA ≥ 20 ng/ml level is principle. Frequency of disease relapse

  19. RADICAL PROSTATECTOMY FOR PATIENTS WITH CLINICALLY LOCALIZED AND LOCALLY ADVANCED PROSTATE CANCER: THE REMOTE RESULTS OF TREATEMENT

    Directory of Open Access Journals (Sweden)

    V. N. Grygorenko

    2013-01-01

    Full Text Available The purpose of the work was to improve the treatment results among patients with clinically local and locally advanced prostate cancer while using neo-and/or adjuvant hormone- and radiotherapy.Materials and methods. Radical prostatectomy results estimation was conducted among 170 patients. An average survey period continued 35,99 ± 1,88 (1–102 months. An average age was 61,66 ± 0,45 (40–75 years. Moreover, after operation 125 (73,5 % patients proved to have clinically local forms of prostate cancer (рТ1а,b,c,2aN0М0 – 99, рТ2b,cN0М0 – 26, 25 (14,7 % patients – locally advanced forms (рТ3a,bN0М0 and 19 (11,2 % – generalized forms of prostate cancer (рТ4N0М0, рТ2а,bN1М0,. Metastases in pelvic lymph nodes developed among 10 (5,9 % patients. 43 (25,3 % patients with ІІ–III stages received neoadjuvant hormone therapy treatment due to maximum androgen blockade scheme. An average neoadjuvant hormone therapy duration: 10,14 ± 1,98 (1–60 months. The typical characteristic of modified radical prostatectomy is accurate ejection of urinary bladder neck and proximal area of prostatic urethra part from prostate gland. Already formed urethra-urethral anastomosis is additionally fixed to lateral part of endopelvic fascia.Results. An average 3-year survival made up 95,5 ± 3,5 %, 5-year – 84,1 ± 4,7 %, 7-year – 71,7 ± 6,8 % respectively. 3- and 5-year relapse-free survival comprised 87,05 ± 3,20 %, 79.64 ± 3,03 % 67,11 ± 3,93 % respectively. 5-year survival among patients with localized prostate cancer made up 97,18 ± 3,27 %. 48 (28,2 % patients proved to have biochemical relapse so that they were prescribed adjuvant hormone- and/or radiotherapy treatment. Gleason index ≥ and initial PSA level ≥ 20 ng/ml, and their combination are considered as significant factors that foresee Т > Т2 category and biochemical relapse. For рN+ category initial PSA ≥ 20 ng/ml level is principle. Frequency of disease relapse

  20. Leuprorelin Acetate in Prostate Cancer: a European Update

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    Persad R

    2002-01-01

    Full Text Available This review provides an update on leuprorelin acetate, the world's most widely prescribed depot luteinising hormone-releasing hormone analogue. Leuprorelin acetate has been in clinical use in the palliative treatment of prostate cancer for more than 20 years, but advances continue to be made in terms of convenience and flexibility of administration, and in the incorporation of leuprorelin acetate into novel treatment regimens. The drug is administered in the form of a depot injection containing leuprorelin acetate microspheres, and is at least as effective in suppressing testosterone secretion as orchiectomy. In patients with prostate cancer, serum testosterone levels are reduced to castrate levels (= 50 ng/dl within 2-3 weeks of the first one-month depot injection of 3.75 mg or three-month depot injection of 11.25 mg. Both the one-month and three-month formulations are effective in delaying tumour progression and alleviating symptoms of locally advanced and metastatic prostate cancer. Tolerability is generally good, with side-effects reflecting effective testosterone suppression. Recent studies have investigated the place of leuprorelin acetate as part of continuous or intermittent maximal androgen blockade (MAB and in neoadjuvant therapy (ie, to reduce the size of the prostate and downsize the tumour before radiotherapy. Additional formulations and presentations are in development, including a six-month injection, with the aim of adding to the clinical flexibility and patient acceptability of this important palliative treatment for prostate cancer.

  1. Efficacy and Safety of Combined Androgen Deprivation Therapy (ADT and Docetaxel Compared with ADT Alone for Metastatic Hormone-Naive Prostate Cancer: A Systematic Review and Meta-Analysis.

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    Tobias Engel Ayer Botrel

    Full Text Available Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in older men in the United States (USA and Western Europe. Androgen-deprivation therapy alone (ADT remains the first line of treatment in most cases, for metastatic disease. We performed a systematic review and meta-analysis of all randomized controlled trials (RCT that compared the efficacy and adverse events profile of a chemohormonal therapy (ADT ± docetaxel for metastatic hormone-naive prostate cancer (mHNPC.Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoint was overall survival. Data extracted from the studies were combined by using the hazard ratio (HR or risk ratio (RR with their corresponding 95% confidence intervals (95% CI.The final analysis included 3 trials comprising 2,264 patients (mHNPC. Patients who received the chemohormonal therapy had a longer clinical progression-free survival interval (HR = 0.64; 95% CI: 0.55 to 0.75; p<0.00001, and no heterogeneity (Chi2 = 0.64; df = 1 [p = 0.42]; I2 = 0%. The biochemical progression-free survival (bPFS also was higher in patients treated with ADT plus docetaxel (HR = 0.63; 95% CI: 0.57 to 0.69; p<0.00001, also with no heterogeneity noted (Chi2 = 0.48; df = 2 [p = 0.79]; I2 = 0%. Finally, the combination of ADT with docetaxel showed a superior overall survival (OS compared with ADT alone (HR = 0.73; 95% CI: 0.64 to 0.84; p<0.0001, with moderate heterogeneity (Chi2 = 3.84; df = 2 [p = 0.15]; I2 = 48%. A random-effects model analysis was performed, and the results remained favorable to the use of ADT plus docetaxel (HR = 0.73; 95% CI: 0.60 to 0.89; p = 0.002. In the final combined analysis of the high-volume disease patients, the use of the combination therapy also favored an increased overall survival (HR = 0.67; 95% CI: 0.54 to 0.83; p = 0.0003. Regarding adverse events and severe toxicity (grade ≥3, the group receiving the combined therapy

  2. Looking beyond Androgen Receptor Signaling in the Treatment of Advanced Prostate Cancer

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    Benjamin Sunkel

    2014-01-01

    Full Text Available This review will provide a description of recent efforts in our laboratory contributing to a general goal of identifying critical determinants of prostate cancer growth in both androgen-dependent and -independent contexts. Important outcomes to date have indicated that the sustained activation of AR transcriptional activity in castration-resistant prostate cancer (CRPC cells results in a gene expression profile separate from the androgen-responsive profile of androgen-dependent prostate cancer (ADPC cells. Contributing to this reprogramming is enhanced FoxA1 recruitment of AR to G2/M phase target gene loci and the enhanced chromatin looping of CRPC-specific gene regulatory elements facilitated by PI3K/Akt-phosphorylated MED1. We have also observed a role for FoxA1 beyond AR signaling in driving G1/S phase cell cycle progression that relies on interactions with novel collaborators MYBL2 and CREB1. Finally, we describe an in-depth mechanism of GATA2-mediated androgen-responsive gene expression in both ADPC and CRPC cells. Altogether these efforts provide evidence to support the development of novel prostate cancer therapeutics that address downstream targets of AR activity as well as AR-independent drivers of disease-relevant transcription programs.

  3. Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—Preliminary Results of the Response Evaluation Using F-18-Fluoride PET/CT

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    Kalevi Kairemo

    2015-10-01

    Full Text Available The purpose of this study was to evaluate the outcome after Radium-223-dichloride (223RaCl2 treatment of patients with skeletal metastases of castration resistant prostate cancer using whole-body 18F-Fluoride PET/CT. Sodium 18F-fluoride [18F]-NaF PET/CT was performed prior the treatment of 223RaCl2, after the first cycle and after the sixth cycle. The skeletal metastases were analyzed quantitatively using modified PET response evaluation PERCIST criteria. The patients were also analyzed for S-PSA. All ten patients responded in [18F]-NaF scans after 6 cycles, but interim analysis after the 1st cycle did not give additional information about the outcome. The S-PSA decrease correlated with [18F]-NaF response, only 1 patient demonstrated progressive disease, i.e., >25% increase in S-PSA values during 223RaCl2. Our results (although preliminary suggest that 18F-Fluoride PET/CT is useful in the follow-up of castration resistant prostate cancer with skeletal metastases.

  4. A software tool for advanced MRgFUS prostate therapy planning and follow up

    Science.gov (United States)

    van Straaten, Dörte; Hoogenboom, Martijn; van Amerongen, Martinus J.; Weiler, Florian; Issawi, Jumana Al; Günther, Matthias; Fütterer, Jurgen; Jenne, Jürgen W.

    2017-03-01

    US guided HIFU/FUS ablation for the therapy of prostate cancer is a clinical established method, while MR guided HIFU/FUS applications for prostate recently started clinical evaluation. Even if MRI examination is an excellent diagnostic tool for prostate cancer, it is a time consuming procedure and not practicable within an MRgFUS therapy session. The aim of our ongoing work is to develop software to support therapy planning and post-therapy follow-up for MRgFUS on localized prostate cancer, based on multi-parametric MR protocols. The clinical workflow of diagnosis, therapy and follow-up of MR guided FUS on prostate cancer was deeply analyzed. Based on this, the image processing workflow was designed and all necessary components, e.g. GUI, viewer, registration tools etc. were defined and implemented. The software bases on MeVisLab with several implemented C++ modules for the image processing tasks. The developed software, called LTC (Local Therapy Control) will register and visualize automatically all images (T1w, T2w, DWI etc.) and ADC or perfusion maps gained from the diagnostic MRI session. This maximum of diagnostic information helps to segment all necessary ROIs, e.g. the tumor, for therapy planning. Final therapy planning will be performed based on these segmentation data in the following MRgFUS therapy session. In addition, the developed software should help to evaluate the therapy success, by synchronization and display of pre-therapeutic, therapy and follow-up image data including the therapy plan and thermal dose information. In this ongoing project, the first stand-alone prototype was completed and will be clinically evaluated.

  5. Prostate Cancer and Sexual Function

    OpenAIRE

    Hyun, Jae Saog

    2012-01-01

    Prostate cancer is now ranked fifth in incidence among cancers in Korean adult males. This is attributable to the more Westernized dietary style which increases the morbidity of prostate cancer and the development of cancer diagnostic technologies, such as prostate-specific antigen and advanced medical systems, increasing the rate of prostate cancer diagnosis. Prostate cancer effects include not only erectile dysfunction caused by the disease itself, but also by psychiatric disorders caused b...

  6. Vegetable and fruit intake after diagnosis and risk of prostate cancer progression.

    Science.gov (United States)

    Richman, Erin L; Carroll, Peter R; Chan, June M

    2012-07-01

    Cruciferous vegetables, tomato sauce and legumes have been associated with reduced risk of incident advanced prostate cancer. In vitro and animal studies suggest these foods may inhibit progression of prostate cancer, but there are limited data in men. Therefore, we prospectively examined whether intake of total vegetables, and specifically cruciferous vegetables, tomato sauce and legumes, after diagnosis reduce risk of prostate cancer progression among 1,560 men diagnosed with non-metastatic prostate cancer and participating in the Cancer of the Prostate Strategic Urologic Research Endeavor, a United States prostate cancer registry. As a secondary analysis, we also examined other vegetable subgroups, total fruit and subgroups of fruits. The participants were diagnosed primarily at community-based clinics and followed from 2004 to 2009. We assessed vegetable and fruit intake via a semi-quantitative food frequency questionnaire, and ascertained prostate cancer outcomes via urologist report and medical records. We observed 134 events of progression (53 biochemical recurrences, 71 secondary treatments likely due to recurrence, 6 bone metastases and 4 prostate cancer deaths) during 3,171 person-years. Men in the fourth quartile of post-diagnostic cruciferous vegetable intake had a statistically significant 59% decreased risk of prostate cancer progression compared to men in the lowest quartile (hazard ratio (HR): 0.41; 95% confidence interval (CI): 0.22, 0.76; p-trend: 0.003). No other vegetable or fruit group was statistically significantly associated with risk of prostate cancer progression. In conclusion, cruciferous vegetable intake after diagnosis may reduce risk of prostate cancer progression.

  7. The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells

    Energy Technology Data Exchange (ETDEWEB)

    Gough, Mallory, E-mail: m.gough1@lancaster.ac.uk; Blanthorn-Hazell, Sophee, E-mail: s.blanthorn-hazell@lancaster.ac.uk; Delury, Craig, E-mail: c.delury@lancaster.ac.uk; Parkin, Edward, E-mail: e.parkin@lancaster.ac.uk

    2014-10-31

    Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enable cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.

  8. Exosomes from bulk and stem cells from human prostate cancer have a differential microRNA content that contributes cooperatively over local and pre-metastatic niche.

    Science.gov (United States)

    Sánchez, Catherine A; Andahur, Eliana I; Valenzuela, Rodrigo; Castellón, Enrique A; Fullá, Juan A; Ramos, Christian G; Triviño, Juan C

    2016-01-26

    The different prostate cancer (PCa) cell populations (bulk and cancer stem cells, CSCs) release exosomes that contain miRNAs that could modify the local or premetastatic niche. The analysis of the differential expression of miRNAs in exosomes allows evaluating the differential biological effect of both populations on the niche, and the identification of potential biomarkers and therapeutic targets. Five PCa primary cell cultures were established to originate bulk and CSCs cultures. From them, exosomes were purified by precipitation for miRNAs extraction to perform a comparative profile of miRNAs by next generation sequencing in an Illumina platform. 1839 miRNAs were identified in the exosomes. Of these 990 were known miRNAs, from which only 19 were significantly differentially expressed: 6 were overexpressed in CSCs and 13 in bulk cells exosomes. miR-100-5p and miR-21-5p were the most abundant miRNAs. Bioinformatics analysis indicated that differentially expressed miRNAs are highly related with PCa carcinogenesis, fibroblast proliferation, differentiation and migration, and angiogenesis. Besides, miRNAs from bulk cells affects osteoblast differentiation. Later, their effect was evaluated in normal prostate fibroblasts (WPMY-1) where transfection with miR-100-5p, miR-21-5p and miR-139-5p increased the expression of metalloproteinases (MMPs) -2, -9 and -13 and RANKL and fibroblast migration. The higher effect was achieved with miR21 transfection. As conclusion, miRNAs have a differential pattern between PCa bulk and CSCs exosomes that act collaboratively in PCa progression and metastasis. The most abundant miRNAs in PCa exosomes are interesting potential biomarkers and therapeutic targets.

  9. Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma

    DEFF Research Database (Denmark)

    Judson, Ian; Verweij, Jaap; Gelderblom, Hans;

    2014-01-01

    routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with doxorubicin alone. METHODS: We did this phase 3 randomised controlled trial (EORTC 62012) at 38 hospitals in ten countries...

  10. Predictive effect of androgen receptor splice variant 7 expression on time to castration resistance in patients with metastatic prostate cancer%前列腺癌组织中雄激素受体剪接变异体7表达对转移性前列腺癌患者激素敏感时间的预测作用

    Institute of Scientific and Technical Information of China (English)

    瞿元元; 叶定伟; 戴波; 孔蕴毅; 蔡旭; 常坤; 孙自捷; 张海梁; 朱耀

    2014-01-01

    receptor splice variant 7 (AR-V7) expression on time to castration resistance in patients with metastatic prostate cancer.Methods The data of 113 cases of advanced metastatic prostate cancer diagnosed by prostate biopsy in our institute from Jan.2002 to Jun.2010 were collected retrospectively.The median age at diagnosis was 70 years,ranged from 43 to 84 years.The median tPSA was 120.0 μg/L,ranged from 3.0 to 6 006.2 μg/L.There were 5 patients in M1a(4.4%),94 patients in M1b(83.2%) and 14 patients in M1c(12.4%).All patients received hormonal therapy.1mmunohistochemical staining and AR-V7 specific antibody were used to detect the expression of AR-V7 in prostate cancer tissues.Cox regression models were used to analyze the predictive role of patient characteristics including patient's age at diagnosis,tPSA level at diagnosis,Gleason score,clinical stage,PSA nadir during hormonal therapy,the time to PSA nadir and PSA half-life.The effect of AR-V7 expression on time to castration resistance was analyzed using Kaplan-Meier curves,and the differences were assessed using the log-rank test.Results The PSA nadir ranged from 0.0 to 143.0 μg/L and the median value was 0.7 μg/L.The time to PSA nadir ranged from 0.9 to 71.0 months and the median value was 8.1 months.The median PSA half life was 1.0 month,which ranged from 0.1 to 41.0 months.Followed up for a median time of 27 months,100 patients progressed to castration-resistant prostate cancer (CRPC) and the median time to castration resistance was 24 months.The expression of AR-V7 was positive in 23 out of 113 patients.Multivariate analysis showed that the expression of AR-V7 in prostate cancer (P=0.004,HR =2.223) and PSA nadir during hormonal therapy (P =0.035,HR =1.011) were independent predictive factors of time to castration resistance.The median time to castration resistance for patients with and without AR-V7 expression were (16.04±3.4) months and (30.04-6.0) months,respectively (P=0.001).Conclusions The expression

  11. TRPV6 alleles do not influence prostate cancer progression

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    Flockerzi Veit

    2009-10-01

    Full Text Available Abstract Background The transient receptor potential, subfamily V, member 6 (TRPV6 is a Ca2+ selective cation channel. Several studies have shown that TRPV6 transcripts are expressed in locally advanced prostatic adenocarcinoma, metastatic and androgen-insensitive prostatic lesions but are undetectable in healthy prostate tissue and benign prostatic hyperplasia. Two allelic variants of the human trpv6 gene have been identified which are transcribed into two independent mRNAs, TRPV6a and TRPV6b. We now asked, whether the trpv6a allele is correlated with the onset of prostate cancer, with the Gleason score and the tumour stage. Methods Genomic DNA of prostate cancer patients and control individuals was isolated from resections of prostatic adenocarcinomas and salivary fluid respectively. Genotyping of SNPs of the TRPV6 gene was performed by restriction length polymorphism or by sequencing analysis. RNA used for RT-PCR was isolated from prostate tissue. Data sets were analyzed by Chi-Square test. Results We first characterized in detail the five polymorphisms present in the protein coding exons of the trpv6 gene and show that these polymorphisms are coupled and are underlying the TRPV6a and the TRPV6b variants. Next we analysed the frequencies of the two TRPV6 alleles using genomic DNA from saliva samples of 169 healthy individuals. The homozygous TRPV6b genotype predominated with 86%, whereas no homozygous TRPV6a carriers could be identified. The International HapMap Project identified a similar frequency for an Utah based population whereas in an African population the a-genotype prevailed. The incidence of prostate cancer is several times higher in African populations than in non-African and we then investigated the TRPV6a/b frequencies in 141 samples of prostatic adenocarcinoma. The TRPV6b allele was found in 87% of the samples without correlation with Gleason score and tumour stage. Conclusion Our results show that the frequencies of trpv6

  12. Preferred treatment frequency in patients receiving androgen deprivation therapy for advanced prostate cancer

    DEFF Research Database (Denmark)

    Fode, Mikkel; Nielsen, Torben K; Al-Hamadani, Muhammad;

    2014-01-01

    for analysis. A total of 38.1% of participants preferred frequent treatment ("Every month", "Every third month"), 32.4% preferred infrequent treatment ("Every sixth month", "Every twelfth month") and 29.6% stated that length of the treatment intervals made no difference (p = 0.37). Patients with disease......OBJECTIVE: The aim of this study was to assess patient preference regarding the length of treatment intervals of androgen deprivation therapy (ADT) with gonadotropin-releasing hormone agonists for prostate cancer. MATERIAL AND METHODS: The study was conducted as a questionnaire-based, cross...... satisfaction and side-effects. Overall, 238 men receiving ADT for prostate cancer were presented with the questionnaire between September 2011 and May 2012. Descriptive statistics, the chi-squared test and multiple regression were used for analyses. RESULTS: In total, 176 questionnaires (74%) were available...

  13. Development of Personalized Cancer Therapy for Men with Advanced Prostate Cancer

    Science.gov (United States)

    2015-10-01

    prostate cancer in urine ; Validate the ERG rearrangement FISH assay on tissues and determine the prevalence of ERG rearrangements in isolated...Logothetis, Araujo, Troncoso, and Chinnaiyan) to determine whether the patients’ responses to therapy were predicted by our responder ID profile hypothesis...BGJ398; Novartis Pharmaceuticals), is the lead compound being tested as anticancer therapy by Novartis. In addition, in an agreement with Janssen

  14. Phellinus linteus extract sensitizes advanced prostate cancer cells to apoptosis in athymic nude mice.

    Science.gov (United States)

    Tsuji, Takanori; Du, Wei; Nishioka, Takashi; Chen, Lihua; Yamamoto, Daisuke; Chen, Chang Yan

    2010-03-31

    Phellinus linteus (PL) mushroom possesses anti-tumor property. We previously reported that the treatment with PL caused cultured human prostate cancer cells to undergo apoptosis. To further studying the mechanisms of PL-mediated apoptosis, we performed xenograft assay, together with in vitro assays, to evaluate the effect of PL on the genesis and progression of the tumors formed from the inoculation of prostate cancer PC3 or DU145 cells. After the inoculation, nude mice were injected with PL every two days for 12 days. Although PL treatment did not prevent the formation of the inoculated tumors, the growth rate of the tumors after PL treatment was dramatically attenuated. We then tested the effect of PL on the tumors 12 days after the inoculation. After inoculated tumors reached a certain size, PL was administrated to the mice by subcutaneous injection. The histochemistry or immunochemistry analysis showed that apoptosis occurred with the activation of caspase 3 in the tumors formed by inoculating prostate cancer DU145 or PC3 cells. The data was in a good agreement with that from cultured cells. Thus, our in vivo study suggests that PL not only is able to attenuate tumor growth, but also to cause tumor regression by inducing apoptosis.

  15. Phellinus linteus extract sensitizes advanced prostate cancer cells to apoptosis in athymic nude mice.

    Directory of Open Access Journals (Sweden)

    Takanori Tsuji

    Full Text Available Phellinus linteus (PL mushroom possesses anti-tumor property. We previously reported that the treatment with PL caused cultured human prostate cancer cells to undergo apoptosis. To further studying the mechanisms of PL-mediated apoptosis, we performed xenograft assay, together with in vitro assays, to evaluate the effect of PL on the genesis and progression of the tumors formed from the inoculation of prostate cancer PC3 or DU145 cells. After the inoculation, nude mice were injected with PL every two days for 12 days. Although PL treatment did not prevent the formation of the inoculated tumors, the growth rate of the tumors after PL treatment was dramatically attenuated. We then tested the effect of PL on the tumors 12 days after the inoculation. After inoculated tumors reached a certain size, PL was administrated to the mice by subcutaneous injection. The histochemistry or immunochemistry analysis showed that apoptosis occurred with the activation of caspase 3 in the tumors formed by inoculating prostate cancer DU145 or PC3 cells. The data was in a good agreement with that from cultured cells. Thus, our in vivo study suggests that PL not only is able to attenuate tumor growth, but also to cause tumor regression by inducing apoptosis.

  16. New Prostate Cancer Treatment Target

    Science.gov (United States)

    Researchers have identified a potential alternative approach to blocking a key molecular driver of an advanced form of prostate cancer, called androgen-independent or castration-resistant prostate cancer.

  17. Promoter-Based Theranostics for Prostate Cancer

    Science.gov (United States)

    2015-10-01

    1). In order to test this in vivo, we have developed a mouse model of human metastatic prostate cancer that develops tumors within liver, kidney ...mouse model of human prostate Cancer. (a) Bioluminescent images of mice with metastatic model. (b) Liver metastasis. (c) Kidney metastasis. (d...targeting clear cell renal cell carcinoma using carbonic anhydrase IX as a target. Title: Shape control and transport properties of DNA-templated

  18. Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

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    Sergio Szyldergemajn

    2009-09-01

    Full Text Available The objective of this exploratory, open-label, single-arm, phase II clinical trial was to evaluate plitidepsin (5 mg/m2 administered as a 3-hour continuous intravenous infusion every two weeks to patients with locally advanced/metastatic transitional cell carcinoma of the urothelium who relapsed/progressed after first-line chemotherapy. Treatment cycles were repeated for up to 12 cycles or until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. The primary efficacy endpoint was objective response rate according to RECIST. Secondary endpoints were the rate of SD lasting ≥6 months and time-to-event variables. Toxicity was assessed using NCI-CTC v. 3.0. Twenty-one patients received 57 treatment cycles. No objective tumor responses occurred. SD lasting <6 months was observed in two of 18 evaluable patients. With a median follow-up of 4.6 months, the median PFR and the median OS were 1.4 months and 2.3 months, respectively. The most common AEs were mild to moderate nausea, fatigue, myalgia and anorexia. Anemia, lymphopenia, and increases in transaminases, alkaline phosphatase and creatinine were the most frequent laboratory abnormalities. No severe neutropenia occurred. Treatment was feasible and generally well tolerated in this patient population; however the lack of antitumor activity precludes further studies of plitidepsin in this setting.

  19. Gemcitabine Plus Docetaxel Versus Docetaxel in Patients With Predominantly Human Epidermal Growth Factor Receptor 2-Negative Locally Advanced or Metastatic Breast Cancer: A Randomized, Phase III Study by the Danish Breast Cancer Cooperative Group

    DEFF Research Database (Denmark)

    Nielsen, Dorte L; Bjerre, Karsten D; Jakobsen, Erik H;

    2011-01-01

    PURPOSE The objective of this phase III study was to compare the efficacy of gemcitabine plus docetaxel (GD) versus docetaxel in patients with advanced breast cancer. PATIENTS AND METHODS Predominantly human epidermal growth factor receptor 2 (HER2) -negative patients were randomly assigned to ge...... GD compared with docetaxel demonstrated increased TTP in metastatic breast cancer. However, RR and OS were similar. Thus, the addition of gemcitabine failed to demonstrate any clinically meaningful benefit when combined with docetaxel....

  20. First- and second-line treatment of advanced metastatic non-small-cell lung cancer: a global view

    Directory of Open Access Journals (Sweden)

    Thatcher Nicholas

    2008-09-01

    Full Text Available Abstract Treatment of non-small-cell lung cancer is dependent on disease stage. For patients with metastasis or locally advanced disease, the importance of finding therapeutic schemes that may benefit this population is important. This review discusses therapeutic options for first- and second-line treatment in patients with advanced non-small-cell lung cancer. According to current data, the combination of two cytotoxic agents is the optimum first-line treatment for patients with non-small-cell lung cancer and performance status of 0–1. Addition of bevacizumab has shown to provide an even longer survival and to increase response rate. Within the first-line setting, erlotinib appears to be effective in the treatment of elderly patients who would not derive a benefit from standard chemotherapy or those refusing standard chemotherapy. The administration of erlotinib as first-line maintenance therapy is being assessed. There are currently three drugs approved for second-line treatment of patients with advanced non-small-cell lung cancer after failure of first-line chemotherapy. These drugs have proven to be effective in phase III trials. In the phase III trial BR.21 study, the response rate was 8.9% in the erlonitib group, and less than 1% in placebo; median response duration was 7.9 months and 3.7 months, respectively; and the median survival was 6.7 months and 4.7 with erlotinib and placebo, respectively. One-year survival was 31% and 21% with erlotinib and placebo, respectively. In addition, the BR.21 trial revealed that significantly greater improvements in overall quality of life and in both physical and emotional functioning were observed in the erlotinib arm as compared with the placebo arm. Erlotinib is not significantly associated with hematologic adverse effects. Erlotinib is administered orally, and does not require concomitant administration of other drugs, thus causing patients less inconvenience. Analysis of data from different

  1. The E1 copper binding domain of full-length amyloid precursor protein mitigates copper-induced growth inhibition in brain metastatic prostate cancer DU145 cells.

    Science.gov (United States)

    Gough, Mallory; Blanthorn-Hazell, Sophee; Delury, Craig; Parkin, Edward

    2014-10-31

    Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enable cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.

  2. The Effect of Prior Androgen Synthesis Inhibition on Outcomes of Subsequent Therapy with Docetaxel in Patients with Metastatic Castrate Resistant Prostate Cancer: Results from a Retrospective Analysis of a Randomized Phase 3 Clinical Trial (CALGB 90401) (Alliance)

    Science.gov (United States)

    Aggarwal, Rahul; Halabi, Susan; Kelly, William Kevin; George, Daniel; Mahoney, John F.; Millard, Frederick; Stadler, Walter M.; Morris, Michael J.; Kantoff, Philip; Monk, J. Paul; Carducci, Michael; Small, Eric J.

    2013-01-01

    Background Preliminary data suggests a potential decreased benefit of docetaxel in metastatic castration-resistant prostate cancer (mCRPC) patients previously treated with abiraterone acetate, a novel androgen synthesis inhibitor (ASI). CALGB 90401 (Alliance), a phase 3 trial of mCRPC patients treated with docetaxel-based chemotherapy, offered the opportunity to evaluate effect of prior ketoconazole, an earlier generation ASI, on clinical outcomes following docetaxel. Methods CALGB 90401 randomized 1050 men with chemotherapy-naïve, mCRPC to treatment with docetaxel and prednisone with either bevacizumab or placebo. 1005 men (96%) had data available regarding prior ketoconazole therapy. The effect of prior ketoconazole on overall survival (OS), progression-free survival (PFS), PSA decline, and objective response rate (ORR) observed was assessed using proportional hazards and Poisson regression method adjusted for validated prognostic factors and treatment arm. Results Baseline characteristics between patients with (N=277) and without (N=728) prior ketoconazole therapy were similar. There were no statistically significant differences between patients with and without prior ketoconazole therapy with respect to OS (median OS 21.1 vs. 22.3 months, stratified log-rank p-value=0.635); PFS (median PFS 8.1 vs. 8.6 months, stratified log-rank p-value=0.342); ≥50% PSA decline (61% vs. 66%, relative risk=1.09, adjusted p-value=0.129); or ORR (39% vs. 43%, relative risk=1.11, adjusted p-value=0.366). Conclusions As measured by OS, PFS, PSA and ORR, there is no evidence that prior treatment with ketoconazole impacts clinical outcomes in mCRPC patients treated with subsequent docetaxel-based therapy. Prospective studies are needed to assess for potential cross-resistance with novel ASIs and to define the optimal sequence of therapy in mCRPC. PMID:23913744

  3. Statin derivatives as therapeutic agents for castration-resistant prostate cancer.

    Science.gov (United States)

    Ingersoll, Matthew A; Miller, Dannah R; Martinez, October; Wakefield, C Brent; Hsieh, Kuan-Chan; Simha, M Vijaya; Kao, Chai-Lin; Chen, Hui-Ting; Batra, Surinder K; Lin, Ming-Fong

    2016-12-01

    Despite recent advances in modern medicine, castration-resistant prostate cancer remains an incurable disease. Subpopulations of prostate cancer cells develop castration-resistance by obtaining the complete steroidogenic ability to synthesize androgens from cholesterol. Statin derivatives, such as simvastatin, inhibit cholesterol biosynthesis and may reduce prostate cancer incidence as well as progression to advanced, metastatic phenotype. In this study, we demonstrate novel simvastatin-related molecules SVA, AM1, and AM2 suppress the tumorigenicity of prostate cancer cell lines including androgen receptor-positive LNCaP C-81 and VCaP as well as androgen receptor-negative PC-3 and DU145. This is achieved through inhibition of cell proliferation, colony formation, and migration as well as induction of S-phase cell-cycle arrest and apoptosis. While the compounds effectively block androgen receptor signaling, their mechanism of inhibition also includes suppression of the AKT pathway, in part, through disruption of the plasma membrane. SVA also possess an added effect on cell growth inhibition when combined with docetaxel. In summary, of the compounds studied, SVA is the most potent inhibitor of prostate cancer cell tumorigenicity, demonstrating its potential as a promising therapeutic agent for castration-resistant prostate cancer.

  4. Organoid culture systems for prostate epithelial and cancer tissue

    NARCIS (Netherlands)

    Drost, Jarno; Karthaus, Wouter R; Gao, Dong; Driehuis, Else; Sawyers, Charles L; Chen, Yu; Clevers, Hans

    2016-01-01

    This protocol describes a strategy for the generation of 3D prostate organoid cultures from healthy mouse and human prostate cells (either bulk or FACS-sorted single luminal and basal cells), metastatic prostate cancer lesions and circulating tumor cells. Organoids derived from healthy material cont

  5. Collision tumor of kidney: A case of renal cell carcinoma with metastases of prostatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Monika Vyas

    2013-01-01

    Full Text Available Simultaneous occurrence of prostatic adenocarcinoma and renal cell carcinoma is well documented in the literature. However, metastatic prostatic adenocarcinoma in a kidney harboring a renal cell carcinoma (RCC is quite rare. Although renal cell carcinoma is the most common tumor that can harbor metastasis, metastatic prostatic adenocarcinoma in a kidney harboring a RCC is quite rare. There are four cases in the literature showing metastasis of prostatic adenocarcinoma to RCC. However, as per our knowledge, this is the first case of a collision between RCC and metastatic prostatic adenocarcinoma.

  6. QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    Science.gov (United States)

    2016-10-26

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  7. Prostate Problems

    Science.gov (United States)

    ... know the exact cause of your prostate problem. Prostatitis The cause of prostatitis depends on whether you ... prostate problem in men older than age 50. Prostatitis If you have a UTI, you may be ...

  8. First Line Androgen Deprivation Therapy Duration Is Associated with the Efficacy of Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer after Docetaxel

    Science.gov (United States)

    Li, Jian-Ri; Wang, Shian-Shiang; Yang, Cheng-Kuang; Chen, Chuan-Su; Ho, Hao-Chung; Chiu, Kun-Yuan; Hung, Chi-Feng; Cheng, Chen-Li; Yang, Chi-Rei; Chen, Cheng-Che; Wang, Shu-Chi; Lin, Chia-Yen; Ou, Yen-Chuan

    2017-01-01

    Introduction: We performed a chart review study in our castration-resistant prostate cancer (CRPC) patients who received Abiraterone acetate (AA) treatment after docetaxel and identified clinical markers which can predict treatment outcome. Materials and Methods: From 2012 to 2016, 64 patients who received docetaxel after CRPC followed by AA treatment were included. Clinical parameters were recorded and analysis was performed to identify associations between pre-treatment variables and treatment outcome. Results: Thirty three patients (51.6%) achieved a decrease in PSA of 50%. The median PSA progression-free survival and overall survival in the total cohort of 64 patients were 6.6 and 24 months, respectively. Adverse events (AEs) in all grades developed in 35.9% (23/64) patients and mostly were grade 1 or 2. The most common AEs were gastric upset, hypokalemia and elevated liver function tests. Of the eight variables analyzed, first line androgen deprivation therapy (ADT) duration showed positive association to progression free survival (HR 0.98, 95% CI [0.96–0.99], p = 0.012) and overall survival (HR 0.97, 95% CI [0.94–0.99], p = 0.019). Pre-AA PSA and PSA progression ratio showed negative association only to progression free survival (HR 1.0, 95% CI [1.000–1.002], p = 0.025, HR 1.01, 95% CI [1.00–1.01], p < 0.001, respectively). Conclusion: First line ADT duration was positively associated with AA treatment efficacy in progression free survival and overall survival. It can be used as a pre-treatment predictor. PMID:28243202

  9. Immunoendocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin of locally advanced or metastatic endocrine tumors.

    Science.gov (United States)

    Lissoni, P; Barni, S; Tancini, G; Mainini, E; Piglia, F; Maestroni, G J; Lewinski, A

    1995-01-01

    Recent evidence has shown that endocrine tumors are under an endocrine and an immune regulation, and that biotherapies with interferon or the long-acting somatostatin analog octreotide may be effective in the control of tumor growth and clinical symptomatology. Within the biotherapies of tumors, interleukin-2(IL-2) has appeared to play an essential role in the antitumor immune response. Despite its important antitumor role, very few studies have been carried out to investigate the possible use of IL-2 in the treatment of advanced endocrine tumors. Its potential toxicity would represent the main limiting factor for the clinical experiments with IL-2. Our previous studies have shown that the pineal hormone melatonin (MLT) may amplify the antitumor activity of IL-2, either through immunomodulating mechanisms or through a direct cytostatic activity by inhibiting tumor growth factor production. On this basis, we have performed a phase II pilot study with low-dose IL-2 plus MLT in 14 patients with untreatable endocrine tumors because of disseminated disease, lack of response to previous standard biotherapies or chemotherapies, or tumors for whom no effective therapy is available. Thyroid cancers, carcinoid and endodrine pancreatic tumors were the most frequent neoplasms. IL-2 was given at 3 million IU/day s.c. at 8 p.m. for 6 days/week for 4 weeks, corresponding to one cycle. MLT was given orally at 40 mg/day at 8 p.m. every day. In nonprogressed patients, a second cycle was given after a 21-day rest period. Patients were considered as evaluable when they received at least one complete cycle, and 12 patients were fully evaluable. According to WHO criteria, a partial response was achieved in 3/12 (25%) patients (carcinoid tumor: 1; neuroendocrine lung tumor: 1; pancreatic islet cell tumor: 1). Another patient with gastrinoma had a more than 50% reduction of tumor markers. Toxicity was low in all patients. This preliminary study suggests that low-dose IL-2 immunotherapy in

  10. Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

    Science.gov (United States)

    Inal, A; Kos, F T; Algin, E; Yildiz, R; Dikiltas, M; Unek, I T; Colak, D; Elkiran, E T; Helvaci, K; Geredeli, C; Dane, F; Balakan, O; Kaplan, M A; Durnali, A G; Harputoglu, H; Goksel, G; Ozdemir, N; Buyukberber, S; Gumus, M; Kucukoner, M; Ozkan, M; Uncu, D; Benekli, M; Isikdogan, A

    2012-01-01

    The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

  11. Clinical outcome of advanced and metastatic renal cell carcinoma treated with targeted therapy: is there a difference between young and old patients?

    Directory of Open Access Journals (Sweden)

    Zhang G

    2014-11-01

    Full Text Available Guiming Zhang,1,2,* Yao Zhu,1,2,* Dahai Dong,3 Weijie Gu,1,2 Hailiang Zhang,1,2 Lijiang Sun,3 Dingwei Ye1,2 1Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China; 3Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, People's Republic of China *These authors contributed equally to this work Background: To assess whether the clinical outcome of advanced and metastatic renal cell carcinoma (mRCC treated with targeted therapy differs between young and old patients. Patients and methods: A total of 327 patients with advanced renal cell carcinoma and mRCC who received targeted therapy in two Chinese clinical centers were analyzed retrospectively. The patients were stratified into three groups: young (aged <45 years, middle-aged (aged 45–64 years, and old (aged ≥65 years. Overall survival (OS and progression-free survival (PFS curves were drawn using the Kaplan–Meier method, and Cox's proportional hazard regression model was used to compare OS and PFS within age groups. Results: There were no significant differences among young, middle-aged, and old groups in terms of OS (P=0.087, whereas PFS in the old group was significantly better than in the young and middle-aged groups (P=0.043. Both OS and PFS in the younger groups (aged <65 years were significantly worse than in the old group (age ≥65 years; median OS, 28.1 vs 28.7 months [P=0.029]; median PFS, 11.4 vs 14 months [P=0.015]. No difference in OS or PFS was found between the young and middle-aged groups. After adjusting for sex, body mass index, smoking status, hypertension, diabetes mellitus, Eastern Cooperative Oncology Group score, history of cytokines, and Fuhrman grade, old age was an independent favorable prognostic factor for OS and PFS compared with younger age (<65 years (OS, hazard ratio, 0.552 [95

  12. PET/CT-guided percutaneous biopsy of FDG-avid metastatic bone lesions in patients with advanced lung cancer: a safe and effective technique

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Wei; Hao, Bing; Chen, Hao-jun; Zhao, Long; Luo, Zuo-ming; Wu, Hua; Sun, Long [The First Affiliated Hospital of Xiamen University, Department of Nuclear Medicine and Minnan PET Center, Xiamen Cancer Hospital, Xiamen (China)

    2017-01-15

    {sup 18}F-FDG PET/CT should be performed before a diagnostic biopsy site is chosen in patients with a high clinical suspicion of aggressive, advanced tumour. The aim of this study was to evaluate the safety and efficacy of {sup 18}F-FDG PET/CT in guiding biopsy of bone metastases in patients with advanced lung cancer. PET/CT-guided percutaneous core biopsies were performed in 51 consecutive patients with suspected lung cancer and {sup 18}F-FDG-avid bone lesions after whole-body {sup 18}F-FDG PET/CT scans. Generally, one tissue sample was obtained from each patient. The final diagnoses were established on the basis of the histology results. The histopathological and molecular testing results were systematically evaluated. A total of 53 samples were obtained for histological examination or molecular testing as a second biopsy was required in two patients in whom the pathological diagnosis was unclear following the first biopsy. The pathological diagnosis and lung cancer classification were confirmed in 48 patients. The epidermal growth factor receptor mutation status was determined in 23 biopsies, and the mutation rate was 30.4 % (7/23). The anaplastic lymphoma kinase mutation status was determined in 19 biopsies, and the mutation rate was 31.6 % (6/19). Two of the 51 biopsies were positive for non-Hodgkin's lymphoma and one was positive for metastatic renal cell carcinoma. The first-time diagnostic success rate of biopsy was 96.1 % (49/51) and the overall diagnostic success rate and sensitivity were 100 %. All 51 patients were eventually confirmed as having stage IV disease. No serious complications were encountered and the average biopsy time was 30 min. PET/CT-guided percutaneous biopsy of {sup 18}F-FDG-avid bone metastases is an effective and safe method that yields a high diagnostic success rate in the evaluation of hypermetabolic bone lesions in patients with suspected advanced lung cancer. (orig.)

  13. Emerging Molecularly Targeted Therapies in Castration Refractory Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jesal C. Patel

    2013-01-01

    Full Text Available Androgen deprivation therapy (ADT with medical or surgical castration is the mainstay of therapy in men with metastatic prostate cancer. However, despite initial responses, almost all men eventually develop castration refractory metastatic prostate cancer (CRPC and die of their disease. Over the last decade, it has been recognized that despite the failure of ADT, most prostate cancers maintain some dependence on androgen and/or androgen receptor (AR signaling for proliferation. Furthermore, androgen independent molecular pathways have been identified as drivers of continued progression of CRPC. Subsequently, drugs have been developed targeting these pathways, many of which have received regulatory approval. Agents such as abiraterone, enzalutamide, orteronel (TAK-700, and ARN-509 target androgen signaling. Sipuleucel-T, ipilimumab, and tasquinimod augment immune-mediated tumor killing. Agents targeting classic tumorogenesis pathways including vascular endothelial growth factor, hepatocyte growth factor, insulin like growth factor-1, tumor suppressor, and those which regulate apoptosis and cell cycles are currently being developed. This paper aims to focus on emerging molecular pathways underlying progression of CRPC, and the drugs targeting these pathways, which have recently been approved or have reached advanced stages of development in either phase II or phase III clinical trials.

  14. AR-V7 and prostate cancer: The watershed for treatment selection?

    Science.gov (United States)

    Ciccarese, Chiara; Santoni, Matteo; Brunelli, Matteo; Buti, Sebastiano; Modena, Alessandra; Nabissi, Massimo; Artibani, Walter; Martignoni, Guido; Montironi, Rodolfo; Tortora, Giampaolo; Massari, Francesco

    2016-02-01

    The androgen receptor (AR) plays a key role in progression to metastatic castration-resistant prostate cancer (mCRPC). Despite the recent progress in targeting persistent AR activity with the next-generation hormonal therapies (abiraterone acetate and enzalutamide), resistance to these agents limits therapeutic efficacy for many patients. Several explanations for response and/or resistance to abiraterone acetate and enzalutamide are emerging, but growing interest is focusing on importance of AR splice variants (AR-Vs) and in particular of AR-V7. Increasing evidences highlight the concept that variant expression could be used as a potential predictive biomarker and a therapeutic target in advanced prostate cancer. Therefore, understanding the mechanisms of treatment resistance or sensitivity can help to achieve a more effective management of mCRPC, increasing clinical outcomes and representing a promising and engaging area of prostate cancer research.

  15. Intensity of stromal changes is associated with tumor relapse in clinically advanced prostate cancer after castration therapy

    Institute of Scientific and Technical Information of China (English)

    JianPing Wu; WenBin Huang; Hui Zhou; LuWei Xu; JianHua Zhao; JiaGen Zhu; JiangHao Su; HongBin Sun

    2014-01-01

    Reactive stromal changes in prostate cancer(PCa) are likely involved in the emergence of castration‑resistant PCa(CRPC). This study was designed to investigate stromal changes in patients with clinically advanced PCa and analyze their prognostic signiifcance. Prostate needle biopsies obtained from 148patients before castration therapy were analyzed by Masson trichrome staining and immunohistochemical analysis of vimentin and desmin. Reactive stroma grading was inversely correlated with Gleason score. Stroma grade (Masson stain 82.8%vs 45.6%,P<0.001) and vimentin expression(P=0.005) were signiifcantly higher, and desmin expression (P=0.004) signiifcantly lower, in reactive stroma of tumors with a Gleason score of 6–7 than in adjacent peritumoral tissue. Kaplan‑Meier analysis showed a signiifcant association between reactive stroma grade in tumors and the occurrence of CRPC in patients with a Gleason score of 6–7(P=0.009). Furthermore, patients with higher vimentin or lower desmin expression had a shorter disease‑free period. In multivariate analysis, only vimentin expression was a signiifcant predictor of tumor relapse (hazard ratio 1.78, 95% conifdence interval 1.12–10.26,P=0.012). These ifndings indicate that the intensity of reactive stroma is associated with castration responsiveness, especially in patients with a lower Gleason score where the abundant stroma component is most frequently found. High expression of vimentin in tumor stroma was independently associated with poor outcomes in patients with Gleason scores of 6–7, and may serve as a new prognostic marker in daily practice.

  16. Health care costs and utilization of a large insured female population with advanced or metastatic breast cancer by receipt of HER2-targeted agents

    Directory of Open Access Journals (Sweden)

    Meyer N

    2015-04-01

    Full Text Available Nicole Meyer,1 Yanni Hao,2 Pamela Landsman-Blumberg,1 William Johnson,1 Paul Juneau,3 Jaqueline Willemann Rogerio2 1Truven Health Analytics, Cambridge, MA, USA; 2Novartis Pharmaceuticals, East Hanover, NJ, USA; 3Truven Health Analytics, Washington, DC, USA Background: This retrospective administrative claims study of women diagnosed with advanced or metastatic breast cancer compared health care costs by receipt of HER2-targeted agents and by disease stage and age group among patients using HER2-targeted agents. Methods: Women aged ≥18 years and diagnosed with stage III or IV breast cancer were selected from the 2008–2012 Truven Health MarketScan® databases (Truven Health Analytics Inc., Cambridge, MA, USA databases using ICD-9-CM (International Classification of Diseases, 9th Revision, Clinical Modification codes for nondiagnostic medical claims corresponding to breast cancer and local or distant metastases (earliest diagnosis of stage III or stage IV metastasis was designated as the index date. The 12 months prior to the index date were defined as the pre-index period. The post-index period was variable in length, beginning on the index date and continuing through the end of enrolment, inpatient death, or December 31, 2012, whichever occurred first. Receipt of HER2-targeted agents was defined as at least one claim for trastuzumab or lapatinib in the pre-index or post-index period. The study cohorts were women using or not using HER2-targeted agents, women with stage III or IV breast cancer using HER2-targeted agents, and women using HER2-targeted agents and aged 18–44 years, 45–64 years, or 65+ years at index. Health care costs and utilization were calculated on a per patient per month basis for all-cause and breast cancer-related services by place of service. Generalized linear models were used to estimate total all-cause and breast cancer-related costs. Results: A total of 30,660 eligible women met the study selection criteria, 14

  17. Diabetes mellitus and health-related quality of life in prostate cancer: 5-year results from the Prostate Cancer Outcomes Study.

    Science.gov (United States)

    Thong, Melissa S Y; van de Poll-Franse, Lonneke; Hoffman, Richard M; Albertsen, Peter C; Hamilton, Ann S; Stanford, Janet L; Penson, David F

    2011-04-01

    Study Type--Therapy (outcomes research) Level of Evidence 2b. What's known on the subject? and What does the study add? Comorbid diabetes can affect prostate cancer treatment decision-making and outcomes. Few longitudinal studies have investigated the effect of comorbid diabetes on general and cancer-specific health-related quality of life (HRQL) in prostate cancer. Our study found that men with prevalent diabetes (pre-prostate cancer diagnosis) generally had the poorest general HRQL, urinary control and sexual function scores over time, independent of treatment. Non-diabetic men had the best scores and men with incident diabetes (post-prostate cancer diagnosis) reported intermediate scores. OBJECTIVE • To investigate the association between prostate cancer, diabetes, and long-term general and cancer-specific health-related quality of life (HRQL) in a cohort of men with non-metastatic prostate cancer. PATIENTS AND METHODS • We used data from self-administered surveys to assess the HRQL of men with localized or locally advanced disease at 6 (baseline), 12, 24, and 60 months after initial diagnosis. • We examined changes in general and cancer-specific HRQL with repeated measures analyses using a mixed-model approach. RESULTS • In total, we evaluated 1811 men, including 13% with prevalent (pre-prostate cancer diagnosis) diabetes, 12% with incident (post-prostate cancer diagnosis) diabetes, and 75% who never reported being diagnosed with diabetes. • Generally, men with prevalent diabetes had the poorest scores on general HRQL and non-diabetic men the best scores, independent of treatment. • Similarly, men with prevalent diabetes had the lowest urinary control and sexual function scores over time, while men without diabetes had the highest scores. Men with incident diabetes reported intermediate scores. CONCLUSION • Prostate cancer survivors with comorbid diabetes have poorer general and cancer-specific HRQL than those without diabetes.

  18. Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series

    Directory of Open Access Journals (Sweden)

    Mehmet Asim Bilen

    2015-01-01

    Full Text Available Metformin is derived from galegine, a natural ingredient, and recent studies have suggested that metformin could enhance the antitumor effects of hormone ablative therapy or chemotherapy and reduce prostate cancer-specific mortality. Zyflamend is a combination of herbal extracts that reduces inflammation and comprises turmeric, holy basil, green tea, oregano, ginger, rosemary, Chinese goldthread, hu zhang, barberry, and basil skullcap. We propose a maintenance regimen with metformin and/or Zyflamend that targets cancer stem cells and the tumor microenvironment to keep the cancer dormant and prevent it from activation from dormancy. Herein, we report the clinical course of four patients who experienced a clinical response after treatment with metformin and/or Zyflamend.

  19. Prostate Cancer Presenting with Parietal Bone Metastasis

    Science.gov (United States)

    Pare, Abdoul Karim; Abubakar, Babagana Mustapha; Kabore, Moussa

    2017-01-01

    Bone metastases from prostate cancer are very common. They are usually located on the axial skeleton. However, cranial bone metastases especially to the parietal bone are rare. We report a case of metastatic prostate cancer presenting with left parietal bone metastasis in a patient with no urological symptoms or signs. We should consider prostate cancer in any man above 60 years presenting unusual bone lesions.

  20. The Adipocyte-Derived Hormone Leptin Has Proliferative Actions on Androgen-Resistant Prostate Cancer Cells Linking Obesity to Advanced Stages of Prostate Cancer

    Directory of Open Access Journals (Sweden)

    M. Raschid Hoda

    2012-01-01

    Full Text Available Background. Because obesity may be a risk factor for prostate cancer, we investigated proliferative effects of adipocytes-derived hormone leptin on human prostate cancer cells and assessed the role of mitogen-activated protein kinase (MAPK signaling pathway in mediating these actions. Material and Methods. Three human prostate cancer cell lines were treated with increasing doses of recombinant leptin. Cell growth was measured under serum-free conditions using a spectrophotometric assay. Further, Western blotting was applied to detect the phosphorylation of an ERK1/2, and a specific inhibitor of MAPK (PD98059; 40 μM was used. Results. In both androgen-resistant cell lines DU145 and PC-3, cell growth was dose-dependently increased by leptin after 24 hrs and 48 hrs of incubation, whereas leptin’s proliferative effects on androgen-sensitive cell line LNCaP was less pronounced. Further, leptin caused dose-dependent ERK1/2 phosphorylation in both androgen-resistant cell lines, and pretreatment of these cells with PD98059 inhibited these responses. Conclusions. Leptin may be a potential link between obesity and risk of progression of prostate cancer. Thus, studies on leptin and obesity association to prostate cancer should differentiate patients according to androgen sensitivity.

  1. Chemotherapeutic prevention studies of prostate cancer

    DEFF Research Database (Denmark)

    Djavan, Bob; Zlotta, Alexandre; Schulman, Claude

    2004-01-01

    Despite advances in the detection and management of prostate cancer, this disease remains a major cause of morbidity and mortality in men. Increasing attention has focused on the role of chemoprevention for prostate cancer, ie the administration of agents that inhibit 1 or more steps in the natural...... history of prostate carcinogenesis. We review prostate cancer chemoprevention studies in Europe....

  2. Ultrasound Review of Metastatic Lymphadenopathy

    Directory of Open Access Journals (Sweden)

    Sushil Ghanshyam Kachewar

    2013-04-01

    Full Text Available Metastatic Lymphadenopathy is a common occurrence now with the earlier detection possible due to advances in imaging sciences. Although, at times the site of original malignancy is known; there are instances when the primary source of malignancy remains unknown. Ultrasound has the potential to non invasively evaluate the affected lymph nodes. Hence we reviewed the ultrasound findings in all fine needle aspiration cytology proven cases of metastatic lymphadenopathy that presented in the imaging department in the last 12 months. Multiple criteria on Grey Scale ultrasound imaging and on Color Doppler ultrasound imaging were used to label metastatic lymphadenopathy. Round nodes without any matting, presence of intranodal necrosis, intranodal calcifications, increased vascularity and elevated Doppler Pulsatility and Resisitivity Indices were the hallmarks of metastatic lymphadenopathy which enabled correct diagnosis with a sensitivity of 85.25% and a sensitivity of 98.36 %. In our review, the most sensitive and specific criteria was the Roundness Index on Gray scale imaging and Resistance to Perfusion on Color Doppler imaging. This review shows how, ultrasound can satisfactorily diagnose metastatic lymphadenopathy and can therefore be used in the diagnosis as well as follow up of such cases. [Cukurova Med J 2013; 38(2.000: 196-201

  3. Locally advanced prostate cancer: combination of high-dose high-precision radiotherapy and androgen deprivation therapy%Locally advanced prostate cancer:combination of high-dose high-precision radiotherapy and androgen deprivation therapy

    Institute of Scientific and Technical Information of China (English)

    Michel Bolla; René-Olivier Mirimanoff

    2014-01-01

    Locally advanced prostate cancer entails a risk of local,regional and systemic relapse requiring the combination of a Ioco-regional treatment,namely external beam radiotherapy(EBRT) to control the pelvic-confined disease,combined with a systemic therapy,namely androgen-deprivation therapy(ADT),to potentiate irradiation and to destroy the infra-clinical androgen-dependant disease outside the irradiated volume.Many phases Ⅲ randomized trials have paved the way in establishing the indications of this combined approach,which requires a long term ADT(≥2 years) with LHRH agonists.The duration of ADT may be reduced to 6 months should there be a significant comorbidity,a reluctance from the patient or a poor tolerance.A multidisciplinary approach will enable physicians to tailor the treatment strategy and a close cooperation between the specialists and the general practitioners will be set up to prevent as much as possible the side-effects of ADT.

  4. Mandibular metastasis of adenocarcinoma from prostate cancer: case report according to epidemiology and current therapeutical trends of the advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    Juliana Dreyer da Silva de Menezes

    2013-09-01

    Full Text Available Prostate cancer represents the most frequent non-cutaneous neoplasia in males. This type of neoplasia can develop peculiar patterns of evolution, presenting, in many cases, precocious relapses and metastasis. Bone metastasis in the mouth is extremely rare, and represents 1% of all malignant mouth neoplasias. The aim of the present study is to report a clinical case of bone metastasis in the mandibular region associated with a tumoral prostate adenocarcinoma, as well as to discuss connected aspects about diagnosis, prognosis and integrated treatment of this condition.

  5. A changing landscape in castration resistant prostate cancer treatment

    Directory of Open Access Journals (Sweden)

    Alessandra eFelici

    2012-07-01

    Full Text Available Prostate cancer (PC is the leading cause of cancer and the second leading cause of cancer-death among men in the Western world. About 10%-20% of men with PC present with metastatic disease at diagnosis, while 20%-30% of patients diagnosed with localized disease will eventually develop metastases. Although most respond to initial androgen deprivation therapy (ADT, progression to castration resistant PC (CRPC is universal. In 2004 the docetaxel/prednisone regimen was approved for the management of patients with metastatic CRPC, becoming the standard first-line therapy. Recent advances have now led to an unprecedented number of new drug approvals within the past years, providing many new treatment options for patients with metastatic CRPC. Four new drugs have received U.S. Food and Drug Administration (FDA-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. The data supporting the approval of each of these agents are described in this review, as are current approaches in the treatment of metastatic CRPC and ongoing clinical trials of novel treatments and strategies.

  6. Treatment of metastatic bone pain with strontium-89.

    Science.gov (United States)

    Robinson, R G; Spicer, J A; Preston, D F; Wegst, A V; Martin, N L

    1987-01-01

    We have utilized 89Sr as palliative treatment for bone pain secondary to metastatic cancer in the skeleton of over 200 patients. The best results have been in patients with carcinoma of the prostate (80% response rate) and breast (89%). Results in a small number of patients with a variety of other cell types were not nearly as encouraging. Strontium-89 provides excellent palliation in the management of bone pain secondary to prostate and breast carcinoma.

  7. The effects of telomerase inhibition on prostate tumor-initiating cells.

    Science.gov (United States)

    Marian, Calin O; Wright, Woodring E; Shay, Jerry W

    2010-07-15

    Prostate cancer is the most common malignancy in men, and patients with metastatic disease have poor outcome even with the most advanced therapeutic approaches. Most cancer therapies target the bulk tumor cells, but may leave intact a small population of tumor-initiating cells (TICs), which are believed to be responsible for the subsequent relapse and metastasis. Using specific surface markers (CD44, integrin alpha(2)beta(1) and CD133), Hoechst 33342 dye exclusion, and holoclone formation, we isolated TICs from a panel of prostate cancer cell lines (DU145, C4-2 and LNCaP). We have found that prostate TICs have significant telomerase activity which is inhibited by imetelstat sodium (GRN163L), a new telomerase antagonist that is currently in Phase I/II clinical trials for several hematological and solid tumor malignancies. Prostate TICs telomeres were of similar average length to the telomeres of the main population of cells and significant telomere shortening was detected in prostate TICs as a result of imetelstat treatment. These findings suggest that telomerase inhibition therapy may be able to efficiently target the prostate TICs in addition to the bulk tumor cells, providing new opportunities for combination therapies.

  8. Asian trends in primar y androgen depletion therapy on prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Hideyuki Akaza

    2013-01-01

    hTere are notable differences in the incidence and mortality rates for prostate cancer between Asia and Western countries. It is also recognized that there are differences in thinking with regard to treatment options. Recently it is also the case that opinions have been reported concerning the differences between Asian and Western patients with regard to their reaction to androgen depletion therapy (ADT). Given that ADT is a method of treatment that focuses on the elimination of testosterone, an inevitable symptom of its administration is testosterone losing syndrome. It is for this reason that in Western countries ADT has only been recommended in cases of advanced or metastatic cancer. On the other hand, in Asia, ADT is used in relatively many cases, including non-metastatic localized cancer and invasive localized cancer. To date, however, there has been little substantive discussion concerning this difference in utilization of ADT. ADT-related drugs for prostate cancer and the development of new drugs for castration resistant prostate cancer (CRPC) have been actively tested in recent years. It could be the case that analyzing the differences in concepts about ADT between Asia and the West could contribute to the effective use of ADT-related drugs and also help to build new treatment strategies for prostate cancer.

  9. CONSERVATIVE TREATMENT IN LOCALLY AND LOCALLY-ADVANCED PROSTATE CANCER USING CONFORMAL RADIOTHERAPY

    Directory of Open Access Journals (Sweden)

    Tkachev Sergey Ivanovich

    2013-01-01

    Full Text Available The combination of androgen deprivation and radiotherapy increase the probability of diseases full regresses and survival rate. Modern technical and technological opportunities of 3D CRT allow to increase total dose to prostate up to 72-76Gy vs. radiotherapy of 66-70Gy. In this study we compare the rates of post radiation toxicity and the efficiency of treatment for the patients receiving conventional radiotherapy and 3D CRT. The use of 3D CRT has not only result to increase of 10-years recurrence free survival rate from 74% (I grope to 86,5% (II grope, р=0,01, but also to increase of 10-years overall survival, 70% versus 78,4% (р=0,04. The proposed version of conformal 3D CRT radiation therapy made ​​it possible compared to conventional 2D RT radiation therapy by increasing SOD radiation to the tumor, accuracy and compliance with the quality assurance of radiation therapy significantly reduce rates of recurrence and significantly increase the performance of 10-year overall and disease-free survival.

  10. Necessity of re-evaluation of estramustine phosphate sodium (EMP) as a treatment option for first-line monotherapy in advanced prostate cancer.

    Science.gov (United States)

    Kitamura, T

    2001-02-01

    Estramustine phosphate sodium (EMP) was first introduced in the early 1970s for the treatment of prostate cancer, when EMP was supposed to have the dual effect of estrogenic activity and cytotoxicity. For the following decades, it was used mainly in hormone-refractory cases, with a conventional dosage of 4-9 capsules/day, which showed a 30-35% objective response rate. However, a very limited number of cases have been reported that used EMP as a first-line monotherapy in the conventional dosage. One study showed a response rate of 82%, which is at least as effective as conventional estrogen (diethylstilbestrol; DES) monotherapy. Nevertheless, EMP was almost abandoned for the treatment of prostate cancer because of severe adverse side-effects, especially in the cardiovascular system and gastrointestinal tract. Recently, two facts have become evident. First, EMP interferes with cellular microtubule dynamics but does not show alkylating effects. Second, EMP is able to produce a complex with calcium when dairy products are taken concomitantly with EMP, resulting in a decrease in the absorption rate of EMP from the gut. Many clinical trials have been undertaken without warning against concomitant dairy product intake since the introduction of EMP. This fact will jeopardize almost all the clinical trials performed before 1990. It is considered that response rates have been underestimated and better results could have been obtained because side-effects decrease dose-dependently. Low-dose EMP monotherapy (2 capsules/day) has been performed infrequently in previously untreated advanced prostate cancer. The only large trial by the European Organization for Research and Treatment of Cancer in 1984 was biased in selecting patients. Nevertheless, the response rate of EMP is comparable to that of DES. In this study, the adverse side-effects of EMP were less than that of DES. Recently, a study was conducted at the University of Tokyo of 11 patients with advanced prostate cancer on

  11. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kiessling, Andrea [Biologics Safety and Disposition, Preclinical Safety, Translational Sciences, Novartis Institutes for BioMedical Research, Novartis Pharma AG, Werk Klybeck, Klybeckstraße 141, Basel CH-4057 (Switzerland); Wehner, Rebekka [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Füssel, Susanne [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Bachmann, Michael [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Wirth, Manfred P. [Department of Urology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany); Schmitz, Marc, E-mail: marc.schmitz@tu-dresden.de [Institute of Immunology, Medical Faculty, University of Technology Dresden, Fetscherstraße 74, Dresden 01307 (Germany)

    2012-02-22

    Prostate cancer (PCa) is the most common noncutaneous cancer diagnosis and the second leading cause of cancer-related deaths among men in the United States. Effective treatment modalities for advanced metastatic PCa are limited. Immunotherapeutic strategies based on T cells and antibodies represent interesting approaches to prevent progression from localized to advanced PCa and to improve survival outcomes for patients with advanced disease. CD8{sup +} cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4{sup +} T cells augment the antigen-presenting capacity of dendritic cells and promote the expansion of tumor-reactive CTLs. Antibodies mediate their antitumor effects via antibody-dependent cellular cytotoxicity, activation of the complement system, improving the uptake of coated tumor cells by phagocytes, and the functional interference of biological pathways essential for tumor growth. Consequently, several tumor-associated antigens (TAAs) have been identified that represent promising targets for T cell- or antibody-based immunotherapy. These TAAs comprise proteins preferentially expressed in normal and malignant prostate tissues and molecules which are not predominantly restricted to the prostate, but are overexpressed in various tumor entities including PCa. Clinical trials provide evidence that specific immunotherapeutic strategies using such TAAs represent safe and feasible concepts for the induction of immunological and clinical responses in PCa patients. However, further improvement of the current approaches is required which may be achieved by combining T cell- and/or antibody-based strategies with radio-, hormone-, chemo- or antiangiogenic therapy.

  12. Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy.

    Science.gov (United States)

    O'Neill, Daniel; Jones, Dominic; Wade, Mark; Grey, James; Nakjang, Sirintra; Guo, Wenrui; Cork, David; Davies, Barry R; Wedge, Steve R; Robson, Craig N; Gaughan, Luke

    2015-09-22

    The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated AR(W741L/C) mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of AR(W741L) highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, AR(W741L) transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients.

  13. Mono-2-ethyhexyl phthalate advancing the progression of prostate cancer through activating the hedgehog pathway in LNCaP cells.

    Science.gov (United States)

    Yong, Wang; Jiao, Chen; Jianhui, Wu; Yan, Zhao; Qi, Pan; Xiu, Wang; Zuyue, Sun; Yunhui, Zhang

    2016-04-01

    Hedgehog (Hh) pathway plays a critical role in the progression of prostate cancer (PCa), the most commonly diagnosed non-cutaneous cancer in male adults. Studies showed that di-n-butyl phthalate (DBP) could interference with the Hh pathway. Di-2-ethylhexyl phthalate (DEHP), the congener of DBP, is the major plasticizer used in plastic materials that are inevitably exposed by patients with PCa. The aim of this in vitro study was to investigate whether mono-2-ethyhexyl phthalate (MEHP, the active metabolite of DEHP) could activate the Hh pathway of LNCaP cells. Results showed that the expression of the critical gene of Hh pathway PTCH and androgen-regulated gene KLK3 was significantly decreased on 3, 6 and 9 days with Hh pathway inhibitor cyclopamine's treatment. MEHP notably up-regulated the expression of PTCH with a dose-response relationship in the presence of cyclopamine, which indicate that MEHP might target on the downstream components of Hh pathway and advance the progression of PCa through activating the Hh pathway.

  14. Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer.

    Science.gov (United States)

    Foley, Christopher; Mitsiades, Nicholas

    2016-04-01

    Medical or surgical castration serves as the backbone of systemic therapy for advanced and metastatic prostate cancer, taking advantage of the importance of androgen signaling in this disease. Unfortunately, resistance to castration emerges almost universally. Despite the development and approval of new and more potent androgen synthesis inhibitors and androgen receptor (AR) antagonists, prostate cancers continue to develop resistance to these therapeutics, while often maintaining their dependence on the AR signaling axis. This highlights the need for innovative therapeutic approaches that aim to continue disrupting AR downstream signaling but are orthogonal to directly targeting the AR itself. In this review, we discuss the preclinical research that has been done, as well as clinical trials for prostate cancer, on inhibiting several important families of AR-interacting proteins, including chaperones (such as heat shock protein 90 (HSP90) and FKBP52), pioneer factors (including forkhead box protein A1 (FOXA1) and GATA-2), and AR transcriptional coregulators such as the p160 steroid receptor coactivators (SRCs) SRC-1, SRC-2, SRC-3, as well as lysine deacetylases (KDACs) and lysine acetyltransferases (KATs). Researching the effect of-and developing new therapeutic agents that target-the AR signaling axis is critical to advancing our understanding of prostate cancer biology, to continue to improve treatments for prostate cancer and for overcoming castration resistance.

  15. Prostate Cancer Immunotherapy with Sipuleucel-T: Current Standards and Future Directions.

    Science.gov (United States)

    Wei, Xiao X; Fong, Lawrence; Small, Eric J

    2015-01-01

    The management of advanced prostate cancer, specifically metastatic castrate-resistant prostate cancer (mCRPC), remains a therapeutic challenge. Sipuleucel-T (Provenge; APC8015) was approved by the FDA in 2010 for the treatment of asymptomatic or minimally symptomatic mCRPC patients, and it remains the only FDA-approved immunotherapy for prostate cancer of any indication to date. Given the continued need to improve therapeutics in patients with advanced prostate cancer, as well as recent enthusiasm for cancer immunotherapy, there is a wide range of ongoing trials evaluating combinations of sipuleucel-T with other therapeutics. Additional trials are aiming to expand the application of sipuleucel-T to prostate cancer patients beyond the mCRPC setting. Ongoing challenges include understanding the full mechanism of action of sipuleucel-T, optimizing the sequence of sipuleucel-T in relation to other therapies for mCRPC in clinical practice, and the identification of surrogate markers to predict survival benefit in clinical trials.

  16. 前列腺癌组织中雄激素受体剪接变异体7的表达对转移性前列腺癌患者总生存的影响%Impact of AR-V7 expression on overall survival for patients with metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    瞿元元; 叶定伟; 戴波; 孔蕴毅; 常坤; 顾成元; 孙自捷; 张海梁; 朱耀

    2014-01-01

    Objective To investigate the impact of androgen receptor splice variant 7 (AR-V7) expression on overall survival for patients with metastatic prostate cancer.Methods The data of 113 diagnosed metastatic prostate cancer patients from January 2002 to June 2010 were collected retrospectively,including patient's age at diagnosis,prostate-specific antigen (PSA) level at diagnosis,Gleason score,clinical stage,PSA nadir during hormonal therapy,the time to PSA nadir,vital status,survival time and cause of death.The expression of AR-V7 in prostate cancer tissue was detected by using immunohistochemical staining.The correlation of AR-V7 expression and patient clinicopathological characteristics in all patients were analysed using Student t-test or Chi-square test.Cox proportional hazards regression models were used to evaluate the predictive role of AR-V7 expression and patient characteristics for overall survival.Results The median PSA nadir was 0.7 μg/L (ranged from 0.0 to 143.0 μg/L).The median time to PSA nadir was 8.1 months (ranged from 0.9 to 71.0 months).The follow-up was performed until March 12,2014.During the follow-up period,67 of 113 metastatic prostate cancer patients (59.3%) died and the median overall survival was 96 months (ranged from 5 to 135 months).The AR-V7 detection rate was 20.4% (23/113).The serum PSA level in patients with positively expression of AR-V7 was significantly higher than that without AR-V7 expression (t =2.521,P =0.013).Multivariate Cox regression analysis indicated that the expression of AR-V7 (HR =2.421,P =0.002) and time to PSA nadir (HR =1.019,P =0.022) were independent prognostic factors of overall survival for metastatic prostate cancer patients.Conclusions The expression of AR-V7 in prostate cancer tissues and time to PSA nadir during hormonal therapy are independent prognostic factors of overall survival for metastatic prostate cancer patients.Therapy targeting AR-V7 may improve prognosis of metastatic prostate cancer

  17. Prostate Ultrasound

    Medline Plus

    Full Text Available ... as detailed as with the transrectal probe. An MRI of the pelvis may be obtained as an ... Benign Prostatic Hyperplasia (BPH) Prostate Cancer Ultrasound- and MRI-Guided Prostate Biopsy Images related to Ultrasound - Prostate ...

  18. Prostate Ultrasound

    Science.gov (United States)

    ... News Physician Resources Professions Site Index A-Z Ultrasound - Prostate Ultrasound of the prostate uses sound waves ... the limitations of Prostate Ultrasound Imaging? What is Ultrasound Imaging of the Prostate? Ultrasound is safe and ...

  19. Targeting the Aberrant Androgen Receptor in Advanced Treatment Resistant Prostate Cancer

    Science.gov (United States)

    2014-10-01

    effectively disrupt the lethal mitotic phenotype; ii) the AR-V-driven transcriptome can provide biomarkers to identify patients at risk for progression and...as AR-FL will effectively disrupt the lethal mitotic phenotype and thereby improve the prognosis of patients with advanced CRPC; ii) the transcriptome

  20. Health Resource Utilization Associated with Skeletal-Related Events in Patients with Advanced Prostate Cancer: A European Subgroup Analysis from an Observational, Multinational Study

    Directory of Open Access Journals (Sweden)

    Amit Bahl

    2014-07-01

    Full Text Available This study aimed to increase the understanding of health resource utilization (HRU associated with skeletal-related events (SREs occurring in patients with bone metastases secondary to advanced prostate cancer. A total of 120 patients from Germany, Italy, Spain and the United Kingdom were enrolled in this observational study. They had bone metastases secondary to prostate cancer and had experienced at least one SRE in the 97 days before giving informed consent. HRU data were collected retrospectively for 97 days before enrolment and prospectively for up to 18–21 months. HRU, including the number and duration of inpatient hospitalizations, number of outpatient and emergency department visits and procedures, was independently attributed by investigators to an SRE. Of the 222 SREs included in this analysis, 26% were associated with inpatient stays and the mean duration per SRE was 21.4 days (standard deviation (SD 17.8 days. Overall, 174 SREs (78% required an outpatient visit and the mean number of visits per SRE was 4.6 (SD 4.6. All SREs are associated with substantial HRU. Preventing SREs in patients with advanced prostate cancer and bone metastases may help to reduce the burden to both patients and European healthcare systems.