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Sample records for advanced metastatic prostate

  1. 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....

  2. [Medical castration in the treatment of locally advanced or metastatic prostate cancer: an update].

    Science.gov (United States)

    Drouin, S-J; Rouprêt, M; Davin, J-L; Soulié, M

    2009-04-01

    Indications for hormonotherapy in prostate cancer are in deep mutation and are constantly evolving. Used initially (1941) in metastatic stages, hormone therapy is used nowadays in locally advanced prostate cancer and aggressive localized disease. Its prescription in association with radiotherapy or surgery has provided a benefit regarding survival free progression. The place of hormone therapy in localized prostate cancer is not well defined and the debate is still ongoing, especially in case of biochemical recurrence after irradiation or radical prostatectomy and even in neoadjuvant cases. Additional and further studies are ongoing and are strongly needed to establish new guidelines. Nevertheless, hormone therapy is not restricted any more to palliative cases and is part of the current therapeutic arsenal of the urologist for high risk localized and/or locally advanced prostate cancers. PMID:19465332

  3. Pharmacoeconomics of Available Treatment Options for Metastatic Prostate Cancer

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    Zeliadt, Steven B.; Penson, David F.

    2007-01-01

    The resources devoted to managing metastatic prostate cancer are enormous, yet little attention has been given to directly measuring the economic consequences of treatment alternatives. The purpose of this article was to evaluate the pharmacoeconomics of available treatments for metastatic prostate cancer, including hormone-sensitive disease, androgen-independent prostate cancer and locally advanced/progressive disease. We identified 58 articles addressing economic issues related to metastati...

  4. Upfront Chemotherapy for Metastatic Prostate Cancer.

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    Lam, Elaine T; Flaig, Thomas W

    2015-12-01

    Traditionally, androgen deprivation therapy (ADT) has been the standard initial treatment for metastatic hormone-sensitive prostate cancer (mHSPC), with chemotherapy utilized in the castration-resistant setting. Data reported from three recent clinical trials shed new light on the role of upfront docetaxel in advanced or mHSPC. Two of these studies-CHAARTED and STAMPEDE-showed significant improvement in overall survival, while the third study, GETUG-AFU 15, showed no statistical difference. The CHAARTED study showed a 13.6-month survival improvement and the STAMPEDE study showed a 10-month survival improvement with ADT plus docetaxel, compared with ADT alone, in the hormone-sensitive setting. These numbers are remarkable when compared with the 2.9-month survival benefit from docetaxel in the metastatic castration-resistant setting, which has been the standard setting for the use of docetaxel in advanced prostate cancer. In this review, we describe the historical data for chemotherapy in the perioperative and metastatic prostate cancer settings, and the recent trials that are changing the paradigm in support of docetaxel in the upfront setting. PMID:26676900

  5. Treatment of Metastatic Prostate Cancer in Older Adults.

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    Loh, Kah Poh; Mohile, Supriya G; Kessler, Elizabeth; Fung, Chunkit

    2016-10-01

    The aging of the population, along with rising life expectancy, means that increasing numbers of older men will be diagnosed with prostate cancer, and a large proportion of these men will present with metastatic disease. In this paper, we discuss recent advances in prostate cancer treatment. In particular, we review management approaches for older patients with metastatic prostate cancer based on the decision tree developed by the International Society of Geriatric Oncology, which categorized older men as "fit," "vulnerable," and "frail" according to comprehensive geriatric assessment. PMID:27586377

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

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    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

  7. Abiraterone Improves Survival in Metastatic Prostate Cancer

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    A multinational phase III trial found that the drug abiraterone acetate prolonged the median survival of patients with metastatic castration-resistant prostate cancer by 4 months compared with patients who received a placebo.

  8. 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

  9. 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

    DEFF Research Database (Denmark)

    Martínez-Piñeiro, Luis; Schalken, Jack A; Cabri, Patrick;

    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...... change at 6 months, according to baseline variables. Other outcome measures included urinary PCA3 and TMPRSS2-ERG scores and statuses, and serum testosterone and prostate-specific antigen (PSA) levels at baseline and at 1, 3 and 6 months after initiation of ADT. Safety was assessed by recording adverse...... metastasis or unknown metastasis status. TMPRSS2-ERG scores ≥35 were considered positive (n = 149 [51.6%]). Age, presence of metastasis, PSA level and Gleason score at baseline were not associated with a significant difference in the proportion of TMPRSS2-ERG-positive scores. The median serum PSA levels...

  10. 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...

  11. [Metastatic hormone-sensitive prostate cancer].

    Science.gov (United States)

    Gravis, Gwenaelle; Salem, Naji; Walz, Jochen

    2015-01-01

    The prostate cancer in its hormone-sensitive metastatic presentation is infrequent, it is either an initial presentation of the disease or an evolution after local treatment, without castration of the biological relapse. The surgical or biological castration remains the cornerstone of the treatment. The deadline of castration initiation and its modalities of administration, intermittent or continuous rest debated but consensual on the initiation is the appearance of the symptomatic disease. The chemotherapy by docetaxel in association with the castration increases significantly the survival of the patients having a high tumoral volume. The efficacy on the whole metastatic population requires additional analyses. Clinical prognostic factors as the bone localizations (axial or appendicular), the visceral involvement (liver, lung) are determining for the survival of these patients. Biological prognostic factors are in evaluation. Except the clodronate acid, which showed a survival improvement in the hormone-sensitive metastatic prostate cancer (HSMPC), the other treatments targeting the bone (zoledronic acid, rank-ligand inhibitor) demonstrated a benefit only in castrate resistant metastatic prostate cancer (MCRPC). The management of local disease lets suggest a benefit to at least symptomatic disease, but it requires to be estimated prospectively in clinical trials. The new hormonal treatments targeting the androgen receptor in CPMRC are in evaluation in CPMHS. The objective is to increase the survival and the quality of life of the CPMHS and to delay the evolution towards the castration resistant metastatic disease. PMID:25609491

  12. 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.

  13. 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

  14. Management of Hormone-Sensitive and Hormone-Refractory Metastatic Prostate Cancer.

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    Rago

    1998-11-01

    BACKGROUND: Prostate cancer is a significant health problem in the United States and is the focus of increasing attention in our society. With the aging of the US population, it is likely that prostate cancer will continue to grow in importance. The options for systemic therapy of metastatic prostate cancer should be familiar to physicians, including nonspecialists, whose patients seek their advice and counsel. METHODS: Past and recent literature was surveyed to provide an understanding of the systemic treatment of advanced prostate cancer. The author presents a review of the systemic treatment of metastatic prostate cancer in different clinical circumstances and addresses the current status of chemotherapy in the management of advanced prostate cancer. RESULTS: Early androgen deprivation used over prolonged periods appears to be modestly superior to delayed androgen deprivation with a small potential survival advantage and an advantage in delaying disease progression in advanced prostate cancer. Patients with hormone-refractory prostate cancer may benefit from secondary hormonal therapy (eg, adrenal enzyme inhibitors, antiandrogens, glucocorticoids) and chemotherapy. CONCLUSIONS: The choices of therapy for metastatic prostate cancer depend on individual patient preference. Patients and physicians should be aware of the possible side effects associated with the therapeutics options for treatment of metastatic prostate cancer. PMID:10761100

  15. 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.

  16. 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.

  17. Predictors of Metastatic Disease After Prostate Brachytherapy

    International Nuclear Information System (INIS)

    Purpose: To identify predictors of metastatic disease after brachytherapy treatment for prostate cancer. Methods and Materials: All patients who received either brachytherapy alone (implant) or brachytherapy in combination with external beam radiation therapy for treatment of localized prostate cancer at The Mount Sinai Hospital between June 1990 and March 2007 with a minimum follow-up of 2 years were included. Univariate and multivariable analyses were performed on the following variables: risk group, Gleason score (GS), clinical T stage, pretreatment prostate-specific antigen level, post-treatment prostate-specific antigen doubling time (PSA-DT), treatment type (implant vs. implant plus external beam radiation therapy), treatment era, total biological effective dose, use of androgen deprivation therapy, age at diagnosis, and race. PSA-DT was analyzed in the following ordinate groups: 0 to 90 days, 91 to 180 days, 180 to 360 days, and greater than 360 days. Results: We included 1,887 patients in this study. Metastases developed in 47 of these patients. The 10-year freedom from distant metastasis (FFDM) rate for the entire population was 95.1%. Median follow-up was 6 years (range, 2–15 years). The only two significant predictors of metastatic disease by multivariable analyses were GS and PSA-DT (p < 0.001 for both variables). Estimated 10-year FFDM rates for GS of 6 or less, GS of 7, and GS of 8 or greater were 97.9%, 94.3%, and 76.1%, respectively (p < 0.001). Estimated FFDM rates for PSA-DT of 0 to 90 days, 91 to 180 days, 181 to 360 days, and greater than 360 days were 17.5%, 67.9%, 74%, and 94.8%, respectively (p < 0.001). Estimated 10-year FFDM rates for the low-, intermediate-, and high-risk groups were 98.6%, 96.2%, and 86.7%, respectively. A demographic shift to patients presenting with higher-grade disease in more recent years was observed. Conclusions: GS and post-treatment PSA-DT are both statistically significant independent predictors of metastatic

  18. 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.

  19. Intermittent versus continuous androgen deprivation for locally advanced, recurrent or metastatic prostate cancer: a systematic review and meta-analysis

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    Botrel, Tobias Engel Ayer; Clark, Otávio; dos Reis, Rodolfo Borges; Pompeo, Antônio Carlos Lima; Ferreira, Ubirajara; Sadi, Marcus Vinicius; Bretas, Francisco Flávio Horta

    2014-01-01

    Background Prostate cancer is the most common cancer in older men in the United States (USA) and Western Europe. Androgen deprivation (AD) constitutes, in most cases, the first-line of treatment for these cases. The negative impact of CAD in quality of life, secondary to the adverse events of sustained hormone deprivation, plus the costs of this therapy, motivated the intermittent treatment approach. The objective of this study is to to perform a systematic review and meta-analysis of all ran...

  20. Management of metastatic hormone-sensitive prostate cancer.

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    Bernard, Brandon; Sweeney, Christopher J

    2015-03-01

    In 2014, prostate cancer will affect roughly 15 % of American men during their lifetimes with about 230,000 new cases and 29,000 deaths per year. If required, most can be treated with curative surgery or radiotherapy. Upon relapse, androgen deprivation therapy (intermittent or continuous) is the cornerstone of treatment for hormone-sensitive disease. Response is variable and treatment is associated with a significant risk of toxicity. Recently, significant advances in survival have been demonstrated with chemohormonal therapy in men with high-volume disease. In addition, new findings have informed the approach to preventing bone complications in patients on therapy for metastatic hormone-sensitive prostate cancer. Devising clinical prediction tools and biomarkers is needed to select patients most likely to benefit from certain therapies and allow for a personalized approach. PMID:25677237

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Systemic therapy for the treatment of hormone-sensitive metastatic prostate cancer: from intermittent androgen deprivation therapy to chemotherapy.

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    Liaw, Bobby C; Shevach, Jeffrey; Oh, William K

    2015-03-01

    Treatment of advanced prostate cancer has changed considerably in recent years, but the vast majority of advances have been made in patients with metastatic castration-resistant disease. There have been relatively fewer advances in the earlier, hormonally responsive stage of metastatic disease. Since the empiric establishment of androgen deprivation therapy as first-line therapy for metastatic prostate cancer decades ago, there have been multiple studies looking at variations of suppressing testosterone, but the overall paradigm has not been strongly challenged until more recently. In particular, the dramatic results reported by the CHAARTED trial not only bring chemotherapy to an arena historically dominated solely by hormonal therapy but also stimulate renewed efforts into improving upon our management of metastatic hormone-sensitive prostate cancer. PMID:25677235

  7. 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.

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

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

    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 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 (pprostate 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. PMID:25859981

  9. Enzalutamide for patients with metastatic castration-resistant prostate cancer

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    Ramadan, Wijdan H; Kabbara, Wissam K; Al Basiouni Al Masri, Hiba S

    2015-01-01

    Objective To review and evaluate current literature on the US Food and Drug Administration (FDA)-approved drug enzalutamide (XTANDI®) in metastatic castration-resistant prostate cancer. Data sources Literature search was done through PubMed using the terms enzalutamide, MDV3100, abiraterone, and castration-resistant prostate cancer. Data from FDA product labels were also used. Study selection and data extraction Recent and relevant studies were included in the review. Collected clinical trials were screened and evaluated. Data synthesis Enzalutamide is an androgen receptor (AR) inhibitor with high selectivity and affinity to the AR. It was approved by the FDA to treat metastatic castration-resistant prostate cancer in patients previously treated with docetaxel, after a Phase III trial (AFFIRM) that showed a 4.8-month survival benefit in this population. Recently, the FDA expanded the approval of enzalutamide as first-line therapy for metastatic castration-resistant prostate cancer (mCRPC) who did not receive chemotherapy. Moreover, enzalutamide is shown to be associated with an acceptable safety profile. Conclusion Enzalutamide has been shown to be both safe and effective in improving overall survival in metastatic castration-resistant prostate cancer postchemotherapy with docetaxel and as a first line treatment before initiation of chemotherapy. However, additional studies and head-to-head trials are needed. PMID:25945058

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

    OpenAIRE

    Ibrahim Zardawi; Peter Chong

    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.

  11. 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.

  12. 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.

  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. Metastatic Breast Carcinoma to the Prostate Gland

    Science.gov (United States)

    Kapp, Meghan E.

    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. PMID:27429817

  15. 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.

  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. Management of hormone-sensitive metastatic prostate cancer.

    Science.gov (United States)

    Agarwal, Neeraj; Hussain, Maha

    2013-12-01

    Targeting gonadal androgen synthesis (often in conjunction with blockade of androgen receptor) is the cornerstone of treatment of hormone-sensitive metastatic prostate cancer (HSPC). Despite the failure of androgen deprivation therapy, most tumors maintain some dependence on androgen or androgen receptor signaling for proliferation. This article reviews the current standard of care for metastatic HSPC, mechanisms of treatment resistance, novel drugs targeting the androgen signaling pathway, biomarkers predicting response to treatment and survival, future directions, and ongoing clinical trials in HSPC. PMID:24188260

  18. 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.

  19. Metastatic Prostate Adenocarcinoma Presenting Central Diabetes Insipidus

    OpenAIRE

    Hakkı Yılmaz; Mustafa Kaya; Mücteba Can; Mustafa Özbek; Bahir Keyik

    2012-01-01

    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 patie...

  20. [Treatment strategies for advanced prostate cancer].

    Science.gov (United States)

    Küronya, Zsófia; Bíró, Krisztina; Géczi, Lajos; Németh, Hajnalka

    2015-09-01

    There has been dramatic improvement in the diagnosis and treatment of prostate cancer recently. The treatment of localized disease became more successful with the application of new, sophisticated techniques available for urologic surgeons and radiotherapists. Nevertheless a significant proportion of patients relapses after the initial local treatment or is diagnosed with metastatic disease at the beginning. In the past five years, six new drugs became registered for the treatment of metastatic, castration-resistant prostate cancer, such as sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, the α-emitting radionuclide alpharadin and the receptor activator of nuclear factor kappa-B (RANK) ligand inhibitor denosumab. The availability of these new treatment options raises numerous questions. In this review we present the standard of care of metastatic prostate cancer by disease stage (hormone naive/ hormone sensitive metastatic prostate cancer, non-metastatic castration-resistant prostate cancer, oligometastatic/multimetastatic castration-resistant prostate cancer) and the emerging treatment modalities presently assessed in clinical trials. We would also like to give advice on debatable aspects of the management of metastatic prostate cancer. PMID:26339912

  1. Radium-223 for Advanced Prostate Cancer

    Science.gov (United States)

    A summary of results from a phase III trial that compared radium-223 dichloride plus the best standard of care versus a placebo plus the best standard of care in men with metastatic, castration-resistant prostate cancer.

  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. [Advancement in the treatment against prostate cancer].

    Science.gov (United States)

    Shinohara, Nobuo; Abe, Takashige; Maruyama, Satoru

    2016-01-01

    With the advancement of basic science and medical technology, the treatment against prostate cancer (PC) has dramatically changed. Although the introduction of robotic radical prostatectomy and particle therapies in patients with early stage PC is of much note, the issues on the over-treatment and treatment cost should be heeded. From these points, active surveillance has been an important strategy in these patients. In patients with metastatic hormone-sensitive PC, especially high volume metastases, androgen deprivation therapy (ADT) with docetaxel has been reported to prolong overall survival compared with ADT alone. Lastly, several novel therapeutic agents have been investigated and shown to be favorable outcomes in patients with castration resistant PC. This review focuses on the recent advancement in the treatment against PCs. PMID:26793875

  4. Prostate-Specific Antigen Nadir and Time to Prostate-Specific Antigen Nadir Following Maximal Androgen Blockade Independently Predict Prognosis in Patients with Metastatic Prostate Cancer

    OpenAIRE

    Hong, Seok Young; Cho, Dae Sung; Kim, Sun Il; Ahn, Hyun Soo; Kim, Se Joong

    2012-01-01

    Purpose To evaluate the influence of prostate-specific antigen (PSA) kinetics following maximal androgen blockade (MAB) on disease progression and cancer-specific survival in patients with metastatic, hormone-sensitive prostate cancer. Materials and Methods One hundred thirty-one patients with metastatic, hormone-sensitive prostate cancer treated with MAB at our institution were included in this study. Patients' characteristics, PSA at MAB initiation, PSA nadir, time to PSA nadir (TTN), and P...

  5. Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: results from the STAMPEDE and CHAARTED trials.

    Science.gov (United States)

    van Soest, Robert J; de Wit, Ronald

    2015-01-01

    Androgen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), following robust, albeit modest, survival benefit in two randomized phase 3 trials. The recently published CHAARTED trial was the first to show that combining ADT with docetaxel in men with hormone-naïve (hormone-sensitive) metastatic prostate cancer (mHSPC) yielded a remarkable overall survival benefit of 13.6 months as compared with ADT alone. In the current issue of The Lancet, James et al. report results of the STAMPEDE trial in men with high-risk locally advanced or metastatic prostate cancer initiating long-term hormone therapy. The combination of six cycles of docetaxel with ADT in men commencing long-term ADT demonstrated a similar OS benefit compared with standard of care (SOC) by a median of 10 months. Based on the consistency of the data and the firmness of the benefit provided, docetaxel in addition to ADT should be considered SOC for men with newly diagnosed mHSPC. PMID:26695172

  6. 'Charting a new course for prostate cancer' - currying favor for docetaxel in hormone-sensitive metastatic prostate cancer.

    Science.gov (United States)

    Voskoboynik, Mark; Staffurth, John; Malik, Zafar; Sweeney, Christopher; Chowdhury, Simon

    2014-11-01

    Docetaxel has an established role in the treatment of metastatic castrate-resistant prostate cancer. A number of recent treatments have been shown to improve the survival outcomes for this group of patients and many with improved toxicity profiles, bringing the role of docetaxel into question. We discuss the results and implications of the CHAARTED study that demonstrated a significant improvement in overall survival with docetaxel in metastatic hormone-sensitive prostate cancer. PMID:25353342

  7. A transgenic mouse model of metastatic prostate cancer originating from neuroendocrine cells

    OpenAIRE

    Garabedian, Emily M.; Humphrey, Peter A.; Jeffrey I Gordon

    1998-01-01

    A transgenic mouse model of metastatic prostate cancer has been developed that is 100% penetrant in multiple pedigrees. Nucleotides −6500 to +34 of the mouse cryptdin-2 gene were used to direct expression of simian virus 40 T antigen to a subset of neuroendocrine cells in all lobes of the FVB/N mouse prostate. Transgene expression is initiated between 7 and 8 weeks of age and leads to development of prostatic intraepithelial neoplasia within a week. Prostatic intraepithelial neoplasia progres...

  8. Prostate Cancer Stem Cells: Research Advances

    OpenAIRE

    Dagmara Jaworska; Wojciech Król; Ewelina Szliszka

    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 th...

  9. Why Chemotherapy Should be Given Early for Men with Metastatic Prostate Cancer.

    Science.gov (United States)

    Hernandez-Aya, Leonel F; Hussain, Maha

    2015-01-01

    Metastatic hormone-sensitive prostate cancer (mHSPC) is an incurable disease, and despite a high response rate to androgen-deprivation therapy (ADT), outcomes have not significantly changed for many decades. Earlier attempts at multitargeted strategies with the addition of cytotoxic chemotherapy to ADT did not affect survival. As more effective therapies are emerging, including cytotoxic therapy for patients with metastatic castrate-resistant prostate cancer (mCRPC), there is increasing interest for testing these drugs earlier in the disease course. The premise is that agents with clinical benefit in advanced mCRPC may have a better effect if used preemptively before the development of significant resistance and to attack earlier de novo androgen resistant/independent clones. The recent results of the phase III clinical trial E3805 investigating ADT with or without docetaxel in mHSPC provide compelling support for this strategy. Docetaxel combined with ADT significantly improved overall survival from 44 to 57.6 months (p=0.0003), particularly in patients with high-volume disease (from 32.2 to 49.2 months; p=0.0006). Longer follow-up is needed to assess the effect on patients with low disease burden. Further studies are needed to further maximize the antitumor effect in patients with mHSPC and to investigate the effects of advancing therapy to this disease setting on the efficacy of respective agents in the castration-resistant setting. PMID:25993184

  10. The management of localized and locally advanced prostate cancer - 1995

    International Nuclear Information System (INIS)

    Purpose/Objectives: The intent of this course is to review the issues involved in the management of non-metastatic adenocarcinoma of the prostate. - The value of pre-treatment prognostic factors including stage, grade and PSA value will be presented, and their value in determining therapeutic strategies will be discussed. - Controversies involving the simulation process and treatment design will be presented. The value of CT scanning, Beams-Eye View, 3-D planning, intravesicle, intraurethral and rectal contrast will be presented. The significance of prostate and patient movement and strategies for dealing with them will be presented. - The management of low stage, low to intermediate grade prostate cancer will be discussed. The dose, volume and timing of irradiation will be discussed as will the role of neo-adjuvant hormonal therapy, neutron irradiation and brachy therapy. The current status of radical prostatectomy and cryotherapy will be summarized. - Treatment of locally advanced, poorly differentiated prostate cancer will be presented including a discussion of neo-adjuvant and adjuvant hormones, dose-escalation and neutron irradiation. - Strategies for post-radiation failures will be presented including data on cryotherapy, salvage prostatectomy and hormonal therapy (immediate, delayed and/or intermittent). New areas for investigation will be reviewed. - The management of patients post prostatectomy will be reviewed. Data on adjuvant radiation and therapeutic radiation for biochemical or clinically relapsed patients will be presented. This course hopes to present a realistic and pragmatic overview for treating patients with non-metastatic prostatic cancer

  11. 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

  12. 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.

  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. PMID:27357679

  14. Radiotherapy in the management of non-metastatic prostate cancer: Current standards and future opportunities

    International Nuclear Information System (INIS)

    Objectives: The intent of this course is to review issues involved in the management of non-metastatic prostate cancer and to clarify the role of external beam radiotherapy, the use of neo-adjuvant and adjuvant hormonal therapy in conjunction with the radiation, the management of patients with regional metastases and recurrent disease following surgery and radiation. At the end of this course, participants should be able to fluently discuss management issues and strategies across the entire spectrum of non-metastatic prostate cancer. - Pre-treatment prognostic factors including clinical stage, grade, and pre-treatment PSA, will be presented and their relative value in determining therapeutic strategies will be discussed. Strategies to be discussed include standard dose radiation, escalated dose radiation, particle radiation and the use of adjuvant and neo-adjuvant hormonal therapy. - The process of simulation and field design will be presented, the value of CT-based treatment planning, beams-eye view design and the relative value of three-dimensional treatment planning will be discussed. - The significance of prostate and patient movement and strategies for dealing with this will also be presented so that what constitutes an adequate simulation and margin of treatment can be clarified. - The management of newly diagnosed patients, covering the range of low stage/low grade to locally advanced prostate cancer will be discussed. - The relative value of increasing dose, the relative value of using neo-adjuvant and/or adjuvant hormone therapy and the indications for escalated dose will be presented. - Strategies for managing post-prostatectomy patients will be reviewed. Data on adjuvant and therapeutic irradiation for biochemical failure will be presented and a strategy for management will be discussed. - How to deal with patients with residual disease post radiation will be discussed and the relative value of cryotherapy, salvage prostatectomy or hormonal therapy will

  15. 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

  16. Predictive computational modeling to define effective treatment strategies for bone metastatic prostate cancer.

    Science.gov (United States)

    Cook, Leah M; Araujo, Arturo; Pow-Sang, Julio M; Budzevich, Mikalai M; Basanta, David; Lynch, Conor C

    2016-01-01

    The ability to rapidly assess the efficacy of therapeutic strategies for incurable bone metastatic prostate cancer is an urgent need. Pre-clinical in vivo models are limited in their ability to define the temporal effects of therapies on simultaneous multicellular interactions in the cancer-bone microenvironment. Integrating biological and computational modeling approaches can overcome this limitation. Here, we generated a biologically driven discrete hybrid cellular automaton (HCA) model of bone metastatic prostate cancer to identify the optimal therapeutic window for putative targeted therapies. As proof of principle, we focused on TGFβ because of its known pleiotropic cellular effects. HCA simulations predict an optimal effect for TGFβ inhibition in a pre-metastatic setting with quantitative outputs indicating a significant impact on prostate cancer cell viability, osteoclast formation and osteoblast differentiation. In silico predictions were validated in vivo with models of bone metastatic prostate cancer (PAIII and C4-2B). Analysis of human bone metastatic prostate cancer specimens reveals heterogeneous cancer cell use of TGFβ. Patient specific information was seeded into the HCA model to predict the effect of TGFβ inhibitor treatment on disease evolution. Collectively, we demonstrate how an integrated computational/biological approach can rapidly optimize the efficacy of potential targeted therapies on bone metastatic prostate cancer. PMID:27411810

  17. Real Time Metastatic Route Tracking of Orthotopic PC-3-GFP Human Prostate Cancer Using Intravital Imaging.

    Science.gov (United States)

    Zhang, Yong; Wang, Xiaoen; Hoffman, Robert M; Seki, Naohiko

    2016-04-01

    The cellular basis of metastasis is poorly understood. An important step to understanding this process is to be able to visualize the routes by which cancer cells migrate from the primary tumor to various distant sites to eventually form metastasis. Our laboratory previously developed single-cell in vivo imaging using fluorescent proteins to label cancer cells. In the present study, using PC-3 human prostate cancer cells labeled with green fluorescent protein (GFP) and orthotopic tumor transplantation, we have imaged in live mice various highly diverse routes by which PC-3 cells metastasize superiorly and inferiorly to distant sites, including in the portal area, stomach area, and urogenital system. Imaging began at day 9, at which time distant metastasis had already occurred, and increased at each imaging point at days 10, 13, 14, and 16. Metastatic cells were observed migrating superiorly and inferiorly from the primary tumor as well as in lymphatic channels and trafficking in various organ systems demonstrating that PC-3 has multiple metastatic routes similar to hormone-independent advanced-stage prostate cancer in the clinic. PMID:26515240

  18. NKX3.1 as a Marker of Prostatic Origin in Metastatic Tumors

    OpenAIRE

    Gurel, Bora; Ali, Tehmina Z.; Montgomery, Elizabeth A.; Begum, Shahnaz; Hicks, Jessica; Goggins, Michael; Eberhart, Charles G.; Clark, Douglas P.; Bieberich, Charles J.; Epstein, Jonathan I.; Marzo, Angelo M. De

    2010-01-01

    NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Although most studies have shown that staining for NKX3.1 protein is positive in the majority of primary prostatic adenocarcinomas, it has been shown to be downregulated in many high-grade prostate cancers, and completely lost in the majority of metastatic prostate cancers (eg, in 65% to 78% of lesions). A recent study showed that NKX3.1 staining with a novel antibody was highly sensitive and specific for high-grade prostat...

  19. Effects of Marine Phospholipids Extract on the Lipid Levels of Metastatic and Nonmetastatic Prostate Cancer Patients

    OpenAIRE

    Küllenberg de Gaudry, Daniela; Taylor, Lenka A.; Kluth, Jessica; Hübschle, Tobias; Fritzsche, Jonas; Hildenbrand, Bernd; Pletschen, Lars; Schilli, Karin; Hodina, Arwen; Griffith, Lee S.; Breul, Jürgen; Unger, Clemens; Massing, Ulrich

    2014-01-01

    High intake of omega-3 fatty acids (n-3 FAs) from fish has shown to reduce metastatic progression of prostate cancer. This clinical trial investigated the influence of high n-3 FA intake (marine phospholipids, MPL) on the FA composition of blood lipids, lysophosphatidylcholine (LPC), and on lipoproteins in prostate cancer patients and elderly men without prostate cancer. MPL supplementation resulted in a significant increase of n-3 FAs (eicosapentaenoic and docosahexaenoic acid) in blood lipi...

  20. 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.

  1. 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.

  2. [Treatment of metastatic castration-resistant prostate cancer].

    Science.gov (United States)

    Caffo, Orazio

    2015-01-01

    The treatment of metastatic castration-resistant prostate cancer (mCRPC) represents one of the oncological fields where the most impressive improvements has been observed in the last decades. At the beginning of this century, the expected survival of mCRPC patients was not more than 12 months. After the introduction of docetaxel in the clinical practice in 2004, and the recent availability of new drugs cabazitaxel, abiraterone acetate, enzalutamide, and radium-223 the landscape is dramatically changed with an expected median survival of about three years. The possibility of administering docetaxel, abiraterone acetate, and enzalutamide as first line treatment, and cabazitaxel, abiretone acetate, and enzalutamide as second line, as well as the availability of radium-223 for the treatment of mCRPC patients regardless of chemotherapy administration, changed the natural history of the disease. At the same time, it is probable that also the biology of the disease is changing with the appearance of mechanisms of resistance which are common to all the drugs. This plays a central role in sequencing the available drugs not only in the first and second line setting but also beyond the second line. The future challenges for the oncologists will be to develop new drugs able to overcome the resistances, mainly when they are native, to find the optimal sequence to optimize the use of available drugs, to place at the best place other active drugs, such as vaccines and radiopharmaceuticals, to exploit the new drugs also in a hormone-sensitive phase. PMID:25621779

  3. 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.

  4. Docetaxel-related toxicity in metastatic hormone-sensitive and metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Schweizer, Michael T; Gulati, Roman; Mostaghel, Elahe A; Nelson, Peter S; Montgomery, R Bruce; Yu, Evan Y; Cheng, Heather H

    2016-07-01

    Docetaxel plus androgen deprivation therapy (ADT) offers a survival benefit in metastatic hormone-sensitive prostate cancer (mHSPC). However, one trial evaluating docetaxel in mHSPC (GETUG-AFU15) showed unexpected toxicity; raising concerns that docetaxel may carry increased toxicity when used to treat mHSPC compared to metastatic castration-resistant prostate cancer (mCRPC). We conducted a retrospective analysis evaluating differences in toxicity based on the clinical state (i.e., mHSPC vs. mCRPC) that docetaxel was used. Patients initiating docetaxel between 1/1/2014 and 7/15/2015 were included, with the former date chosen to coincide with the press release for the first mHSPC study that showed a survival benefit with early docetaxel; ensuring contemporary docetaxel-treated cohorts. Thirty-nine mCRPC and 22 mHSPC patients were included. Compared to mCRPC, mHSPC patients were younger (median years: 66.3 vs. 71.8, P = 0.007); had better performance status (ECOG 0-1: 100 vs. 62 %, P < 0.0001); and used opiates less frequently (29 vs. 66 %, P = 0.04). Neutropenic fevers occurred in 9 and 5 % (P = 0.95) of men with mHSPC and mCRPC, respectively. Other toxicities also occurred at similar rates between cohorts. The incidence of any toxic event was 73 and 67 % (P = 0.84) for men with mHSPC and mCRPC, respectively. Within the mHSPC cohort, neutropenic fevers occurred at a similar rate regardless of the time interval between initiating ADT and the start of docetaxel. We did not observe a significant difference in toxicity between mHSPC and mCRPC patients receiving docetaxel. However, the small sample size and retrospective nature of this study limit our ability to draw definitive conclusions. PMID:27300548

  5. 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.

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

    International Nuclear Information System (INIS)

    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

  7. 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

    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...... 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....

  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. Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: Results from the STAMPEDE and CHAARTED trials

    NARCIS (Netherlands)

    R.J. van Soest (Robert Jan); R. de Wit (Ronald)

    2015-01-01

    textabstractAndrogen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), fol

  10. 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.

  11. Adenosine deaminase complexing protein (ADCP) expression and metastatic potential in prostatic adenocarcinomas.

    Science.gov (United States)

    Dinjens, W N; Ten Kate, J; Kirch, J A; Tanke, H J; Van der Linden, E P; Van den Ingh, H F; Van Steenbrugge, G J; Meera Khan, P; Bosman, F T

    1990-03-01

    The expression of the adenosine deaminase complexing protein (ADCP) was investigated by immunohistochemistry in the normal and hyperplastic human prostate, in 30 prostatic adenocarcinomas, and in seven human prostatic adenocarcinoma cell lines grown as xenografts in athymic nude mice. In the normal and hyperplastic prostate, ADCP was localized exclusively in the apical membrane and the apical cytoplasm of the glandular epithelial cells. In prostatic adenocarcinomas, four distinct ADCP expression patterns were observed: diffuse cytoplasmic, membranous, both cytoplasmic and membranous, and no ADCP expression. The expression patterns were compared with the presence of metastases. We found an inverse correlation between membranous ADCP immunoreactivity and metastatic propensity. Exclusively membranous ADCP immunoreactivity occurred only in non-metastatic tumours. In contrast, the metastatic tumours showed no or diffuse cytoplasmic ADCP immunoreactivity. This suggests that immunohistochemical detection of ADCP might predict the biological behaviour of prostatic cancer. However, the occurrence of membranous ADCP immunoreactivity in the xenograft of a cell line (PC-EW), derived from a prostatic carcinoma metastasis, indicates that not only the tendency to metastasize modulates ADCP expression. PMID:1692338

  12. 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.

  13. Nomogram for overall survival of Japanese patients with bone-metastatic prostate cancer

    OpenAIRE

    Miyoshi, Yasuhide; Noguchi, Kazumi; Yanagisawa, Masahiro; Taguri, Masataka; Morita, Satoshi; Ikeda, Ichiro; Fujinami, Kiyoshi; Miura, Takeshi; Kobayashi, Kazuki; Uemura, Hiroji

    2015-01-01

    Background We analyzed the relationship between prostate cancer outcomes and pretreatment clinical factors and developed a prognostic nomogram of overall survival (OS) of patients with bone metastasis. Methods From 1993 to 2011, 463 consecutive patients were treated for bone-metastatic prostate cancer. Data sets from 361 patients were used to develop a nomogram (training data), and data sets of 102 patients were used for validation of the nomogram (validation data). Using the external validat...

  14. Complementary traditional Chinese medicine therapy improves survival in patients with metastatic prostate cancer

    Science.gov (United States)

    Liu, Jui-Ming; Lin, Po-Hung; Hsu, Ren-Jun; Chang, Ying-Hsu; Cheng, Kuan-Chen; Pang, See-Tong; Lin, Shun-Ku

    2016-01-01

    Abstract More than 50% of prostate cancer patients have used traditional Chinese medicine (TCM) in Taiwan. However, the long-term clinical efficacy of TCM in prostate cancer patients remains unclear. Here, we investigated the relationship between TCM use and the survival of prostate cancer patients. A retrospective nationwide cohort study of prostate cancer patients was conducted between 1998 and 2003 using the Taiwan National Health Insurance Research Database. Patients were classified as TCM users or nonusers, and monitored from the day of prostate cancer diagnosis to death or end of 2012. The association between death risk and TCM use was determined using Cox proportional-hazards models and Kaplan–Meier curves. Of the 1132 selected prostate cancer patients, 730 (64.5%) and 402 (35.5%) were TCM users and nonusers, respectively. The mean follow-up period was 8.38 years, and 292 (25.8%) deaths were reported. TCM users had a decreased mortality rate (21.9%) compared with nonusers (32.8%). A lower death risk was observed with longer TCM use, especially in patients who used TCM for ≧200 days (adjusted hazard ratio [aHR] 0.61, 95% confidence interval [CI] 0.44–0.84). TCM users with metastatic prostate cancer had a significant lower HR than nonusers (aHR 0.70, 95% CI 0.51–0.95). Chai-Hu-Jia-Long-Gu-Mu-Li-Tang was the most significant TCM formulae for improving survival in metastatic prostate cancer (aHR 0.18, 95% CI 0.04–0.94). The result suggested that complementary TCM therapy might be associated with a reduced risk of death in metastatic prostate cancer patients. PMID:27495088

  15. 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.

  16. 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.

  17. 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

  18. Current status of primary pharmacotherapy and future perspectives toward upfront therapy for metastatic hormone-sensitive prostate cancer.

    Science.gov (United States)

    Shiota, Masaki; Eto, Masatoshi

    2016-05-01

    Since 1941, androgen deprivation therapy has been the primary treatment for metastatic hormone-sensitive prostate cancer. Androgen deprivation therapy consists of several regimens that vary according to therapeutic modality, as well as treatment schedule. Androgen deprivation therapy initially shows excellent antitumor effects, such as relief of cancer-related symptoms, tumor marker decline and tumor shrinking. However, most metastatic hormone-sensitive prostate cancer cases eventually develop castration resistance and become lethal. Taxanes, such as docetaxel and cabazitaxel, as well as novel androgen receptor-targeting agents, such as abiraterone acetate and enzalutamide, have emerged for metastatic castration-resistant prostate cancer. The concept and principle of primary therapy for metastatic hormone-sensitive prostate cancer has remained unchanged for decades. Recently, upfront docetaxel chemotherapy has been shown to prolong overall survival in men with metastatic hormone-sensitive prostate cancer, and would lead to a paradigm shift in primary pharmacotherapy for metastatic hormone-sensitive prostate cancer. This raises the possibility of upfront use of taxanes, as well as novel androgen receptor-targeting agents combined with androgen deprivation therapy. The present review summarizes the current status of primary pharmacotherapy for metastatic hormone-sensitive prostate cancer, and discusses future perspectives in this field. PMID:27062039

  19. 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...

  20. 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 fina...

  1. 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

  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. Metastatic superscan in prostate carcinoma on gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography scan

    Science.gov (United States)

    Agarwal, Krishan Kant; Tripathi, Madhavi; Kumar, Rajeev; Bal, Chandrasekhar

    2016-01-01

    We describe the imaging features of a metastatic superscan on gallium-68 Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)], abbreviated as gallium-68-prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging. 68Ga-PSMA is novel radiotracer undergoing evaluation for PET/CT imaging of prostate carcinoma. This patient had a superscan of metastases on conventional bone scintigraphy and was referred for 68Ga-PSMA PET/CT to evaluate the feasibility of 177Lu-PSMA therapy. PMID:27095868

  4. 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.

  5. 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.

  6. 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.

  7. Redefining Hormone Sensitive Disease in Advanced Prostate Cancer

    OpenAIRE

    Xiaoyu Hou; Flaig, Thomas W.

    2012-01-01

    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 pros...

  8. Cancer of the prostate presenting with diffuse osteolytic metastatic bone lesions: a case report

    Directory of Open Access Journals (Sweden)

    Segamwenge Innocent Lule

    2012-12-01

    Full Text Available Abstract Introduction Prostate cancer is the second most common cancer in men and the fifth most common cancer worldwide. In the USA it is more common in African-American men than in Caucasian men. Prostate cancer frequently metastasizes to bone and the lesions appear osteoblastic on radiographs. Presentation with diffuse osteolytic bone lesions is rare. We describe an unusual presentation of metastatic prostate cancer with diffuse osteolytic bone lesions. Case presentation A 65-year-old Namibian man presented with anemia, thrombocytopenia and worsening back pains. In addition he had complaints of effort intolerance, palpitations, dysuria and mild symptoms of bladder outlet obstruction. On examination he was found to be anemic, had a swollen tender right shoulder joint and spine tenderness to percussion. On digital rectal examination he had asymmetrical enlargement of the prostate which felt nodular and hard with diffuse firmness in some parts. His prostate-specific antigen was greater than 100ng/mL and he had diffuse osteolytic lesions involving the right humerus, and all vertebral, femur and pelvic bones. His screen for multiple myeloma was negative and the prostate biopsy confirmed prostate cancer. Conclusion Prostate cancer rarely presents with diffuse osteolytic bone lesions and should be considered in the differential diagnosis when evaluating male patients with osteolytic bone lesions.

  9. 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.

  10. 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.

  11. Irrefutable evidence for the use of docetaxel in newly diagnosed metastatic prostate cancer: results from the STAMPEDE and CHAARTED trials

    OpenAIRE

    Soest, Robert Jan; de Wit, Ronald

    2015-01-01

    textabstractAndrogen deprivation therapy (ADT) has been used in the treatment of metastatic prostate cancer since the first description of its hormonal dependence in 1941. In 2004, docetaxel chemotherapy became the mainstay of treatment in metastatic castration-resistant prostate cancer (mCRPC), following robust, albeit modest, survival benefit in two randomized phase 3 trials. The recently published CHAARTED trial was the first to show that combining ADT with docetaxel in men with hormone-na...

  12. 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.

  13. Immunotherapy and Immune Evasion in Prostate Cancer

    OpenAIRE

    Archana Thakur; Ulka Vaishampayan; Lum, Lawrence G.

    2013-01-01

    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 o...

  14. 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

  15. 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...

  16. Activation of the hedgehog pathway in advanced prostate cancer

    OpenAIRE

    McCormick Frank; Chen Kai; He Nonggao; Chi Sumin; Zhang Xiaoli; Li Chengxin; Sheng Tao; Gatalica Zoran; Xie Jingwu

    2004-01-01

    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 ...

  17. Identification of genes regulating migration and invasion using a new model of metastatic prostate cancer

    International Nuclear Information System (INIS)

    Understanding the complex, multistep process of metastasis remains a major challenge in cancer research. Metastasis models can reveal insights in tumor development and progression and provide tools to test new intervention strategies. To develop a new cancer metastasis model, we used DU145 human prostate cancer cells and performed repeated rounds of orthotopic prostate injection and selection of subsequent lymph node metastases. Tumor growth, metastasis, cell migration and invasion were analyzed. Microarray analysis was used to identify cell migration- and cancer-related genes correlating with metastasis. Selected genes were silenced using siRNA, and their roles in cell migration and invasion were determined in transwell migration and Matrigel invasion assays. Our in vivo cycling strategy created cell lines with dramatically increased tumorigenesis and increased ability to colonize lymph nodes (DU145LN1-LN4). Prostate tumor xenografts displayed increased vascularization, enlarged podoplanin-positive lymphatic vessels and invasive margins. Microarray analysis revealed gene expression profiles that correlated with metastatic potential. Using gene network analysis we selected 3 significantly upregulated cell movement and cancer related genes for further analysis: EPCAM (epithelial cell adhesion molecule), ITGB4 (integrin β4) and PLAU (urokinase-type plasminogen activator (uPA)). These genes all showed increased protein expression in the more metastatic DU145-LN4 cells compared to the parental DU145. SiRNA knockdown of EpCAM, integrin-β4 or uPA all significantly reduced cell migration in DU145-LN4 cells. In contrast, only uPA siRNA inhibited cell invasion into Matrigel. This role of uPA in cell invasion was confirmed using the uPA inhibitors, amiloride and UK122. Our approach has identified genes required for the migration and invasion of metastatic tumor cells, and we propose that our new in vivo model system will be a powerful tool to interrogate the metastatic

  18. How I do it: Prescribing abiraterone acetate for metastatic castration resistant prostate cancer.

    Science.gov (United States)

    Wang, Yuding; Dason, Shawn; Shayegan, Bobby

    2016-08-01

    Abiraterone acetate (AA) is a selective irreversible inhibitor of CYP 17, a key enzyme in androgen biosynthesis. The efficacy and safety of AA in improving survival and quality of life in metastatic castration resistant prostate cancer (mCRPC) has been demonstrated in two landmark clinical trials (COU-AA-301 and COU-AA-302). This article will review the rationale, pharmacology, clinical indications and contraindications, administration, and adverse effects of AA administration in mCRPC. PMID:27544566

  19. Predicting Response to Hormonal Therapy and Survival in Men with Hormone Sensitive Metastatic Prostate Cancer

    OpenAIRE

    Grivas, Petros D; Robins, Diane M.; Hussain, Maha

    2012-01-01

    Androgen deprivation is the cornerstone of the management of metastatic prostate cancer. Despite several decades of clinical experience with this therapy there are no standard predictive biomarkers for response. Although several candidate genetic, hormonal, inflammatory, biochemical, metabolic biomarkers have been suggested as potential predictors of response and outcome, none has been prospectively validated nor has proven clinical utility to date. There is significant heterogeneity in the d...

  20. Effects of occupational therapy on quality of life of patients with metastatic prostate cancer

    OpenAIRE

    Huri, Meral; Huri, Emre; Kayihan, Hulya; Altuntas, Onur

    2015-01-01

    Objectives: To evaluate the efficiency of occupational therapy relative to a home program in improving quality of life (QoL) among men who were treated for metastatic prostate cancer (MPC). Methods: Fifty-five men were assigned randomly to either the 12-week cognitive behavioral therapy based occupational therapy (OT-CBSM) intervention (treatment group) or a home program (control group) between March 2012 and August 2014 in the Department of Occupational Therapy, Faculty of Health Sciences, H...

  1. The evolving role of cytotoxic chemotherapy in the management of patients with metastatic prostate cancer.

    Science.gov (United States)

    Diamond, Elan; Garcias, María del Carmen; Karir, Beerinder; Tagawa, Scott T

    2015-02-01

    Prostate cancer (PC) is the most common cancer in men in the United States. Although outcomes are excellent for early-stage disease, survival for men with metastatic PC is limited. While older studies did not supported the use of chemotherapy in PC, the efficacy of taxane chemotherapy plus prednisone is now well established in men with metastatic castration resistant PC (CRPC). The results of CHAARTED trial have further expanded the use of chemotherapy to patients with metastatic hormone-sensitive disease. The clinical efficacy of taxanes over other chemotherapeutics may be a result of its ability to inhibit microtubule-dependent trafficking of proteins such as the androgen-receptor (AR). Ongoing research uses chemotherapy earlier in the disease course as well as explores the utility of combining cytotoxic chemotherapy with biologic agents. PMID:25762124

  2. Metastatic prostate cancer with elevated serum levels of CEA and CA19-9

    Directory of Open Access Journals (Sweden)

    Guang-Dar Juang

    2014-03-01

    Full Text Available Prostate-specific antigen (PSA is well known as a specific tumor marker for prostate cancer, but carcinoembryonic antigen (CEA- and carbohydrate antigen 19-9 (CA19-9-elevating adenocarcinomas originating in the prostate gland are rare. We report a case of metastatic adenocarcinoma of the prostate gland with a high serum level of CEA and CA19-9 in a 78-year-old man in whom prostate cancer (T3N1M1 had been diagnosed 2 years ago and who was treated with androgen deprivation therapy. He visited the emergency department because of a loss of appetite and abdominal pain. The serum CEA and CA19-9 levels were increased to 218.9 ng/mL (normal, <5 ng/mL and 212 ng/mL (normal, <27 ng/mL, respectively. The serum PSA level was slightly elevated (4.41 ng/mL. Computed tomography demonstrated multiple liver metastases, para-aortic lymph node enlargement, and lung metastases. A liver biopsy was performed and the specimen showed high-grade adenocarcinoma with focal positive staining for PSA. Despite chemotherapy with docetaxel, the patient died 3 months after treatment. Based on this case and a review of the literature, an aggressive variant of prostatic carcinoma with a high serum level of CEA and CA19-9 and a low PSA level was shown to progress rapidly with a poor prognosis.

  3. Atrophy of the Tongue as the Presenting Feature of Metastatic Prostate Cancer

    OpenAIRE

    Abdullah, Zreik; Darrad, Maitrey; Pathak, Sanjeev

    2011-01-01

    Prostate cancer is the most frequently diagnosed solid organ cancer in men and is the second leading cause of cancer-related deaths in men in the United Kingdom. Commonly, it metastasizes to bones and lymph nodes, however, in advanced hormonerefractory disease it may involve the skull base leading to associated cranial nerve palsies. Cranial nerve palsy as the presenting feature of advanced hormone-sensitive prostate cancer is extremely rare. To the best of our knowledge, we report the first ...

  4. 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]...

  5. Enhanced detection of metastatic prostate cancer cells in human plasma with lipid bodies staining

    International Nuclear Information System (INIS)

    Reprogramming of energy metabolism of malignant cancer cells confers competitive advantage in growth environments with limited resources. However, not every process of cancer development is associated with competition for resources. During hematogenous transport, cancer cells are exposed to high levels of oxygen and nutrients. Does energy metabolism of cancer cells change as a function of exposure to the bloodstream? Could such changes be exploited to improve the detection of circulating tumor cells (CTC)? These questions have clinical significance, but have not yet been sufficiently examined. The energy metabolism was examined as a function of incubation in nutrient-rich plasma in prostate metastatic cancer cells LNCaP and non-transformed prostate epithelial cells RWPE1. Uptake kinetics of a fluorescent glucose analog (2-NBD) and lipophilic dyes (DiD & Bodipy) were measured in both cell lines, as well as in peripheral blood mononuclear cells (PBMC). LNCaP cells exhibited hyper-acetylation of low molecular weight proteins compared to RWPE1 cells. Following plasma incubation, protein lysine acetylation profile was unchanged for LNCaP cells while significantly altered for RWPE1 cells. O-linked glycosylated protein profiles were different between LNCaP and RWPE1 cells and varied in both cell lines with plasma incubation. Maximal respiration or glycolytic capacities was unchanged in LNCaP cells and impaired in RWPE1 cells following plasma incubation. However, the uptake rates of 2-NBD and DiD were insufficient for discrimination of LNCaP, or RWPE1 cells from PBMC. On the other hand, both RWPE1 and LNCaP cells exhibited intracellular lipid bodies following plasma incubation; whereas, PBMC did not. The presence of lipid bodies in LNCaP cells permitted retention of Bodipy dye and allowed discrimination of LNCaP cells from PBMC with flow cytometry. Despite clear differences in energy metabolism, metastatic prostate cancer cells could not be efficiently distinguished from

  6. 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.

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

    OpenAIRE

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

    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 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 a...

  8. Human antibodies targeting cell surface antigens overexpressed by the hormone refractory metastatic prostate cancer cells: ICAM-1 is a tumor antigen that mediates prostate cancer cell invasion

    OpenAIRE

    Conrad, Fraser; Zhu, Xiaodong; Zhang, Xin; Chalkley, Robert J.; Burlingame, Alma L; Marks, James D.; Liu, Bin

    2009-01-01

    Transition from hormone-sensitive to hormone-refractory metastatic tumor types poses a major challenge for prostate cancer treatment. Tumor antigens that are differentially expressed during this transition are likely to play important roles in imparting prostate cancer cells with the ability to grow in a hormone-deprived environment and to metastasize to distal sites such as the bone and thus, are likely targets for therapeutic intervention. To identify those molecules and particularly cell s...

  9. 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 m......CRPC with a good response to first-line docetaxel [serum prostate specific antigen (PSA) decrease ≥50%; no clinical/radiological progression]. We analysed the impact of management at relapse (docetaxel rechallenge or non-taxane-based therapy) on PSA response, symptomatic response (performance status....../pain/analgesic consumption), and overall survival (OS). We used multivariate stepwise logistic regression to analyse potential predictors of a favourable outcome. RESULTS: We identified 270 good responders to first-line docetaxel. The median progression-free interval (PFI) was 6 months from the last docetaxel dose...

  10. 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.

  11. Immunotherapy and Immune Evasion in Prostate Cancer

    International Nuclear Information System (INIS)

    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

  12. 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.

  13. 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

  14. 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.

  15. A Phase 2 Study of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer Who Had Received Docetaxel-based Chemotherapy

    OpenAIRE

    SATOH, TAKEFUMI; Uemura, Hiroji; Tanabe, Kazunari; Nishiyama, Tsutomu; Terai, Akito; Yokomizo, Akira; Nakatani, Tatsuya; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxel-based chemotherapy. Methods Men (aged ≥20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: ≥5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with ≥1 regimen being ...

  16. 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.

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

    International Nuclear Information System (INIS)

    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.

  18. 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. PMID:26721408

  19. Cytotoxic chemotherapy in the contemporary management of metastatic castration-resistant prostate cancer (mCRPC).

    Science.gov (United States)

    Sonpavde, Guru; Wang, Christopher G; Galsky, Matthew D; Oh, William K; Armstrong, Andrew J

    2015-07-01

    For several years, docetaxel was the only treatment shown to improve survival of patients with metastatic castration-resistant prostate cancer (mCRPC). There are now several novel agents available, although chemotherapy with docetaxel and cabazitaxel continues to play an important role. However, the increasing number of available agents will inevitably affect the timing of chemotherapy and therefore it may be important to offer this approach before declining performance status renders patients ineligible for chemotherapy. Patient selection is also important to optimise treatment benefit. The role of predictive biomarkers has assumed greater importance due to the development of multiple agents and resistance to available agents. In addition, the optimal sequence of treatments remains undefined and requires further study in order to maximize long-term outcomes. We provide an overview of the clinical data supporting the role of chemotherapy in the treatment of mCRPC and the emerging role in metastatic castration-sensitive prostate cancer. We review the key issues in the management of patients including selection of patients for chemotherapy, when to start chemotherapy, and how best to sequence treatments to maximise outcomes. In addition, we briefly summarise the promising new chemotherapeutic agents in development in the context of emerging therapies. PMID:25046451

  20. 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.

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Glycogen synthase kinase-3β inhibition depletes the population of prostate cancer stem/progenitor-like cells and attenuates metastatic growth

    Science.gov (United States)

    Kroon, Jan; in 't Veld, Lars S.; Buijs, Jeroen T.; Cheung, Henry; van der Horst, Geertje; van der Pluijm, Gabri

    2014-01-01

    Cancer cells with stem or progenitor properties play a pivotal role in the initiation, recurrence and metastatic potential of solid tumors, including those of the human prostate. Cancer stem cells are generally more resistant to conventional therapies thus requiring the characterization of key pathways involved in the formation and/or maintenance of this malignant cellular subpopulation. To this end, we identified Glycogen Synthase Kinase-3β (GSK-3β) as a crucial kinase for the maintenance of prostate cancer stem/progenitor-like cells and pharmacologic inhibition of GSK-3β dramatically decreased the size of this cellular subpopulation. This was paralleled by impaired clonogenicity, decreased migratory potential and dramatic morphological changes. In line with our in vitro observations, treatment with a GSK-3β inhibitor leads to a complete loss of tumorigenicity and a decrease in metastatic potential in preclinical in vivo models. These observed anti-tumor effects appear to be largely Wnt-independent as simultaneous Wnt inhibition does not reverse the observed antitumor effects of GSK-3β blockage. We found that GSK-3β activity is linked to cytoskeletal protein F-actin and inhibition of GSK-3β leads to disturbance of F-actin polymerization. This may underlie the dramatic effects of GSK-3β inhibition on prostate cancer migration. Furthermore, GSK-3β inhibition led to strongly decreased expression of several integrin types including the cancer stem cell-associated α2β1 integrin. Taken together, our mechanistic observations highlight the importance of GSK-3β activity in prostate cancer stemness and may facilitate the development of novel therapy for advanced prostate cancer. PMID:25344861

  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. 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...... change were registered during treatment with CA and previous/subsequent novel androgen receptor targeting therapies. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. A median of 6 versus 5 treatment cycles was administered in patients treated...

  8. 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.

  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. 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...

  11. 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

  12. 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

  13. Clamp ablation of the testes compared to bilateral orchiectomy as androgen deprivation therapy for advanced prostate cancer

    OpenAIRE

    AD Zarrabi; CF Heyns

    2011-01-01

    PURPOSE: Burdizzo clamp ablation of the testes (CAT) may provide an incisionless, cost-effective form of androgen deprivation therapy (ADT) in men with adenocarcinoma of the prostate (ACP) who find bilateral orchiectomy (BO) unacceptable or can not afford medical ADT. The aim of this study was to compare CAT with BO as primary ADT in men with ACP. MATERIALS AND METHODS: Written, informed consent was obtained from men with locally advanced or metastatic ACP. Patients were prospectively randomi...

  14. 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.

  15. 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. PMID:24750803

  16. 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

  17. Predictors of overall survival in patients with metastatic castration-resistant prostate cancer

    Directory of Open Access Journals (Sweden)

    A. S. Markova

    2015-01-01

    Full Text Available Objective: to estimate overall survival (OS rates in patients with metastatic castration-resistant prostate cancer (mCRPC, who have received currently available drugs and to identify the predictors of OS.Subjects and methods. The case histories of 112 patients with mCRPC treated at the N.N. Blokhin Russian Cancer Research Center in 2005 to 2014 were retrospectively analyzed. All the patients had received standard regimens based on docetaxel, cabazitaxel, abiraterone acetate in combination with prednisolone.Results. Whatever the treatment option was, three-year OS rate was 32.0 ± 5.44 %; median survival was 24.3 months. The following poor prognostic factors for OS were pain syndrome; an ECOG performance status score of 2; the levels of prostate-specific antigen ≥ 288 ng/ml, lactate dehydrogenase ≥ 450 U/l, alkaline phosphatase ≥ 250 U/l, calcium < 2.28 mmol/l, and hemoglobin < 11.5 g/dl; as well as < 24 months’ duration of a response to hormonal therapy.Conclusion. The use of standard drug treatment regimen for mCRPC may increase survival in this category of patients to achieve 3-years OV; and the identified factors of OV may aid in choosing treatment policy.

  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. 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.

  20. 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...... in secondary endpoints were observed. CONCLUSIONS: ERG expression was not associated with risk of CRPC suggesting that ERG is not a candidate biomarker for predicting response to primary ADT in patients diagnosed with advanced and/or metastatic PCa....

  1. 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....

  2. Galeterone for the treatment of advanced prostate cancer: the evidence to date

    Directory of Open Access Journals (Sweden)

    Bastos DA

    2016-07-01

    Full Text Available Diogo A Bastos,1 Emmanuel S Antonarakis2 1Department of Oncology, Hospital Sirio-Libanes, Sao Paulo, Brazil; 2Department of Oncology and Urology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA Abstract: Major advances have been achieved recently in the treatment of metastatic castration-resistant prostate cancer, resulting in significant improvements in quality of life and survival with the use of several new agents, including the next-generation androgen receptor (AR-targeted drugs abiraterone and enzalutamide. However, virtually all patients will eventually progress on these therapies and most will ultimately die of treatment-refractory metastatic disease. Recently, several mechanisms of resistance to AR-directed therapies have been uncovered, including the AR splice variant 7 (AR-V7, which is a ligand-independent constitutionally-active form of the AR that has been associated with poor outcomes to abiraterone and enzalutamide. Galeterone, a potent anti-androgen with three modes of action (CYP17 lyase inhibition, AR antagonism, and AR degradation, is a novel agent under clinical development that could potentially target both full-length AR and aberrant AR, including AR-V7. In this manuscript, we will first discuss the biological mechanisms of action of galeterone and then review the safety and efficacy data from Phase I and II clinical studies of galeterone in patients with metastatic castration-resistant prostate cancer. A Phase III study of galeterone (compared against enzalutamide in AR-V7-positive patients is currently underway, and represents the first pivotal trial using a biomarker-selection design in this disease. Keywords: galeterone, AR splice variants, AR-V7, castration-resistant prostate cancer

  3. Genomic alterations indicate tumor origin and varied metastatic potential of disseminated cells from prostate-cancer patients

    OpenAIRE

    Holcomb, Ilona N.; Grove, Douglas I.; Kinnunen, Martin; Friedman, Cynthia L.; Gallaher, Ian S.; Todd M. Morgan; Sather, Cassandra L.; Delrow, Jeffrey J; Peter S Nelson; Lange, Paul H.; Ellis, William J; True, Lawrence D.; Janet M Young; Hsu, Li; Trask, Barbara J.

    2008-01-01

    Disseminated epithelial cells can be isolated from the bone marrow of a far greater fraction of prostate-cancer patients than the fraction of patients who progress to metastatic disease. To provide a better understanding of these cells, we have characterized their genomic alterations. We first present an array comparative genomic hybridization method capable of detecting genomic changes in the small number of disseminated cells (10-20) that can typically be obtained from bone-marrow aspirates...

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

    OpenAIRE

    Huerta, Angel Segura; Santos, Encarnación Reche; Campos, Gema Bruixola; Coloma, Carmen Salvador; Gómez, Oscar Niño

    2013-01-01

    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 performa...

  5. Role of chemotherapy in combination with hormonal therapy in first-line treatment of metastatic hormone-sensitive prostate cancer.

    Science.gov (United States)

    Ceresoli, G L; De Vincenzo, F; Sauta, M G; Bonomi, M; Zucali, P A

    2015-12-01

    Prostate cancer (PC) is a heterogeneous disease, whose growth is driven by androgens and androgen receptors. Androgen deprivation therapy (ADT) is the standard treatment of hormone-naïve metastatic disease. The majority of patients are treated with medical castration with GnRH agonists or antagonists, which usually determines a profound PSA decline and a radiological and clinical benefit. However, essentially all patients experience progression to castration-resistant prostate cancer (CRPC), and overall prognosis remains disappointing. Early targeting of cells that survive hormonal therapy may potentially prevent the development of CRPC. Several trials have explored the use of combination therapy with ADT and chemotherapy, targeting both the androgen dependent and independent cells simultaneously. Docetaxel was administered in combination with ADT to men with hormone-naïve metastatic prostate cancer, in the attempt to improve the duration and quality of patient survival. Three large randomized trials (the GETUG-15, CHAARTED and more recently the STAMPEDE study) have assessed these endpoints, with partially conflicting results. Overall, the results from these trials seem to support the use of early docetaxel combined with ADT in selected hormone-naïve metastatic PC patients. Full publication of the results of all studies, with longer follow-up, and the results of other ongoing trials in this setting will hopefully further define the role and the indications of this therapeutic strategy. PMID:26222275

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

    OpenAIRE

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

    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...

  7. 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

  8. A Phase 2 Trial of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer and without Prior Chemotherapy (JPN-201 Study)

    OpenAIRE

    Matsubara, Nobuaki; Uemura, Hirotsugu; SATOH, TAKEFUMI; Suzuki, Hiroyoshi; Nishiyama, Tsutomu; Uemura, Hiroji; Hashine, Katsuyoshi; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated. Methods Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicent...

  9. 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

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

    OpenAIRE

    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 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 ...

  11. Efficacy of Sm-153 radionuclide therapy for bone pain palliation in metastatic prostate cancer

    International Nuclear Information System (INIS)

    period. Conclusion: in our study we conclude that, Sm153 was found feasible, effective and safe radionuclide therapy for bone pain palliation and reduced the overall-long term cost of pain palliation while improving the quality of life in patients with metastatic prostate cancer. (authors)

  12. [Metastatic castration-resistant prostate cancer : Clinical data, new treatment options and therapy monitoring].

    Science.gov (United States)

    Miller, K; Albers, P; Eichenauer, R; Geiges, G; Grimm, M-O; König, F; Mickisch, G; Pfister, D; Schwentner, C; Suttmann, H; Zastrow, S

    2016-09-01

    Therapies currently available in Germany for metastatic castration-resistant prostate cancer (mCRPC) include docetaxel, cabazitaxel, abiraterone acetate, enzalutamide and radium-223, all of which offer a potential survival benefit that adds up in their sequential application to a significant overall survival benefit. However, the optimal sequencing of these agents is still unclear. In the absence of evidence, treatment selection is based on the particular situation and on comorbid conditions of each individual patient. Furthermore, predictive markers to facilitate the selection of patients for a specific therapy or sequence of therapies remain an unmet need. However, with the recently discovered androgen receptor splice variant V7, which mediates (cross)resistance to or between abiraterone and enzalutamide, the first such marker has been identified. It is critical to monitor the response to treatments at prespecified intervals in order to optimize treatment sequencing so that the patient does not miss a valuable therapeutic window to receive alternative treatment that may prolong his life along with good symptom control and preservation of quality of life. PMID:27411995

  13. 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.

  14. Bone-Targeted Therapies in Metastatic Castration-Resistant Prostate Cancer: Evolving Paradigms

    Directory of Open Access Journals (Sweden)

    Joelle El-Amm

    2013-01-01

    Full Text Available Majority of patients with metastatic castrate resistant prostate cancer (mCRPC develop bone metastases which results in significant morbidity and mortality as a result of skeletal-related events (SREs. Several bone-targeted agents are either in clinical use or in development for prevention of SREs. Bisphosphonates were the first class of drugs investigated for prevention of SREs and zoledronic acid is the only bisphosphonate that is FDA-approved for this indication. Another bone-targeted agent is denosumab which is a fully humanized monoclonal antibody that binds to the RANK-L thereby inhibiting RANK-L mediated bone resorption. While several radiopharmaceuticals were approved for pain palliation in mCRPC including strontium and samarium, alpharadin is the first radiopharmaceutical to show significant overall survival benefit. Contemporary therapeutic options including enzalutamide and abiraterone have effects on pain palliation and SREs as well. Other novel bone-targeted agents are currently in development, including the receptor tyrosine kinase inhibitors cabozantinib and dasatinib. Emerging therapeutics in mCRPC has resulted in great strides in preventing one of the most significant sources of complications of bone metastases.

  15. 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. T......' with Zoladex plus flutamide was not clinically superior to orchidectomy in the treatment of patients with advanced prostatic cancer.......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...

  16. 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......, and not based on a critical review of the available evidence, are presented. The various recommendations carried differing degrees of support, as reflected in the wording of the article text and in the detailed voting results recorded in supplementary Material, available at Annals of Oncology online. Detailed...

  17. 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.

  18. Cyclin A1 and P450 Aromatase Promote Metastatic Homing and Growth of Stem-like Prostate Cancer Cells in the Bone Marrow.

    Science.gov (United States)

    Miftakhova, Regina; Hedblom, Andreas; Semenas, Julius; Robinson, Brian; Simoulis, Athanasios; Malm, Johan; Rizvanov, Albert; Heery, David M; Mongan, Nigel P; Maitland, Norman J; Allegrucci, Cinzia; Persson, Jenny L

    2016-04-15

    Bone metastasis is a leading cause of morbidity and mortality in prostate cancer. While cancer stem-like cells have been implicated as a cell of origin for prostate cancer metastasis, the pathways that enable metastatic development at distal sites remain largely unknown. In this study, we illuminate pathways relevant to bone metastasis in this disease. We observed that cyclin A1 (CCNA1) protein expression was relatively higher in prostate cancer metastatic lesions in lymph node, lung, and bone/bone marrow. In both primary and metastatic tissues, cyclin A1 expression was also correlated with aromatase (CYP19A1), a key enzyme that directly regulates the local balance of androgens to estrogens. Cyclin A1 overexpression in the stem-like ALDH(high) subpopulation of PC3M cells, one model of prostate cancer, enabled bone marrow integration and metastatic growth. Further, cells obtained from bone marrow metastatic lesions displayed self-renewal capability in colony-forming assays. In the bone marrow, cyclin A1 and aromatase enhanced local bone marrow-releasing factors, including androgen receptor, estrogen and matrix metalloproteinase MMP9 and promoted the metastatic growth of prostate cancer cells. Moreover, ALDH(high) tumor cells expressing elevated levels of aromatase stimulated tumor/host estrogen production and acquired a growth advantage in the presence of host bone marrow cells. Overall, these findings suggest that local production of steroids and MMPs in the bone marrow may provide a suitable microenvironment for ALDH(high) prostate cancer cells to establish metastatic growths, offering new approaches to therapeutically target bone metastases. Cancer Res; 76(8); 2453-64. ©2016 AACR. PMID:26921336

  19. 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.

  20. 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

  1. Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model

    Directory of Open Access Journals (Sweden)

    Chang Chin-Pao

    2011-01-01

    Full Text Available Abstract Background Hedgehog signalling has been implicated in prostate tumorigenesis in human subjects and mouse models, but its effects on transforming normal basal/stem cells toward malignant cancer stem cells remain poorly understood. Methods We produced pCX-shh-IG mice that overexpress Hedgehog protein persistently in adult prostates, allowing for elucidation of the mechanism during prostate cancer initiation and progression. Various markers were used to characterize and confirm the transformation of normal prostate basal/stem cells into malignant cancer stem cells under the influence of Hedgehog overexpression. Results The pCX-shh-IG mice developed prostatic intraepithelial neoplasia (PIN that led to invasive and metastatic prostate cancers within 90 days. The prostate cancer was initiated through activation of P63+ basal/stem cells along with simultaneous activation of Hedgehog signalling members, suggesting that P63+/Patch1+ and P63+/Smo+ cells may serve as cancer-initiating cells and progress into malignant prostate cancer stem cells (PCSCs. In the hyperplastic lesions and tumors, the progeny of PCSCs differentiated into cells of basal-intermediate and intermediate-luminal characteristics, whereas rare ChgA+ neuroendocrine differentiation was seen. Furthermore, in the metastatic loci within lymph nodes, kidneys, and lungs, the P63+ PCSCs formed prostate-like glandular structures, characteristic of the primitive structures during early prostate development. Besides, androgen receptor (AR expression was detected heterogeneously during tumor progression. The existence of P63+/AR-, CK14+/AR- and CD44+/AR- progeny indicates direct procurement of AR- malignant cancer trait. Conclusions These data support a cancer stem cell scenario in which Hedgehog signalling plays important roles in transforming normal prostate basal/stem cells into PCSCs and in the progression of PCSCs into metastatic tumor cells.

  2. 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.

  3. Should docetaxel be standard of care for patients with metastatic hormone-sensitive prostate cancer? Pro and contra.

    Science.gov (United States)

    Fizazi, K; Jenkins, C; Tannock, I F

    2015-08-01

    Following the results of the TAX-327 study, questions have been raised as to whether administering chemotherapy to men with prostate cancer before symptomatic disease progression when receiving standard hormonal treatment can improve the duration and quality of patient survival. The GETUG-AFU-15 and CHAARTED studies both assessed the efficacy and tolerability of androgen deprivation therapy (ADT) with or without docetaxel in men with metastatic hormone-naive prostate cancer. Both studies included a mix of patients with de novo metastatic disease (∼75%) and patients who developed metastases following treatment of localized disease. A short course of ADT was allowed in both trials prior to accrual. Key differences between the two studies include the number of patients with high-volume metastases (GETUG-AFU-15: 52%; CHAARTED: 65%) and number of docetaxel cycles (GETUG-AFU-15: up to nine cycles; CHAARTED six cycles). Both studies reported an improvement in progression-free survival with docetaxel plus ADT versus ADT alone. The GETUG-AFU-15 did not find a significant difference in the primary end point of overall survival (OS) {hazard ratio (HR) 0.9 [95% confidence interval (CI) 0.7-1.2]; P = 0.44} for ADT plus docetaxel versus ADT alone. The CHAARTED study met the primary end point of OS [HR 0.61 (95% CI 0.47-0.80); P = 0.0003], and in a subset analysis reported the greatest improvement in OS for patients with high-volume disease [HR 0.60 (95% CI 0.45-0.81); P = 0.0006]. The following article debates the results from the GETUG-AFU-15 and CHAARTED studies and asks whether medical practice should be changed for patients with metastatic hormone-naive prostate cancer based on the results of one positive study. PMID:26002607

  4. The Effects of Social Support on Health-Related Quality of Life of Patients with Metastatic Prostate Cancer.

    Science.gov (United States)

    Colloca, Giuseppe; Colloca, Pasquale

    2016-06-01

    Patients with metastatic prostate cancer (PC) live longer than patients with metastatic tumours of other sites. Consequently, their social network can influence their quality of life (QoL) during a remarkable life span. The aim of this article is to present the findings of a systematic review of the studies that focused on social network supporting the quality of life of these patients. A systematic review for studies meeting specific criteria was undertaken on three databases. Some level of unmet psychological needs was present in 54 % of the patients. Depression and fatigue are highly prevalent, and the dyads, patient and partner, are at higher risk for distress symptoms. The efforts of individuals to cope with metastatic PC appear influenced by adaptative skills and specific types of family support. Psychological and relational problems predominate in the hormone-sensitive stage and are increasingly replaced by physical symptoms, social and spiritual needs in the later stages. In the early castration-resistant stage, patients will discuss with their doctors information about drugs, control of side effects and treatment strategies. In metastatic PC patients, needs change during the course of the disease. Social support plays a major role in maintaining or disrupting QoL and in the efficacy of psychosocial treatments. The trajectory of disease and its effect on the reduced QoL over the entire life expectancy should be kept in mind by health system providers and social workers. PMID:26174117

  5. 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.

  6. Enzalutamide treatment in patients with metastatic castration-resistant prostate cancer progressing after chemotherapy and abiraterone acetate

    DEFF Research Database (Denmark)

    Thomsen, Frederik Birkebaek; Røder, Martin Andreas; Rathenborg, Per;

    2014-01-01

    OBJECTIVE: The aim of this study was to record prostate-specific antigen (PSA) response and overall survival (OS) for a group of metastatic castration-resistant prostate cancer (mCRPC) patients treated with enzalutamide following progression after abiraterone treatment in the post-chemotherapy......%). Forty-six percent had a greater than 30% decrease in PSA. The PSA response to enzalutamide did not correlate with the number of prior cancer treatments (p = 0.57), time from diagnosis to mCRPC (p = 0.11) or prior response to docetaxel (p = 0.67). However, patients treated with second line cabazitaxel...... marked fall in PSA following enzalutamide therapy in post-chemotherapy mCRPC patients compared with reported results in randomized trials. Larger prospective studies of sequencing are warranted....

  7. 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.

  8. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer

    OpenAIRE

    Hussain, Maha; Carducci, Michael A.; Slovin, Susan; Cetnar, Jeremy; Qian, Jiang; McKeegan, Evelyn M.; Refici-Buhr, Marion; Chyla, Brenda; Shepherd, Stacie P.; Giranda, Vincent L.; Alumkal, Joshi J.

    2014-01-01

    Androgen receptor-mediated transcription is directly coupled with the induction of DNA damage, and castration-resistant tumor cells exhibit increased activity of poly (ADP-ribose) polymerase (PARP)-1, a DNA repair enzyme. This study assessed the efficacy and safety of low dose oral PARP inhibitor veliparib (ABT-888) and temozolomide (TMZ) in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) in a single-arm, open-label, pilot study. Patients with mCRPC ...

  9. 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.

  10. MOR209/ES414, a Novel Bispecific Antibody Targeting PSMA for the Treatment of Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Hernandez-Hoyos, Gabriela; Sewell, Toddy; Bader, Robert; Bannink, Jeannette; Chenault, Ruth A; Daugherty, Mollie; Dasovich, Maria; Fang, Hang; Gottschalk, Rebecca; Kumer, John; Miller, Robert E; Ravikumar, Padma; Wiens, Jennifer; Algate, Paul A; Bienvenue, David; McMahan, Catherine J; Natarajan, Sateesh K; Gross, Jane A; Blankenship, John W

    2016-09-01

    Treatment of metastatic, castration-resistant prostate cancer (mCRPC) remains a highly unmet medical need and current therapies ultimately result in disease progression. Immunotherapy is a rapidly growing approach for treatment of cancer but has shown limited success to date in the treatment of mCRPC. We have developed a novel humanized bispecific antibody, MOR209/ES414, built on the ADAPTIR (modular protein technology) platform, to redirect T-cell cytotoxicity toward prostate cancer cells by specifically targeting T cells through CD3ε to prostate cancer cells expressing PSMA (prostate-specific membrane antigen). In vitro cross-linking of T cells with PSMA-expressing tumor cells by MOR209/ES414 triggered potent target-dependent tumor lysis and induction of target-dependent T-cell activation and proliferation. This activity occurred at low picomolar concentrations of MOR209/ES414 and was effective at low T-effector to tumor target cell ratios. In addition, cytotoxic activity was equivalent over a wide range of PSMA expression on target cells, suggesting that as few as 3,700 PSMA receptors per cell are sufficient for tumor lysis. In addition to high sensitivity and in vitro activity, MOR209/ES414 induced limited production of cytokines compared with other bispecific antibody formats. Pharmacokinetic analysis of MOR209/ES414 demonstrated a serum elimination half-life in NOD/SCID γ (NSG) mice of 4 days. Administration of MOR209/ES414 in murine xenograft models of human prostate cancer significantly inhibited tumor growth, prolonged survival, and decreased serum prostate-specific antigen levels only in the presence of adoptively transferred human T cells. On the basis of these preclinical findings, MOR209/ES414 warrants further investigation as a potential therapeutic for the treatment of CRPC. Mol Cancer Ther; 15(9); 2155-65. ©2016 AACR. PMID:27406985

  11. Prognostic Significance of PSA, Gleason Score, Bone Metastases in Patients with Metastatic Prostate Cancer Under Palliative Androgen Deprivation Treatment

    International Nuclear Information System (INIS)

    Objective: The aim of this study was to evaluate the prognostic significance of each of the following in the development and progression of hormonal refractory disease in patients with metastatic prostate cancer under hormonal palliative treatment: The initial serum level prostate specific antigen (PSA), the Gleason score (GS), the presence of bone metastases with or without visceral metastases, and the PSA decline. Patients and Methods: During the time period from January 2005 to December 2008, a total of 92 patients with newly diagnosed, histologically confirmed metastatic prostate cancer (MPC) were under palliative androgen deprivation therapy. The age range was 52 to 85 years with a mean age of 66.2±7.9 years. MPC was diagnosed histologically after transrectal ultrasonography guided biopsy. The Gleason score assessment was determined by low power microscopic examination. Metastases were confirmed by positive bone scintigraphy with 925 MBq 99mTc-MDP using a tomographic gamma camera, computerized axial tomography or magnetic resonance imagining. Measurements of PSA levels were conducted by the radioimmunoassay method. The influences of the following prognostic factors were evaluated: The initial serum level of prostate specific antigen (PSA), the Gleason score (GS), the presence of bone metastases with or without visceral metastases, and the PSA decline, on the time to disease progression. Results: The time to progression was significantly delayed in patients with initial PSA level £50 ng/ml (median: 32 months), Gleason Score £7 (median: 33 months), bone metastases only (median: 30 months) and PSA level normalization within 6 months (median: 30 months) compared to that of patients with initial PSA level >50 ng/ml (median: 24 months), Gleason Score >7 (median: 24 months), bone, distant lymph nodes and/or visceral metastases (median: 24 months), PSA level decline (median: 18 months) (p-values were 0.002, 6 sites bone metastases (median: 28 months) (p=0

  12. Early outcome prediction on 18F-fluorocholine PET/CT in metastatic castration-resistant prostate cancer patients treated with abiraterone

    OpenAIRE

    De Giorgi, Ugo; Caroli, Paola; Burgio, Salvatore L.; Menna, Cecilia; Conteduca, Vincenza; Bianchi, Emanuela; Fabbri, Francesca; Carretta, Elisa; Amadori, Dino; Paganelli, Giovanni; Matteucci, Federica

    2014-01-01

    Objective: We investigated the role of 18F-fluorocholine positron emission tomography/computed tomography (FCH-PET/CT) in the early evaluation of abiraterone and outcome prediction in patients with metastatic castration-resistant prostate cancer (CRPC). Patient and methods: Forty-three patients with metastatic CRPC progressing after docetaxel received abiraterone 1,000 mg daily with prednisone 5 mg twice daily. Patients were evaluated monthly for serological PSA response and safety. FCH-PET/C...

  13. Pain, PSA flare, and bone scan response in a patient with metastatic castration-resistant prostate cancer treated with radium-223, a case report

    International Nuclear Information System (INIS)

    Radium-223 has been shown to improve overall survival in men with metastatic castration-resistant prostate cancer with symptomatic bone metastases. The bone scan response to radium-223 has only been described in one single center trial of 14 patients, none of whom achieved the outstanding bone scan response presented in the current case. In this case report, we describe a 75 year-old white man with extensively pre-treated metastatic castration-resistant prostate cancer and symptomatic bone metastases who experienced a flare in pain and prostate-specific antigen, followed by dramatic clinical (pain), biochemical (prostate-specific antigen), and imaging (bone scan) response. The flare phenomena and bone scan response we observed have not previously been described with radium-223. This case suggests that the degree and duration of bone scan response may be predictive of overall survival benefit

  14. A review of continuous vs intermittent androgen deprivation therapy: Redefining the gold standard in the treatment of advanced prostate cancer. Myths, facts and new data on a perpetual dispute

    Directory of Open Access Journals (Sweden)

    Zisis Kratiras

    2014-01-01

    Full Text Available Objectives: To review the literature and present new data of continuous androgen deprivation therapy (ADT vs intermittent androgen deprivation (IAD as therapies for prostate cancer in terms of survival and quality of life and clarify practical issues in the use of IAD. Materials and Methods: We conducted a systematic search on Medline and Embase databases using “prostatic neoplasm” and “intermittent androgen deprivation” as search terms. We reviewed meta-analyses, randomised controlled trials, reviews, clinical trials and practise guidelines written in English from 2000 and onwards until 01/04/2013. Ten randomized controlled trials were identified. Seven of them published extensive data and results randomizing 4675 patients to IAD versus CAD. Data from the other three randomized trials were limited. Results: Over the last years studies confirmed that IAD is an effective alternative approach to hormonal deprivation providing simultaneously several potential benefits in terms of quality of life and cost effectiveness. Thus, in patients with non metastatic, advanced prostate cancer IAD could be used as standard treatment, while in metastatic prostate cancer IAD role still remains ambiguous. Conclusions: Nowadays, revaluation of the gold standard of ADT in advanced prostate cancer appears essential. Recent data established that IAD should no longer be considered as investigational, since its effectiveness has been proven, especially in patients suffering from non-metastatic advanced prostate cancer.

  15. A Joint Model for the Kinetics of CTC Count and PSA Concentration During Treatment in Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Wilbaux, M; Tod, M; De Bono, J; Lorente, D; Mateo, J; Freyer, G; You, B; Hénin, E

    2015-05-01

    Assessment of treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) is limited by frequent nonmeasurable bone metastases. The count of circulating tumor cells (CTCs) is a promising surrogate marker that may replace the widely used prostate-specific antigen (PSA). The purpose of this study was to quantify the dynamic relationships between the longitudinal kinetics of these markers during treatment in patients with mCRPC. Data from 223 patients with mCRPC treated by chemotherapy and/or hormonotherapy were analyzed for up to 6 months of treatment. A semimechanistic model was built, combining the following several pharmacometric advanced features: (1) Kinetic-Pharmacodynamic (K-PD) compartments for treatments (chemotherapy and hormonotherapy); (2) a latent variable linking both marker kinetics; (3) modeling of CTC kinetics with a cell lifespan model; and (4) a negative binomial distribution for the CTC random sampling. Linked with survival, this model would potentially be useful for predicting treatment efficacy during drug development or for therapeutic adjustment in treated patients. PMID:26225253

  16. 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.

  17. 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

  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. Effect of abiraterone acetate treatment on the quality of life of patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy

    NARCIS (Netherlands)

    Harland, S.; Staffurth, J.; Molina, A.; Hao, Y.; Gagnon, D.D.; Sternberg, C.N.; Cella, D.; Fizazi, K.; Logothetis, C.J.; Kheoh, T.; Haqq, C.M.; Bono, J.S. de; Scher, H.I.; Mulders, P.F.

    2013-01-01

    BACKGROUND: In a recent randomised, double-blind, phase III clinical trial among 1195 patients with metastatic castration-resistant prostate cancer (mCRPC) who had failed docetaxel chemotherapy, abiraterone acetate was shown to significantly prolong overall survival compared with prednisone alone. H

  20. 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

  1. 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 with progre...

  2. 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....

  3. 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...

  4. 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% ...

  5. Recent advances in treatment for Benign Prostatic Hyperplasia

    OpenAIRE

    van Rij, Simon; Gilling, Peter

    2015-01-01

    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 ...

  6. 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

  7. Development of a Second-Generation Antiandrogen for Treatment of Advanced Prostate Cancer

    OpenAIRE

    Tran, Chris; Ouk, Samedy; Clegg, Nicola J.; Chen, Yu; Watson, Philip A.; Arora, Vivek; Wongvipat, John; Smith-Jones, Peter M.; Yoo, Dongwon; Kwon, Andrew; Wasielewska, Teresa; Welsbie, Derek; Chen, Charlie; Higano, Celestia S.; Beer, Tomasz M

    2009-01-01

    Metastatic prostate cancer is treated with drugs that antagonize androgen action but most patients progress to a more aggressive form of the disease called castration-resistant prostate cancer, driven by elevated expression of the androgen receptor. Here we characterize the diarylthiohydantoins RD162 and MDV3100, two compounds optimized from a screen for non-steroidal antiandrogens that retain activity in the setting of increased androgen receptor expression. Both compounds bind to the androg...

  8. 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

  9. Genistein increases epidermal growth factor receptor signaling and promotes tumor progression in advanced human prostate cancer.

    Directory of Open Access Journals (Sweden)

    Hisae Nakamura

    Full Text Available Genistein is an isoflavone found in soy, and its chemo-preventive and -therapeutic effects have been well established from in vitro studies. Recently, however, its therapeutic actions in vivo have been questioned due to contradictory reports from animal studies, which rely on rodent models or implantation of cell lines into animals. To clarify in vivo effects of genistein in advanced prostate cancer patients, we developed a patient-derived prostate cancer xenograft model, in which a clinical prostatectomy sample was grafted into immune deficient mice. Our results showed an increased lymph node (LN and secondary organ metastases in genistein-treated mice compared to untreated controls. Interestingly, invasive malignant cells aggregated to form islands/micrometastasis only in the secondary organs of the genistein-treated groups, not in the untreated control group. To understand the underlying mechanism for metastatic progression, we examined cell proliferation and apoptosis on paraffin-sections. Immunohistological data show that tumors of genistein-treated groups have more proliferating and fewer apoptotic cancer cells than those of the untreated group. Our immunoblotting data suggest that increased proliferation and metastasis are linked to enhanced activities of tyrosine kinases, EGFR and its downstream Src, in genistein-treated groups. Despite the chemopreventive effects proposed by earlier in vitro studies, the cancer promoting effect of genistein observed here suggests the need for careful selection of patients and safer planning of clinical trials.

  10. The IGR-CaP1 Xenograft Model Recapitulates Mixed Osteolytic/Blastic Bone Lesions Observed in Metastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Nader Al Nakouzi

    2012-05-01

    Full Text Available Bone metastases have a devastating impact on quality of life and bone pain in patients with prostate cancer and decrease survival. Animal models are important tools in investigating the pathogenesis of the disease and in developing treatment strategies for bone metastases, but few animal models recapitulate spontaneous clinical bone metastatic spread. In the present study, IGR-CaP1, a new cell line derived from primary prostate cancer, was stably transduced with a luciferase-expressing viral vector to monitor tumor growth in mice using bioluminescence imaging. The IGR-CaP1 tumors grew when subcutaneously injected or when orthotopically implanted, reconstituted the prostate adenocarcinoma with glandular acini-like structures, and could disseminate to the liver and lung. Bone lesions were detected using bioluminescence imaging after direct intratibial or intracardiac injections. Anatomic bone structure assessed using high-resolution computed tomographic scans showed both lytic and osteoblastic lesions. Technetium Tc 99m methylene diphosphonate micro single-photon emission computed tomography confirmed the mixed nature of the lesions and the intensive bone remodeling. We also identified an expression signature for responsiveness of IGR-CaP1 cells to the bone microenvironment, namely expression of CXCR4, MMP-9, Runx2, osteopontin, osteoprotegerin, ADAMTS14, FGFBP2, and HBB. The IGR-CaP1 cell line is a unique model derived from a primary tumor, which can reconstitute human prostate adenocarcinoma in animals and generate experimental bone metastases, providing a novel means for understanding the mechanisms of bone metastasis progression and allowing preclinical testing of new therapies.

  11. 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.

  12. 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.

  13. Epigenomic Alterations in Localized and Advanced Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Pei-Chun Lin

    2013-04-01

    Full Text Available Although prostate cancer (PCa is the second leading cause of cancer death among men worldwide, not all men diagnosed with PCa will die from the disease. A critical challenge, therefore, is to distinguish indolent PCa from more advanced forms to guide appropriate treatment decisions. We used Enhanced Reduced Representation Bisulfite Sequencing, a genome-wide high-coverage single-base resolution DNA methylation method to profile seven localized PCa samples, seven matched benign prostate tissues, and six aggressive castration-resistant prostate cancer (CRPC samples. We integrated these data with RNA-seq and whole-genome DNA-seq data to comprehensively characterize the PCa methylome, detect changes associated with disease progression, and identify novel candidate prognostic biomarkers. Our analyses revealed the correlation of cytosine guanine dinucleotide island (CGI-specific hypermethylation with disease severity and association of certain breakpoints (deletion, tandem duplications, and interchromosomal translocations with DNA methylation. Furthermore, integrative analysis of methylation and single-nucleotide polymorphisms (SNPs uncovered widespread allele-specific methylation (ASM for the first time in PCa. We found that most DNA methylation changes occurred in the context of ASM, suggesting that variations in tumor epigenetic landscape of individuals are partly mediated by genetic differences, which may affect PCa disease progression. We further selected a panel of 13 CGIs demonstrating increased DNA methylation with disease progression and validated this panel in an independent cohort of 20 benign prostate tissues, 16 PCa, and 8 aggressive CRPCs. These results warrant clinical evaluation in larger cohorts to help distinguish indolent PCa from advanced disease.

  14. 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.

  15. A Phase 2 Trial of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer and without Prior Chemotherapy (JPN-201 Study)

    Science.gov (United States)

    Matsubara, Nobuaki; Uemura, Hirotsugu; Satoh, Takefumi; Suzuki, Hiroyoshi; Nishiyama, Tsutomu; Uemura, Hiroji; Hashine, Katsuyoshi; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective Abiraterone acetate has been approved in >70 countries for chemotherapy-naïve metastatic castration-resistant prostate cancer patients. Efficacy and safety of abiraterone acetate (1000 mg/once daily) with prednisolone (5 mg/twice daily) in chemotherapy-naïve Japanese patients with metastatic castration-resistant prostate cancer was evaluated. Methods Men, ≥20 years, with prostate-specific antigen levels of ≥5 ng/ml and evidence of progression were enrolled in this Phase 2, multicenter, open-label study. Primary efficacy endpoint was proportion of patients achieving a prostate-specific antigen decline of ≥50% from baseline (prostate-specific antigen response) after 12 week of treatment. Secondary efficacy endpoints and safety were assessed. Results A confirmed prostate-specific antigen response was observed in 29/48 (60.4%) patients by week 12; lower limit of two-sided 90% confidence interval was >35% (threshold response rate), demonstrating efficacy of abiraterone acetate. Secondary efficacy endpoints: prostate-specific antigen response rate during treatment period: 62.5%; objective radiographic response, partial response: 4/18 (22.2%) patients; complete response: none; stable disease: 11/18 (61.1%) patients; median percent change in prostate-specific antigen level from baseline at Week 12: −66.62%. Median prostate-specific antigen response duration and progression-free survival were not reached, and median radiographic progression-free survival was 253 days. Of 31/48 (64.6%) patients experienced adverse events of special interest; most common was hepatic function abnormality (37.5%, Grade 3: 10.4%). One Grade 3 hypertension was the only mineralocorticoid adverse event >Grade 1/2. Conclusions Efficacy of abiraterone acetate plus prednisolone was demonstrated by decline in prostate-specific antigen levels with evidence of antitumor activity by radiography in Japanese patients with chemotherapy-naïve metastatic castration-resistant prostate

  16. 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....

  17. 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....

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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....

  3. 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...

  4. 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...

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

    International Nuclear Information System (INIS)

    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 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 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.

  6. A Phase 2 Study of Abiraterone Acetate in Japanese Men with Metastatic Castration-resistant Prostate Cancer Who Had Received Docetaxel-based Chemotherapy

    Science.gov (United States)

    Satoh, Takefumi; Uemura, Hiroji; Tanabe, Kazunari; Nishiyama, Tsutomu; Terai, Akito; Yokomizo, Akira; Nakatani, Tatsuya; Imanaka, Keiichiro; Ozono, Seiichiro; Akaza, Hideyuki

    2014-01-01

    Objective In this Phase 2 multicenter study the efficacy and safety of oral abiraterone acetate (1000 mg/once daily) plus prednisolone (5 mg/twice daily) was evaluated in metastatic castration-resistant prostate cancer patients from Japan who had previously received docetaxel-based chemotherapy. Methods Men (aged ≥20 years) with metastatic castration-resistant prostate cancer (prostate-specific antigen levels: ≥5 ng/ml), who had received 1 or 2 cytotoxic chemotherapies (with ≥1 regimen being docetaxel) for prostate cancer, were enrolled in this open-label, single-arm study. Primary efficacy endpoint was proportion of patients achieving a ≥50% prostate-specific antigen decline from baseline (prostate-specific antigen response rate) after 12-week treatment. Safety and pharmacokinetics were also assessed. Results Confirmed prostate-specific antigen response rate by Week 12 was 28.3% (90% confidence interval: 17.6%; 41.1%) or 13 out of 46 (full analysis set) treated patients. However, total prostate-specific antigen response rate including confirmed and unconfirmed responses was 34.8% (90% confidence interval: 23.2%; 47.9%). Secondary efficacy endpoints and outcomes were: improvement in Eastern Cooperative Oncology Group performance status score by ≥1 unit: 7/16 patients (43.8%); objective radiographic response: complete response, partial response and stable disease in 0, 1/22 (4.5%) and 9/22 (40.9%) patients, respectively; pain palliation response: 9/16 (56.3%) patients. The most common adverse events (>20% patients) were upper respiratory tract infection (13/47, 27.7% patients) and hepatic function abnormal (10/47, 21.3% patients, Grade 3: 8.5%). All mineralocorticoid-related toxicities were Grade 1/2. Conclusions Abiraterone acetate plus prednisolone showed favorable efficacy in metastatic castration-resistant prostate cancer Japanese patients who had received chemotherapy. Abiraterone acetate plus prednisolone had an acceptable safety profile. Clinical

  7. 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.

  8. Clinical observation on docetaxel plus S1 in the treatment of advanced metastatic breast cancer

    Institute of Scientific and Technical Information of China (English)

    Jian Cao; Ping Sun

    2013-01-01

    Objective: The aim of our study was to observe the efficacy and adverse reactions of docetaxel plus S1 in patients with advanced metastatic breast cancer. Methods: Twenty-seven patients with advanced metastatic breast cancer receiving docetaxel plus S1 in our hospital were analyzed. The efficacy and safety were evaluated according to RECIST and NCI CTC 3.0. Results: The clinical efficacy and toxicity were evaluated in all the 27 patients, including 1 case of CR, 12 of PR, 6 of SD, and 8 of PD (ORR = 48.1%, CBR = 70.3%). The median time to tumor progression (mTTP) was 7.3 months. No IV degree of adverse reaction was observed in the observation group. Most adverse reactions were degrees I and II, the most common reactions were neutropenia (59.3%), abnormal liver function (33.3%), gastrointestinal adverse events (29.6 %) and stomatitis (7.4%). Conclusion: With good efficacy and low toxicity, docetaxel plus S1 could be administered in the treatment of advanced metastatic breast cancer.

  9. The PREVAIL trial of enzalutamide in men with chemotherapy-naïve, metastatic castration-resistant prostate cancer: Post hoc analysis of Korean patients

    OpenAIRE

    Kim, Choung-Soo; Theeuwes, Ad; Kwon, Dong Deuk; Choi, Young Deuk; Chung, Byung Ha; Lee, Hyun Moo; Lee, Kang Hyun; Lee, Sang Eun

    2016-01-01

    Purpose This post hoc analysis evaluated treatment effects, safety, and pharmacokinetics of enzalutamide in Korean patients in the phase 3, double-blind, placebo-controlled PREVAIL trial. Materials and Methods Asymptomatic or mildly symptomatic chemotherapy-naive men with metastatic castration-resistant prostate cancer that progressed on androgen deprivation therapy received 160 mg/d oral enzalutamide or placebo (1:1) until death or discontinuation due to radiographic progression or skeletal-...

  10. Abiraterone acetate in patients with metastatic castration-resistant prostate cancer: long term outcome of the Temporary Authorization for Use programme in France

    OpenAIRE

    Houédé, Nadine; Beuzeboc, Philippe; Gourgou, Sophie; Tosi, Diego; Moise, Laura; Gravis, Gwenaëlle; Delva, Remy; Fléchon, Aude; Latorzeff, Igor; Ferrero, Jean-Marc; Oudard, Stéphane; Tartas, Sophie; Laguerre, Brigitte; Topart, Delphine; Roubaud, Guilhem

    2015-01-01

    AbstractBackgroundCOU-AA-301 trial has proved that abiraterone acetate (AA), a selective inhibitor of androgen biosynthesis, improved overall survival (OS) of patients with metastatic castration resistant prostate cancer (mCRPC) after a first line of docetaxel. Based on this result, a Temporary Authorization for Use (TAU) was performed between December 2010 and July 2011 to provide patients with mCRPC the opportunity to receive AA before its commercialization. The aim of this study was to eva...

  11. 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.

  12. 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

  13. Zoledronic acid in the management of metastatic bone disease

    Directory of Open Access Journals (Sweden)

    Thomas J Polascik

    2008-03-01

    Full Text Available Thomas J Polascik, Vladimir MouravievDuke Prostate Center and Division of Urologic Surgery, Duke University Medical Center, Durham, NC, USAAbstract: Many patients with advanced cancer experience decreased bone strength due to metastatic foci, underlying osteoporosis and/or cancer treatment induced bone loss. The clinical consequences of metastatic disease involving the skeleton are widespread. This review focuses on the efficacy, pharmacology, and safety when using intravenous biphosphonate such a zoledronic acid for cancer bone metastases. Zoledronic acid is the gold standard for the medical management of metastatic bone disease. The indications for treatment include prevention of skeletal relevant events (SRE, osteoporotic complications, and palliation of bone pain, among others. Zoledronic acid is the only bisphosphonate effective in decreasing SREs associated with bone metastases from advanced renal cell carcinoma and prostate cancer. Regarding prostate cancer, zoledronic acid effectively prevents both bone loss in patients with locally advanced disease receiving androgen deprivation therapy and SREs in men with hormone-refractory or hormonesensitive metastatic disease. Zoledronic acid has an acceptable safety profile and tolerability, and has been effective at significantly decreasing the incidence, delaying the onset, and reducing the overall risk of experiencing an SRE compared to placebo. It is the only bisphosphonate currently approved for the prevention and treatment of skeletal complications in patients with bone metastases due to all solid tumors.Keywords: zoledronic acid, metastatic bone disease, osteoporosis, skeletal relevant events, advanced prostate cancer

  14. 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

    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....... 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...... 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

  15. Adenocarcinoma of the prostate and metastatic medullary compression. A retrospective study of 22 patients

    DEFF Research Database (Denmark)

    Honnens de Lichtenberg, M; Kvist, E; Hjortberg, P;

    1992-01-01

    A retrospective study of 709 patients with prostatic cancer was carried out. Twenty-two developed medullary cord compression (an incidence of 3%). All but two of the 22 patients were treated by radiation and 10 had additional hormonal treatment. Ten had some benefit from the treatment, but only 2...... of 19 regained their ability to walk. The need for immediate diagnosis and treatment is stressed....

  16. Prostate cancer specific integrin αvβ3 modulates bone metastatic growth and tissue remodeling

    OpenAIRE

    McCabe, NP; De, S.; Vasanji, A; Brainard, J; Byzova, TV

    2007-01-01

    The management of pain and morbidity owing to the spreading and growth of cancer within bone remains to be a paramount problem in clinical care. Cancer cells actively transform bone, however, the molecular requirements and mechanisms of this process remain unclear. This study shows that functional modulation of the αvβ3 integrin receptor in prostate cancer cells is required for progression within bone and determines tumor-induced bone tissue transformation. Using histology and quantitative mi...

  17. Metronomic cyclophosphamide therapy in hormone-naive patients with non-metastatic biochemical recurrent prostate cancer: a phase II trial.

    Science.gov (United States)

    Calcagno, Fabien; Mouillet, Guillaume; Adotevi, Olivier; Maurina, Tristan; Nguyen, Thierry; Montcuquet, Philippe; Curtit, E; Kleinclauss, F; Pivot, Xavier; Borg, Christophe; Thiery-Vuillemin, Antoine

    2016-08-01

    After curative local therapy, biochemical recurrence is a mode of relapse among patient with prostate cancer (PC). Deferring androgen deprivation therapy (ADT) or offering non-hormonal therapies may be an appropriate option for these non-symptomatic patients with no proven metastases. Metronomic cyclophosphamide (MC) has shown activity in metastatic PC setting and was chosen to be assessed in biochemical relapse. This prospective single-arm open-label phase II study was conducted to evaluate MC regimen in patients with biochemical recurrent PC. MC was planned to be administered orally at a daily dose of 50 mg for 6 months. Primary endpoint was PSA response. Thirty-eight patients were included and treated. Median follow-up was 45.5 months (range 17-100). Among them, 14 patients (37 %) achieved PSA stabilisation and 22 patients (58 %) experienced PSA progression. Response rate was 5 % with one complete response (2.6 %), and 1 partial response with PSA decrease >50 % (2.6 %). The median time until androgen deprivation therapy initiation was around 15 months. The treatment was well tolerated. Neither grade 3-4 toxicity nor serious adverse events were observed. This first prospective clinical trial with MC therapy in patients with non-metastatic biochemical recurrence of PC displayed modest efficacy when measured with PSA response rate, without significant toxicity. It might offer a new safe and non-expensive option to delay initiation of ADT. These results would need to be confirmed with larger prospective randomised trials. PMID:27400698

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

    International Nuclear Information System (INIS)

    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. This review describes the mechanism, radiobiology, and preclinical development of 223Ra and discusses the clinical data currently available regarding its safety and efficacy profile. 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. 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 agents

  19. 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

  20. 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

  1. The use of circulating tumor cells in guiding treatment decisions for patients with metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Onstenk, Wendy; de Klaver, Willemijn; de Wit, Ronald; Lolkema, Martijn; Foekens, John; Sleijfer, Stefan

    2016-05-01

    The therapeutic landscape of metastatic castration-resistant prostate cancer (mCRPC) has drastically changed over the past decade with the advent of several new anti-tumor agents. Oncologists increasingly face dilemmas concerning the best treatment sequence for individual patients since most of the novel compounds have been investigated and subsequently positioned either pre- or post-docetaxel. A currently unmet need exists for biomarkers able to guide treatment decisions and to capture treatment resistance at an early stage thereby allowing for an early change to an alternative strategy. Circulating tumor cells (CTCs) have in this context intensively been investigated over the last years. The CTC count, as determined by the CellSearch System (Janssen Diagnostics LLC, Raritan, NJ), is a strong, independent prognostic factor for overall survival in patients with mCRPC at various time points during treatment and, as an early response marker, outperforms traditional response evaluations using serum prostate specific antigen (PSA) levels, scintigraphy as well as radiography. The focus of research is now shifting toward the predictive value of CTCs and the use of the characterization of CTCs to guide the selection of treatments with the highest chance of success for individual patients. Recently, the presence of the androgen receptor splice variant 7 (AR-V7) has been shown to be a promising predictive factor. In this review, we have explored the clinical value of the enumeration and characterization of CTCs for the treatment of mCRPC and have put the results obtained from recent studies investigating the prognostic and predictive value of CTCs into clinical perspective. PMID:27107266

  2. 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.

  3. Non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for advanced prostate cancer: a Cochrane systematic review.

    Science.gov (United States)

    Kunath, Frank; Grobe, Henrik R; Rücker, Gerta; Motschall, Edith; Antes, Gerd; Dahm, Philipp; Wullich, Bernd; Meerpohl, Joerg J

    2015-07-01

    To assess the effects of non-steroidal antiandrogen monotherapy compared with luteinizing hormone-releasing hormone agonists or surgical castration monotherapy for treating advanced hormone-sensitive stages of prostate cancer. We searched the Cochrane Prostatic Diseases and Urologic Cancers Group Specialized Register (PROSTATE), the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science with Conference Proceedings, three trial registries and abstracts from three major conferences to 23 December 2013, together with reference lists, and contacted selected experts in the field and manufacturers. We included randomized controlled trials comparing non-steroidal antiandrogen monotherapy with medical or surgical castration monotherapy for men in advanced hormone-sensitive stages of prostate cancer. Two review authors independently examined full-text reports, identified relevant studies, assessed the eligibility of studies for inclusion, extracted data and assessed risk of bias as well as quality of evidence according to the GRADE working group guidelines. We used Review Manager 5.2 for data synthesis and the fixed-effect model as primary analysis (when heterogeneity was low with I(2) cancer-specific survival and biochemical progression remained unclear. Non-steroidal antiandrogen monotherapy compared with medical or surgical castration monotherapy for advanced prostate cancer is less effective in terms of overall survival, clinical progression, treatment failure and treatment discontinuation resulting from adverse events. Evidence quality was rated as moderate according to GRADE; therefore, further research is likely to have an important impact on results for patients with advanced but non-metastatic prostate cancer treated with non-steroidal antiandrogen monotherapy. PMID:25523493

  4. Advanced prostatic carcinomas with low serum levels of prostate-specific antigen

    Directory of Open Access Journals (Sweden)

    Cerović Snežana J.

    2002-01-01

    Full Text Available The serum levels of prostate-specific antigen (PSA represent a significant diagnostic and monitoring parameter of prostatic carcinoma (PC. The aim of the study was to establish correlation of serum PSA level in addition to grade, histological type, and clinical stage of PC in patients with normal or intermediary PSA serum level. In 37 untreated PC patients with preoperative serum PSA levels ranging between 0.1 and 9.6 ng/ml, paraffin-embedded tissue and serum samples were immunohistological studied and immunoassay for PSA was done. The most representative was poorly differentiated PC with D stage In serum samples from PC patients 27 (73.7% normal (≤ 4.0 ng/ml, and 10 (27.3% intermediate (4.1-10 ng/ml PSA levels were found Immunohistochemistry, in 36 PC (97.3% had demonstrated the expression of PSA. Our study results had shown low serum PSA levels in some patients with advanced poorly differentiated PC.

  5. 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.

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

    OpenAIRE

    R. A. Gafanov

    2016-01-01

    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 prostat...

  7. 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

    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...... to receive bicalutamide in addition to their standard care and 611 to receive placebo. Median follow-up was 14.6years. Overall, 866 (71.1%) patients died, 428 (70.5%) in the bicalutamide arm and 438 (71.7%) in the placebo arm, p=0.87. Bicalutamide significantly improved OS in patient with locally advanced...... 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...

  8. Therapeutic Rationales, Progresses, Failures, and Future Directions for Advanced Prostate Cancer.

    Science.gov (United States)

    Wadosky, Kristine M; Koochekpour, Shahriar

    2016-01-01

    Patients with localized prostate cancer (PCa) have several therapeutic options with good prognosis. However, survival of patients with high-risk, advanced PCa is significantly less than patients with early-stage, organ-confined disease. Testosterone and other androgens have been directly linked to PCa progression since 1941. In this review, we chronicle the discoveries that led to modern therapeutic strategies for PCa. Specifically highlighted is the biology of androgen receptor (AR), the nuclear receptor transcription factor largely responsible for androgen-stimulated and castrate-recurrent (CR) PCa. Current PCa treatment paradigms can be classified into three distinct but interrelated categories: targeting AR at pre-receptor, receptor, or post-receptor signaling. The continuing challenge of disease relapse as CR and/or metastatic tumors, destined to occur within three years of the initial treatment, is also discussed. We conclude that the success of PCa therapies in the future depends on targeting molecular mechanisms underlying tumor recurrence that still may affect AR at pre-receptor, receptor, and post-receptor levels. PMID:27019626

  9. Targeting bone metabolism in patients with advanced prostate cancer: current options and controversies.

    Science.gov (United States)

    Todenhöfer, Tilman; Stenzl, Arnulf; Hofbauer, Lorenz C; Rachner, Tilman D

    2015-01-01

    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. PMID:25802521

  10. 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.

  11. 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

    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...

  12. An improved CTC isolation scheme for pairing with downstream genomics: Demonstrating clinical utility in metastatic prostate, lung and pancreatic cancer.

    Science.gov (United States)

    Premasekharan, Gayatri; Gilbert, Elizabeth; Okimoto, Ross A; Hamirani, Ashiya; Lindquist, Karla J; Ngo, Vy T; Roy, Ritu; Hough, Jeffrey; Edwards, Matthew; Paz, Rosa; Foye, Adam; Sood, Riddhi; Copren, Kirsten A; Gubens, Matthew; Small, Eric J; Bivona, Trever G; Collisson, Eric A; Friedlander, Terence W; Paris, Pamela L

    2016-09-28

    Improvements in technologies to yield purer circulating tumor cells (CTCs) will enable a broader range of clinical applications. We have previously demonstrated the use of a commercially available cell-adhesion matrix (CAM) assay to capture invasive CTCs (iCTCs). To improve the purity of the isolated iCTCs, here we used fluorescence-activated cell sorting (FACS) in combination with the CAM assay (CAM + FACS). Our results showed an increase of median purity from the CAM assay to CAM + FACS for the spiked-in cell lines and patient samples analyzed from three different metastatic cancer types: castration resistant prostate cancer (mCRPC), non-small cell lung cancer (mNSCLC) and pancreatic ductal adenocarcinoma cancer (mPDAC). Copy number profiles for spiked-in mCRPC cell line and mCRPC patient iCTCs were similar to expected mCRPC profiles and a matched biopsy. A somatic epidermal growth factor receptor (EGFR) mutation specific to mNSCLC was observed in the iCTCs recovered from EGFR(+) mNSCLC cell lines and patient samples. Next-generation sequencing (NGS) of spiked-in pancreatic cancer cell line and mPDAC patient iCTCs showed mPDAC common mutations. CAM + FACS iCTC enrichment enables multiple downstream genomic characterizations across different tumor types. PMID:27343980

  13. Advanced research on separating prostate cancer stem cells

    International Nuclear Information System (INIS)

    Prostate cancer is a common malignant tumor in male urinary system,and may easily develop into the hormone refractory prostate cancer which can hardly be cured. Recent studies had found that the prostate cancer stem cells may be the source of the prostate cancer's occurrence,development, metastasis and recurrence. The therapy targeting the prostate cancer stem cells may be the effective way to cure prostate cancer. But these cells is too low to be detected. The difficulty lies in the low separation efficiency of prostate cancer stem cell, so the effectively separating prostate cancer stem cells occupied the main position for the more in-depth research of prostate cancer stem cells. This paper reviews the research progress and existing problems on the several main separating methods of prostate cancer stem cells, includes the fluorescence activated cells sorting and magnetic activated cells sorting based on prostate cancer stem cell surface markers, the side-population sorting and serum-free medium sphere forming sorting based on prostate cancer stem cell's biology. (authors)

  14. 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

  15. Analytic Validation of the Automated Bone Scan Index as an Imaging Biomarker to Standardize Quantitative Changes in Bone Scans of Patients with Metastatic Prostate Cancer

    Science.gov (United States)

    Anand, Aseem; Morris, Michael J.; Kaboteh, Reza; Båth, Lena; Sadik, May; Gjertsson, Peter; Lomsky, Milan; Edenbrandt, Lars; Minarik, David; Bjartell, Anders

    2016-01-01

    A reproducible and quantitative imaging biomarker is needed to standardize the evaluation of changes in bone scans of prostate cancer patients with skeletal metastasis. We performed a series of analytic validation studies to evaluate the performance of the automated bone scan index (BSI) as an imaging biomarker in patients with metastatic prostate cancer. Methods Three separate analytic studies were performed to evaluate the accuracy, precision, and reproducibility of the automated BSI. Simulation study: bone scan simulations with predefined tumor burdens were created to assess accuracy and precision. Fifty bone scans were simulated with a tumor burden ranging from low to high disease confluence (0.10–13.0 BSI). A second group of 50 scans was divided into 5 subgroups, each containing 10 simulated bone scans, corresponding to BSI values of 0.5, 1.0, 3.0, 5.0, and 10.0. Repeat bone scan study: to assess the reproducibility in a routine clinical setting, 2 repeat bone scans were obtained from metastatic prostate cancer patients after a single 600-MBq 99mTc-methylene diphosphonate injection. Follow-up bone scan study: 2 follow-up bone scans of metastatic prostate cancer patients were analyzed to determine the interobserver variability between the automated BSIs and the visual interpretations in assessing changes. The automated BSI was generated using the upgraded EXINI boneBSI software (version 2). The results were evaluated using linear regression, Pearson correlation, Cohen κ measurement, coefficient of variation, and SD. Results Linearity of the automated BSI interpretations in the range of 0.10–13.0 was confirmed, and Pearson correlation was observed at 0.995 (n = 50; 95% confidence interval, 0.99–0.99; P cancer. PMID:26315832

  16. RHAMM (CD168 Is Overexpressed at the Protein Level and May Constitute an Immunogenic Antigen in Advanced Prostate Cancer Disease

    Directory of Open Access Journals (Sweden)

    Kilian M. Gust

    2009-09-01

    Full Text Available Localized prostate cancer (CaP can be cured using several strategies. However, the need to identify active substances in advanced tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human tumor antigen-targeted therapy, which is recognized by T cells or antibodies. We used data mining of the Cancer Immunome Database (CID, which comprises potential immunologic targets identified by serological screening of expression libraries. Candidate antigens were screened by DNA microarrays. Genes were then validated at the protein level by tissue microarrays, representing various stages of CaP disease. Of 43 targets identified by CID, 10 showed an overexpression on the complementary DNA array in CaP metastases. The RHAMM (CD168 gene, earlier identified by our group as an immunogenic antigen in acute and chronic leukemia, also showed highly significant overexpression in CaP metastases compared with localized disease and benign prostatic hyperplasia. At the protein level, RHAMM was highest in metastatic tissue samples and significantly higher in neoplastic localized disease compared with benign tissue. High RHAMM expression was associated with clinical parameters known to be linked to better clinical outcome. Patients with high RHAMM expression in the primaries had a significantly lower risk of biochemical failure. The number of viable cells in cell cultures was reduced in blocking experiments using hormone-sensitive and hormone-insensitive metastatic CaP cell lines. Acknowledging the proven immunogenic effects of RHAMM in leukemia, this antigen is intriguing as a therapeutic target in far-advanced CaP.

  17. 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.

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

    OpenAIRE

    Tilman Todenhöfer; Arnulf Stenzl; Hofbauer, Lorenz C.; Rachner, Tilman D.

    2015-01-01

    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 castrat...

  19. 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

  20. {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

  1. ONCOLOGICAL RESULTS OF RADICAL SURGICAL TREATMENT IN PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER

    OpenAIRE

    O. B. Loran; E. I. Veliyev; S. V. Kotov

    2014-01-01

    The authors consider and prove the efficiency of radical prostatectomy used in the treatment of patients with locally advanced prostate cancer as monotherapy and as a component of multimodality therapy.

  2. Determine of the optimal number of cycles of docetaxel in the treatment of metastatic castration-resistant prostate cancer.

    Science.gov (United States)

    Shen, Yuan-Chi; Chiang, Po-Hui; Luo, Hao-Lun; Chuang, Yao-Chi; Chen, Yen-Ta; Kang, Chih-Hsiung; Hsu, Chun-Chien; Lee, Wei-Ching; Cheng, Yuan-Tso

    2016-09-01

    To determine the optimal number of cycles of docetaxel for metastatic castration-resistant prostate cancer, we retrospectively collected 73 patients receiving varying numbers of docetaxel plus prednisolone and analyzed the clinical outcomes including overall survival, prostate-specific antigen (PSA) response, and adverse events. The study included 33 patients receiving ≤ 10 cycles of docetaxel and 40 patients receiving > 10 cycles. Patients receiving > 10 cycles were younger than those who received ≤ 10 cycles. There was no statistical significant difference in overall survival between the two groups (log-rank test, p = 0.75). Adverse effects were more common among patients receiving ≥ 10 cycles of treatment. A PSA flare-up was observed among six patients (8.2%); the median duration of the PSA surge was 3 weeks (range, 3-12 weeks). The overall survival rates in patients with PSA flare-up were comparable with the patients having PSA response. We concluded that at least four cycles of docetaxel should be administered in metastatic castration-resistant prostate cancer patients in order not to cease treatment prematurely from potentially beneficial chemotherapy. However, administering > 10 cycles does not result in any further improvement in survival and is associated with more adverse effects. PMID:27638405

  3. (-)-Oleocanthal as a c-Met inhibitor for the control of metastatic breast and prostate cancers.

    Science.gov (United States)

    Elnagar, Ahmed Y; Sylvester, Paul W; El Sayed, Khalid A

    2011-07-01

    The proto-oncogene receptor tyrosine kinase c-Met encodes the high-affinity receptor for hepatocyte growth factor (HGF). Dysregulation of the HGF-c-Met pathway plays a significant oncogenic role in many tumors. Overexpression of c-Met is a prognostic indicator for some transitional cell carcinomas. Extra-virgin olive oil (EVOO) provides a variety of minor phenolic compounds with beneficial properties. (-)-Oleocanthal (1) is a naturally occurring minor secoiridoid isolated from EVOO, which showed potent anti-inflammatory activity via its ability to inhibit COX-1 and COX-2. It altered the structure of neurotoxic proteins believed to contribute to the debilitating effects of Alzheimer's disease. Computer-Assisted Molecular Design (CAMD) identified 1 as a potential virtual c-Met inhibitor hit. Oleocanthal inhibited the proliferation, migration, and invasion of the epithelial human breast and prostate cancer cell lines MCF7, MDA-MB-231, and PC-3, respectively, with an IC (50) range of 10-20 µM, and demonstrated anti-angiogenic activity via downregulating the expression of the microvessel density marker CD31 in endothelial colony forming cells with an IC (50) of 4.4 µM. It inhibited the phosphorylation of c-Met kinase IN VITRO in the Z'-LYTE™ assay, with an IC (50) value of 4.8 µM. (-)-Oleocanthal and EVOO can have potential therapeutic use for the control of c-Met-dependent malignancies. PMID:21328179

  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. 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

  6. 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

    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...... while continuing androgen deprivation therapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints (rPFS, OS) were prospectively evaluated in nonvisceral and visceral subgroups. All other efficacy analyses were post hoc. RESULTS AND LIMITATIONS: Enzalutamide improved rPFS versus placebo...... significant benefits 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...

  7. The effectiveness of the TAX 327 nomogram in predicting overall survival in Chinese patients with metastatic castration-resistant prostate cancer

    OpenAIRE

    Bian, Xiao-Jie; Zhu, Yao; Shen, Yi-Jun; Wang, Jin-You; Ma, Chun-Guang; Zhang, Hai-Liang; Dai, Bo; Zhang, Shi-Lin; Yao, Xu-Dong; Ye, Ding-Wei

    2013-01-01

    Based on the results of TAX 327, a nomogram was developed to predict the overall survival of metastatic castration-resistant prostate cancer (mCRPC) after first-line chemotherapy. The nomogram, however, has not been validated in an independent dataset, especially in a series out of clinical trials. Thus, the objective of the current study was to validate the TAX 327 nomogram in a community setting in China. A total of 146 patients with mCRPC who received first-line chemotherapy (docetaxel or ...

  8. A Multicenter, Randomized Clinical Trial Comparing the Three-Weekly Docetaxel Regimen plus Prednisone versus Mitoxantone plus Prednisone for Chinese Patients with Metastatic Castration Refractory Prostate Cancer

    OpenAIRE

    Tie Zhou; Shu-xiong Zeng; Ding-wei Ye; Qiang Wei; Xu Zhang; Yi-ran Huang; Zhang-qun Ye; Yong Yang; , Wei Zhang; Ye Tian; Fang-jian Zhou; Jin Jie; Shi-ping Chen; Yan Sun; Li-ping Xie

    2015-01-01

    Purpose To explore the feasibility and efficacy of docetaxel plus prednisone for Chinese population with metastatic castration refractory prostate cancer (mCRPC). Patients and methods A total of 228 patients recruited from 15 centers were randomized to receive 10 cycles of D3P arm (docetaxel: 75 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily) or M3P arm (mitoxantrone: 12 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily). Pr...

  9. 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.

  10. Prognostic Value of Fluoro-D-glucose Uptake of Primary Tumor and Metastatic Lesions in Advanced Nonsmall Cell Lung Cancer

    OpenAIRE

    Nguyen, Xuan Canh; Nguyen, Khoi; Tran, Minh Thong; Maurea, Simone; Salvatore, Marco

    2014-01-01

    To assess the prognostic value of maximum standardized uptake value (maxSUV) of the primary tumor (maxSUVpt), maxSUV of whole-body tumors (maxSUVwb) and sum of maximum standardized uptake value (sumaxSUV) measured by the sum of maxSUVs of the primary tumor, metastatic lymph nodes, and metastatic lesions per each organ on fluoro-D-glucose-positron emission tomography/computed tomography in advanced non-small cell lung cancer (NSCLC). Eighty-three patients (49 male, 34 female) with advanced NSC...

  11. Progression to metastatic stage in a cellular model of prostate cancer is associated with methylation of the androgen receptor gene and transcriptional suppression of the insulin-like growth factor-I receptor gene

    OpenAIRE

    Schayek, Hagit; Bentov, Itay; Sun, Shihua; Plymate, Stephen R; Werner, Haim

    2010-01-01

    The progression of prostate cancer from an organ-confined, androgen-sensitive disease to a metastatic one is associated with dysregulation of androgen receptor (AR)-regulated target genes and with a decrease in insulin-like growth factor-I receptor (IGF1R) expression. DNA methylation of CpG islands is an epigenetic mechanism associated with gene silencing. Recent studies have demonstrated that methylation occurs early in prostate carcinogenesis and, furthermore, may contribute to androgen ind...

  12. 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...

  13. Outcome of Surgical Treatment for Metastatic Vertebra Bone Tumor in Advanced Lung Cancer

    Directory of Open Access Journals (Sweden)

    Akiko Fukuhara

    2010-03-01

    Full Text Available Background: Spinal metastases of patients with advanced stage lung cancer are an important target for palliative therapy, because their incidence is high, and they often cause severe symptoms and worsen the quality of life. Surgery is one of the most effective treatment options, but the indication of surgery is unclear as the procedure is invasive and patients with spinal metastasis have a rather short life expectancy. Furthermore, there have been few studies that have focused on lung cancer with poor prognosis. Methods: We reviewed all of the cases of lung cancer from January 1999 to July 2007 in the Department of Respiratory Medicine, Kyoto University Hospital, Japan. Thirteen patients with metastatic spinal tumor of lung cancer underwent surgery, and all of them had a poor performance status score (3 or 4. Results: Neurological improvement by at least 1 Frankel grade was seen in 10 of 14 cases (71%. Improvement of the movement capacity was noted in 9 of 14 cases (64%, and pain improvement was noted in 12 of 14 (86%. Median postoperative survival was 5 months (1–25 months. In particular, the group with a good postoperative performance status score (0–2 was shown to have a better median postoperative survival of 13 months. Conclusions: Surgical treatment for symptomatic metastatic spinal tumor of lung cancer can improve quality of life in a substantially high percentage of patients. Surgery should be considered even if preoperative performance status is poor.

  14. [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.

  15. 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.

  16. 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.

  17. Periostin is up-regulated in high grade and high stage prostate cancer

    International Nuclear Information System (INIS)

    Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far. Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n = 93) and a test cohort (n = 325). Metastatic prostate cancers (n = 20), hormone refractory prostate cancers (n = 19) and benign prostatic tissues (n = 38) were also analyzed. In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0%) of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%). Increased periostin expression in carcinoma cells was significantly associated with high Gleason score (p < 0.01) and advanced tumour stage (p < 0.05) in the test cohort. Whereas periostin expression was weak or absent in the stroma around normal prostate glands, strong periostin expression in tumour stroma was found in most primary and metastatic prostate cancers. High stromal periostin expression was associated with higher Gleason scores (p < 0.001). There was a relationship between stromal periostin expression and shortened PSA relapse free survival times in the training cohort (p < 0.05). Our data indicate that periostin up-regulation is related to increased tumour aggressiveness in prostate cancer and might be a promising target for therapeutical interventions in primary and metastatic prostate cancer

  18. Zoledronic acid in metastatic chondrosarcoma and advanced sacrum chordoma: two case reports

    Directory of Open Access Journals (Sweden)

    Capasso Elena

    2009-01-01

    Full Text Available Abstract Introduction Chondrosarcomas and chordomas are usually chemoresistant bone tumors and may have a poor prognosis when advanced. They are usually associated with worsening pain difficult to control. Patients and Methods Zoledronic acid was used in a 63-year-old man with metastatic chondrosarcoma and in a 66-year-old woman with a diagnosis of sacrum chordoma both reporting severe pain related to tumor. Results In the first case, zoledronic acid was able to maintain pain control despite disease progression following chemotherapy, in the other case, zoledronic acid only produced significant clinical benefit. Conclusion Control of pain associated with bone tumors such as chondrosarcoma and chondroma may significantly improve from use of zoledronic acid, independently from tumor response to other treatments. Evaluation on larger series are needed to confirm the clinical effect of this bisphosphonate on such tumors.

  19. Second-line therapy for gemcitabine-pretreated advanced or metastatic pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Romain Altwegg; Marc Ychou; Vanessa Guillaumon; Simon Thezenas; Pierre Senesse; Nicolas Flori; Thibault Mazard

    2012-01-01

    AIM:To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency,response,outcome,course of carbohydrate antigen 19-9 (CA 19-9)].METHODS:This retrospective study included all patients with advanced or metastatic pancreatic cancer (adenocarcinoma or carcinoma) treated with secondline chemotherapy in our center between 2000 and 2008.All patients received first-line chemotherapy with gemcitabine,and prior surgery or radiotherapy was permitted.We analyzed each chemotherapy protocol for second-line treatment,the number of cycles and the type of combination used.The primary endpoint was overall survival.Secondary endpoints included progression-free survival,response rate,grade 3-4 toxicity,dosage modifications and CA 19-9 course.RESULTS:A total of eighty patients (38%) underwent a second-line therapy among 206 patients who had initially received first-line treatment with a gemcitabine-based regimen.Median number of cycles was 4 (range:1-12) and the median duration of treatment was 2.6 mo (range:0.3-7.4).The overall disease control rate was 40.0%.The median overall survival and progression-free survival from the start of second-line therapy were 5.8 (95% CI:4.1-6.6) and 3.4 mo (95% CI:2.4-4.2),respectively.Toxicity was generally acceptable.Median overall survival of patients with a CA 19-9 level declining by more than 20% was 10.3 mo (95% CI:4.5-11.6) vs 5.2 mo (95% CI:4.0-6.4) for others (P =0.008).CONCLUSION:A large proportion of patients could benefit from second-line therapy,and CA 19-9 allows efficient treatment monitoring both in first and secondline chemotherapy.

  20. 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.

  1. Grappling with the androgen receptor—a new approach for treating advanced prostate cancer

    OpenAIRE

    Thompson, Timothy C.

    2010-01-01

    In this issue of Cancer Cell, Andersen et al report on a small molecule that interacts with and blocks transactivation of the androgen receptor amino-terminal domain. This agent can overcome the shortcomings of clinically used antiandrogens, an important advance in the development of effective therapy for advanced prostate cancer.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. A COMPARATIVE STUDY OF PROSTATIC SPECIFIC ANTIGEN DENSITY AND ITS CORRELATED HISTOPATHOLOGY IN THE DIAGNOSIS OF BENIGN AND MALIGNANT PROSTATIC DISEASES

    Directory of Open Access Journals (Sweden)

    Shravan R

    2015-07-01

    Full Text Available BACKGROUND : Carcinoma of prostate gland is the most common malignancy above 65 yrs of age in men. Most patients with early - stage Ca prostate are asymptomatic. The presence of symptoms often suggests locally advanced or metastatic disease. It is important to detect Ca prostate at an early stage so that mortality due to this malignancy can be minimized. The specific threshold for prostate - specific antigen (PSA to delineate patients who are at the highest risk has been controversial. It is wiser to refine PSA by its derivative parameter like PSAD (PSA/Vol . which can be used as a better diagnostic tool in early detection of Ca Prostate.

  9. Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial

    DEFF Research Database (Denmark)

    Kwon, Eugene D; Drake, Charles G; Scher, Howard I;

    2014-01-01

    BACKGROUND: Ipilimumab is a fully human monoclonal antibody that binds cytotoxic T-lymphocyte antigen 4 to enhance antitumour immunity. Our aim was to assess the use of ipilimumab after radiotherapy in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel c...... that warrant further investigation. FUNDING: Bristol-Myers Squibb....

  10. Androgen Control in Prostate Cancer.

    Science.gov (United States)

    Pelekanou, Vasiliki; Castanas, Elias

    2016-10-01

    Research on prostate cancer has extensively advanced in the past decade, through an improved understanding for its genetic basis and risk-stratification. Molecular classification of prostate cancer into distinct subtypes and the recognition of new histologic entities promise the development of tailored-made management strategies of patients. Nowadays, various alternatives are available for clinical management of localized disease ranging from observation alone through radical prostatectomy. In patients with castration-resistant prostate cancer, the approval of new drugs for the management of metastatic disease has offered promising results improving the survival of these patients. In this context, androgen receptors (AR) remain at the epicenter of prostate cancer research holding a prominent role in the biology and therapeutic regimens of prostate cancer. As many of castration-resistant tumors retain hormone-responsiveness, AR is a clinical relevant, druggable target. However, AR paradoxically remains neglected as a prostate cancer biomarker. The great advancements in prostate cancer preclinical and clinical research, imply further improvement in clinical and translational data, for patient selection and treatment optimization. For a precision medicine-guided clinical management of prostate cancer, AR evaluation has to be implemented in companion and complementary diagnostics, as discussed here. J. Cell. Biochem. 117: 2224-2234, 2016. © 2016 Wiley Periodicals, Inc. PMID:27104784

  11. 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...

  12. Prostate cancer immunotherapy: beyond immunity to curability.

    Science.gov (United States)

    Simons, Jonathan W

    2014-11-01

    Metastatic prostate cancer is the second leading cause of death from cancer in the United States. It is the first prevalent cancer in which overall survival in advanced disease is modestly, but objectively, improved with outpatient delivered dendritic cell-based immunotherapy. More prostate cancer patients have enrolled through Facebook and trusted-site Internet searches in clinical trials for prostate cancer vaccine-based immunotherapy than in immunotherapy trials for lung, breast, colon, pancreas, ovarian, and bladder cancer combined in the past 7 years. Exceptional responses to anti-CTLA-4 treatment have been documented in clinics, and prostate cancer neoantigen characterization and T-cell clonotyping are in their research ascendancy. The prostate is an accessory organ; it is not required for fertility, erectile function, or urinary continence. The true evolutionary advantage of having a prostate for male mammalian physiology is a topic of speculation in seminar rooms and on bar stools, but it remains unknown. Hundreds of prostate lineage-unique proteins (PLUP) exist among the >37,000 normal human prostate lineage-unique open reading frames that can be targeted for immunologic ablation of PLUP(+) prostate cancer cells by prostate-specific autoimmunity. This bioengineered graft-versus-prostate disease is a powerful strategy that can eliminate deaths from prostate cancer. Immunologic tolerance to prostate cancer can be overcome at every clinical stage of presentation. This Cancer Immunology at the Crossroads article aims to present advances in the past two decades of basic, translational, and clinical research in prostate cancer, including bioengineering B-cell and T-cell responses, and ongoing prostate cancer immunotherapy trials. PMID:25367978

  13. 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

    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...... 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...

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

    OpenAIRE

    L. V. Shaplygin; V. A. Solovov; M. O. Vozdvizhenskiy; Yа. S. Matyash; R. Z. Khametov; D. V. Fesenko

    2014-01-01

    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 %, respectivel...

  15. 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. 

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

    Directory of Open Access Journals (Sweden)

    L. V. Shaplygin

    2014-07-01

    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. 

  17. 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...

  18. New perspectives in the treatment of advanced or metastatic gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Gerardo Rosati; Domenica Ferrara; Luigi Manzione

    2009-01-01

    Metastatic gastric cancer remains an incurable disease,with a relative 5-year survival rate of 7%-27%.Chemotherapy,which improves overall survival (OS) and quality of life,is the main treatment option.Metaanalysis has demonstrated that the best survival results obtained in earlier randomized studies were achieved with three-drug regimens containing a fluoropyrimidine,an anthracycline,and cisplatin (ECF).Although there has been little progress in improving median OS times beyond the 9-mo plateau achievable with the standard regimens,the availability of newer agents has provided some measure of optimism.A number of new combinations incorporating docetaxel,oxaliplatin,capecitabine,and S-1 have been explored in randomized trials.Some combinations,such as epirubicin-oxaliplatincapecitabine,have been shown to be as effective as (or perhaps more effective than) ECF,and promising early data have been derived for S-1 in combination with cisplatin.One factor that might contribute to extending median OS is the advancement whenever possible to second-line cytotoxic treatments.However,the biggest hope for significant survival advances in the near future would be the combination of new targeted biological agents with existing chemotherapy first-line regimens.

  19. On the development of models in mice of advanced visceral metastatic disease for anti-cancer drug testing.

    Science.gov (United States)

    Man, Shan; Munoz, Raquel; Kerbel, Robert S

    2007-12-01

    It is well known clinically that advanced, bulky visceral metastatic disease is generally much less responsive to most anti-cancer therapies, compared to microscopic metastatic disease. This problem is exacerbated when treating cancers that have been previously exposed to multiple lines of therapy, and which have acquired a 'refractory' phenotype. However, mimicking such clinical treatment situations in preclinical mouse models involving the testing of new or existing cancer therapies is extremely rare. Treatment of 'metastasis', in retrospect, usually involves minimal residual disease and therapy naïve tumors. This could account in many instances for the failure to reproduce highly encouraging preclinical results in subsequent phase I or phase II clinical trials. To that end, we have embarked on an experimental program designed to develop models of advanced, visceral metastatic disease, in some cases involving tumors previously exposed to various therapies. The strategy first involves the orthotopic transplantation of a human cancer cell line, such as breast cancer cell line, into the mammary fat pads of immune deficient mice, followed by surgical resection of the resultant primary tumors that develops. Recovery of distant macroscopic metastases, usually in the lungs, is then undertaken, which can take up to 4 months to visibly form. Cell lines are established from such metastases and the process of orthotopic transplantation, surgical resection, and recovery of distant metastases is undertaken, at least one more time. Using such an approach highly metastatically aggressive variant sublines can be obtained, provided they are once again injected into an orthotopic site and the primary tumors removed by surgery. By waiting sufficient time after removal of the primary tumors, about only 1 month, mice with extensive metastatic disease in sites such as the lungs, liver, and lymph nodes can be obtained. An example of therapy being initiated in an advanced stage of such

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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......-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...... = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change...

  5. Serum testosterone suppression and potential for agonistic stimulation during chronic treatment with monthly depot formulation of domestic substitute of leuprorelin acetate microspheres for metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    Dongliang Pan; Liming Dong; Lianchao Jin; Bing Yang; Zhe Zhou; Kai Zhang; Xianghua Zhang; Ningchen Li

    2014-01-01

    We aimed to evaluate the eficiency of serum testosterone suppression as wel as the potential for agonistic stimulation of serum testosterone during chronic treatment with monthly (3.75 mg) depot formulation of domestic substitute of leuprorelin acetate microspheres for patients with metastatic prostate cancer.Methods: A total of 23 patients with metastatic prostate cancer were enroled in the prospective study and received 6 monthly intramuscular depot injections of domestic substitute of leuprorelin acetate microspheres. Their levels and patterns of serum testosterone suppression and the potential for agonistic stimulation of serum testosterone were monitored folowing injection monthly (3.75 mg) depot formula-tion of domestic substitute of leuprorelin acetate microspheres for 24 weeks.Results: Mean testosterone was 431.4 ng/dL, 119.3 ng/dL, 28.2 ng/dL by week 1, 2, 3 and decreased to less than 15.6 ng/dL by week 4 where it remained throughout the treatment period. Median time to suppression of serum testosterone was 20.7 days. No transient minor “escape” from sup-pression occurred in al patients which was defined as a single testosterone value greater than 50 ng/dL once suppression was achieved. Assessment of agonistic stimulation folowing the second depot injection revealed no pattern of stimulation. Conclusion: We concluded that monthly (3.75 mg) depot formulation of domestic substitute of leuprorelin acetate micro-spheres could provide persistent, stable suppression of serum testosterone throughout the dosing intervals, and that the initial depot injection of this formulation also could provide suficient pituitary desensitization to prevent agnostic stimulation of serum testosterone during chronic treatment.

  6. Clamp ablation of the testes compared to bilateral orchiectomy as androgen deprivation therapy for advanced prostate cancer

    Directory of Open Access Journals (Sweden)

    AD Zarrabi

    2011-06-01

    Full Text Available PURPOSE: Burdizzo clamp ablation of the testes (CAT may provide an incisionless, cost-effective form of androgen deprivation therapy (ADT in men with adenocarcinoma of the prostate (ACP who find bilateral orchiectomy (BO unacceptable or can not afford medical ADT. The aim of this study was to compare CAT with BO as primary ADT in men with ACP. MATERIALS AND METHODS: Written, informed consent was obtained from men with locally advanced or metastatic ACP. Patients were prospectively randomized to BO (n = 9 or CAT (n = 10 under local anaesthesia, and were evaluated 3 and 7 days, 6 weeks and 3 months post-procedure. The protocol was approved by the local institutional ethics committee. Statistical analysis was performed using Student's, Mann-Whitney's and Fisher's tests. RESULTS: Mean duration of the procedure was significantly longer for BO than CAT (16.9 vs. 10.9 minutes. Mean pain scores during and after the procedure did not differ significantly. Serum testosterone decreased significantly on days 3 and 7 after CAT, but increased at 6 weeks, and was significantly higher than after BO. Serum luteinizing hormone increased significantly from day 3 after BO and from day 7 after CAT. Serum prostate specific antigen decreased significantly after BO, but not after CAT. Minor complications were more common after BO (89% than CAT (40%. In the 9 men who did not achieve castrate levels of testosterone after CAT, BO was performed. CONCLUSIONS: CAT was quicker to perform and had a lower complication rate, but was not as effective as BO in achieving castrate serum testosterone levels.

  7. 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

  8. Recent advances in prostate cancer pathology: Gleason grading and beyond.

    Science.gov (United States)

    Shah, Rajal B; Zhou, Ming

    2016-05-01

    Since its initial description in 1966 by Dr Donald Gleason, Gleason grading has become the cornerstone in the management of prostate cancer (PCa). With widespread use of Prostate Specific Antigen (PSA) screening and needle core biopsy, the diagnosis and management of PCa have dramatically evolved. In addition, better understanding of the morphological spectrum of prostate cancer and its clinical significance have prompted the refinement of the grading criteria and reporting guidelines commensurate to contemporary practice. The modification of the Gleason grading system implemented by the International Society of Urological Pathology in 2005 and subsequent revision in 2014 has profoundly impacted how PCa is graded and managed. This review aims to provide a concise update on the refinement of the histological criteria for various Gleason patterns and problem areas of Gleason grading, and provide recommendations on how to improve the grading reproducibility. The new proposal to group Gleason scores into clinically meaningful "grade groups" will also be discussed. Finally, we will discuss how magnetic resonance imaging (MRI)-targeted biopsy and emerging genetic markers may help improve the Gleason grading accuracy and risk stratification currently based on clinicopathological parameters. PMID:26991008

  9. 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

  10. 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)

  11. 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

  12. Palliation of malignant rectal obstruction from invasive prostate cancer with multiple overlapping self-expanding metal stents.

    Science.gov (United States)

    Smith, Aja S; Cole, Matthew; Vega, Kenneth J; Munoz, Juan Carlos

    2009-12-01

    Self-expandable metal stents (SEMS) are used for colonic neoplastic and extracolonic metastatic obstruction relief. Limited data exists on their use for locally invasive prostate cancer. We describe a unique approach using overlapping SEMS to alleviate a rectosigmoid obstruction from locally invasive prostate cancer. A patient with locally advanced prostate cancer presented with obstipation and lymphedema. Placement of overlapping rectosigmoid SEMS was performed, relieving the visualized rectosigmoid obstruction. PMID:20016435

  13. 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 .

  14. 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

    Science.gov (United States)

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

    2016-01-01

    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 October 2014 for radium-223 therapy. We faced the following dilemma: is radium-223 standard therapy? Is it cost-effective? Medline was searched employing the following search criteria: “radium-223”, “alpharadin”, “Xofigo” and “prostate”. Exclusion and inclusion criteria were applied. Guidelines and cost-effectiveness analyses were focused. We also searched the websites of ASCO, ESMO and ISPOR. The web was searched, using Yahoo and Google search engines, for Health Technology Assessments (HTAs). Results: 181 publications were identified in the Medline database. Only four studies included the word “cost”, three “economics” and none “budget” in heading or abstract. None of the publications were thorough of cost analysis (cost-effectiveness, cost-utility, cost-minimizing or cost-of-illness analysis). Six HTAs and eight national guidelines were identified. The cost per quality adjusted life years was indicated €80.000-94,000. HTAs concluded reimbursement being not recommendable or no ultimate statement could be made. One pointed towards a limited use with caution. Conclusion: Guidelines were based on data from randomized clinical trials (RCTs). Health economics was not considered when guidelines were made. Most HTAs concluded this therapy not cost-effective or there was insufficient data for final conclusions. Licensing and reimbursement processes should be run simultaneously. PMID:26573043

  15. 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...

  16. 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; von der Maase, H; Sengeløv, L;

    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 data from a large....... These results strengthen the role of GC as a standard of care in patients with locally advanced and metastatic transitional-cell carcinoma (TCC)....

  17. Highly efficacious nontoxic preclinical treatment for advanced metastatic breast cancer using combination oral UFT-cyclophosphamide metronomic chemotherapy.

    Science.gov (United States)

    Munoz, Raquel; Man, Shan; Shaked, Yuval; Lee, Christina R; Wong, John; Francia, Giulio; Kerbel, Robert S

    2006-04-01

    Metronomic antiangiogenic chemotherapy, the prolonged administration of relatively low drug doses, at close regular intervals with no significant breaks, has been mainly studied at the preclinical level using single chemotherapeutic drugs, frequently in combination with a targeted antiangiogenic drug, and almost always evaluated on primary localized tumors. We tested a "doublet" combination metronomic chemotherapy treatment using two oral drugs, UFT, a 5-fluorouracil (5-FU) prodrug administered by gavage, and cyclophosphamide, for efficacy and toxicity in a new mouse model of advanced, terminal, metastatic human breast cancer. The optimal biological dose of each drug was first determined by effects on levels of circulating endothelial progenitor cells as a surrogate marker for angiogenesis, which was assessed to be 15 mg/kg for UFT and 20 mg/kg for cyclophosphamide. A combination treatment was then evaluated in mice with advanced metastatic disease using a serially selected metastatic variant of the MDA-MB-231 breast cancer-cell line, 231/LM2-4. UFT or cyclophosphamide treatment showed only very modest survival advantages whereas a combination of the two resulted in a remarkable prolongation of survival, with no evidence of overt toxicity despite 140 days of continuous therapy, such that a significant proportion of mice survived for over a year. In contrast, this striking therapeutic effect of the combination treatment was not observed when tested on primary orthotopic tumors. We conclude that combination oral low-dose daily metronomic chemotherapy, using cyclophosphamide and UFT, is superior to monotherapy and seems to be a safe and highly effective experimental antimetastatic therapy, in this case, for advanced metastatic breast cancer.

  18. Managing locally advanced prostate cancer: a urologist's and a patient's perspective.

    Science.gov (United States)

    Kirby, Roger; Offen, Nigel

    2006-03-01

    A 60-year-old man presented to his general practitioner with prostatic symptoms and high blood pressure. Based upon a prostate-specific antigen level of 44 ng/ml and further investigations (digital rectal examination, transrectal ultrasound-guided needle biopsy, and magnetic resonance imaging, ultrasound and bone scans), the patient was diagnosed with locally advanced (cT3, N0, M0) prostate cancer. Here, the urologist and the patient describe treatment from their respective viewpoints. Following discussion of the advantages and disadvantages of the various therapeutic options, radiotherapy plus hormonal therapy (bicalutamide 150 mg) was chosen as the approach that best suited the patient's lifestyle. In this review, the patient and the urologist consider the impact of the chosen treatment in terms of efficacy, tolerability and quality of life. PMID:16520652

  19. 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。

  20. 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....

  1. 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

    International Nuclear Information System (INIS)

    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

  2. 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.

  3. PREVENTION OF COMPLICATIONS IN CASTRATE-REFRACTORY PROSTATE CANCER PATIENTS WITH BONE METASTASES

    Directory of Open Access Journals (Sweden)

    K. M. Nushko

    2015-01-01

    Full Text Available Abstract:Prostate cancer (PC is one of the most urgent problems in modern oncourology. Every year the world is recording more than 900 thousands new cases of prostate cancer. For this reason, the diagnosis and treatment of this disease has recently been given more attention, both abroad and in the Russian Federation. Despite improvements in diagnostic methods and implementation of programs for active detection of the disease in its early stages, the number of patients suffering from advanced forms of prostate cancer remains high. Currently, the main method of treatment in patients with metastatic prostate cancer remains the hormone therapy (HT. Patients with metastatic prostate cancer most frequently have localization of metastatic lesions in the lymph nodes and bones. Frequent localization of metastatic lesions in the bones is due to tumor cell tropism of prostate cancer to the bone. Metastatic bone disease, as well as long-term HT conducted in patients with metastatic prostate cancer, leads to irreversible disruption of bone remodeling, which may be accompanied by osteoporosis and fragility fractures. Bone metastases in patients with PC are the most common cause of complications and significantly impair the quality of life of patients. Therapy underlying the prevention of bone complications can be specific, aimed directly at the tumor tissue and non-specific, to strengthen bones and decrease its resorption processes. The article provides an overview of the literature covering the effectiveness of modern drugs, aimed at non-specific prevention of bone complications in patients with metastatic prostate cancer, such as bisphosphonates, and inhibitors of the ligand RANKL, as well as an overview of studies to assess the effectiveness of domestic analogue zolendronovoy acid preparation Resorba in the prevention of osteoporosis.

  4. 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.

  5. Volume of Bone Metastasis Assessed with Whole-Body Diffusion-weighted Imaging Is Associated with Overall Survival in Metastatic Castration-resistant Prostate Cancer.

    Science.gov (United States)

    Perez-Lopez, Raquel; Lorente, David; Blackledge, Matthew D; Collins, David J; Mateo, Joaquin; Bianchini, Diletta; Omlin, Aurelius; Zivi, Andrea; Leach, Martin O; de Bono, Johann S; Koh, Dow-Mu; Tunariu, Nina

    2016-07-01

    Purpose To determine the correlation between the volume of bone metastasis as assessed with diffusion-weighted (DW) imaging and established prognostic factors in metastatic castration-resistant prostate cancer (mCRPC) and the association with overall survival (OS). Materials and Methods This retrospective study was approved by the institutional review board; informed consent was obtained from all patients. The authors analyzed whole-body DW images obtained between June 2010 and February 2013 in 53 patients with mCRPC at the time of starting a new line of anticancer therapy. Bone metastases were identified and delineated on whole-body DW images in 43 eligible patients. Total tumor diffusion volume (tDV) was correlated with the bone scan index (BSI) and other prognostic factors by using the Pearson correlation coefficient (r). Survival analysis was performed with Kaplan-Meier analysis and Cox regression. Results The median tDV was 503.1 mL (range, 5.6-2242 mL), and the median OS was 12.9 months (95% confidence interval [CI]: 8.7, 16.1 months). There was a significant correlation between tDV and established prognostic factors, including hemoglobin level (r = -0.521, P < .001), prostate-specific antigen level (r = 0.556, P < .001), lactate dehydrogenase level (r = 0.534, P < .001), alkaline phosphatase level (r = 0.572, P < .001), circulating tumor cell count (r = 0.613, P = .004), and BSI (r = 0.565, P = .001). A higher tDV also showed a significant association with poorer OS (hazard ratio, 1.74; 95% CI: 1.02, 2.96; P = .035). Conclusion Metastatic bone disease from mCRPC can be evaluated and quantified with whole-body DW imaging. Whole-body DW imaging-generated tDV showed correlation with established prognostic biomarkers and is associated with OS in mCRPC. (©) RSNA, 2016 Online supplemental material is available for this article. PMID:26807894

  6. Neoadjuvant androgen withdrawal prior to external radiotherapy for locally advanced adenocarcinoma of the prostate

    International Nuclear Information System (INIS)

    It is unclear whether positive interactions between radiation and androgen withdrawal for patients with locally advanced prostate cancer is synergistic or additive. The present study aimed to clarify the significance of neoadjuvant androgen ablation prior to external radiotherapy in a human prostate LNCaP tumor model and in patients with locally advanced prostate cancer. Comparisons were made between the effect of castration prior to radiation on the growth of subcutaneous LNCaP tumors implanted into male nude mice and their serum prostate-specific antigen (PSA) levels, and the results of castration or radiation alone. Twenty-nine patients with histologically proven and locally advanced adenocarcinoma of the prostate were treated with luteinizing hormone-releasing hormone analog at least 3 months before, during, and after external radiation therapy with a total dose of 70 Gy. The toxicity and response to this therapy were evaluated. Treatment combining castration and radiation resulted in synergistic inhibition of LNCaP tumor growth and a significant delay in the emergence of androgen-independent recurrence as opposed to either treatment alone. The external radiotherapy was completed in 28 patients (96.6%), resulting in a reduction of serum PSA levels in all 28 patients to below 1.0 ng/mL. All patients were alive after a mean follow-up period of 34 months (range 11-53) with a 3-year PSA relapse-free survival rate of 83.7%. Among several factors examined, only the Gleason score was significantly associated with PSA relapse-free survival in univariate analysis, but not in multivariate analysis. Thirteen of 28 patients (46%) and 7 of 28 (25%) also showed at least one form of gastrointestinal or genitourinary toxicity, respectively. Of these patients, 8 with gastrointestinal toxicities, and 1 with genitourinary toxicity, experienced acute complications higher than grade 3. The experimental findings objectively suggested the use of neoadjuvant androgen withdrawal prior

  7. 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.

  8. Design and preclinical evaluation of a 99mTc-labelled diabody of mAb J591 for SPECT imaging of prostate-specific membrane antigen (PSMA)

    OpenAIRE

    Kampmeier, Florian; Williams, Jennifer D.; Maher, John; Mullen, Gregory E.; Blower, Philip J.

    2014-01-01

    Background Sensitive and specific detection of nodal status, sites of metastases and low-volume recurrent disease could greatly improve management of patients with advanced prostate cancer. Prostate-specific membrane antigen (PSMA) is a well-established marker for prostate carcinoma with increased levels of expression in high-grade, hormone-refractory and metastatic disease. The monoclonal antibody (mAb) J591 is directed against an extracellular epitope of PSMA and has been shown to efficient...

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

    Science.gov (United States)

    Hao, Yanni; Wolfram, Verena; Cook, Jennifer

    2016-01-01

    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, income, and education, as well as disease progression, choice of utility elicitation method, and country settings, were identified

  10. Common Genetic Variation in CYP17A1 and Response to Abiraterone Acetate in Patients with Metastatic Castration-Resistant Prostate Cancer.

    Science.gov (United States)

    Binder, Moritz; Zhang, Ben Y; Hillman, David W; Kohli, Rhea; Kohli, Tanvi; Lee, Adam; Kohli, Manish

    2016-01-01

    Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P. Logistic regression was used to assess the association between tag SNPs and biochemical response. Proportional hazards regression was used to assess the association between tag SNPs and time to biochemical progression. Odds or hazard ratio per minor allele were estimated and p-values below 0.05 were considered statistically significant. Germline DNA was successfully genotyped for four tag SNPs in 87 patients. The median age was 73 years (54-90); the median prostate-specific antigen was 66 ng/dL (0.1-99.9). A single SNP, rs2486758, was associated with lower odds of experiencing a biochemical response (Odds ratio 0.22, 95% confidence interval 0.07-0.63, p = 0.005) and a shorter time to biochemical progression (Hazard ratio 2.23, 95% confidence interval 1.39-3.56, p < 0.001). This tag SNP located in the promoter region of CYP17A1 will need further validation as a predictive biomarker for AA/P therapy. PMID:27409606

  11. Treatment evolution for metastatic castration-resistant prostate cancer with recent introduction of novel agents: retrospective analysis of real-world data.

    Science.gov (United States)

    Flaig, Thomas W; Potluri, Ravi C; Ng, Yvette; Todd, Mary B; Mehra, Maneesha

    2016-02-01

    Despite increasing drug treatment options for metastatic castration-resistant prostate cancer (mCRPC) patients, real-world treatment data are lacking. We conducted retrospective analyses of commercial claims and electronic medical record (EMR) databases to understand how treatment patterns for mCRPC have changed in a US-based real-world population. Truven Health Analytics MarketScan(®) (2000-2013) and EMR (2004-2013) databases were used to identify patients with an index prostate cancer diagnosis (ICD-9 codes 185X or 233.4X) and prescription claims for an mCRPC drug (mitoxantrone, estramustine, docetaxel, sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, or radium-223). Regimen analyses for first line of therapy (LOT1), second line of therapy, and beyond were performed among cohorts based on year of first mCRPC drug usage. mCRPC drug usage and treatment duration were compared across cohorts and age groups within each cohort. The commercial claims cohort yielded 3437 evaluable patients. Most men (91%) commencing mCRPC treatment had docetaxel as LOT1 in 2010; this number had declined to 15% in 2013. In 2013, 67% and 9% of patients used abiraterone acetate and enzalutamide, respectively, as LOT1. Among both commercial claims and EMR cohorts, treatment pattern changes were most pronounced in men aged >80 years, and median treatment duration for some mCRPC drugs was shorter than expected based on available clinical trial information. These results demonstrate a shift in mCRPC treatments during the past 5 years, with greater use of newer noncytotoxic treatments than docetaxel. These real-world data aid in understanding the changing role of chemotherapy in the management of mCRPC.

  12. Advances in prostate cancer chemoprevention: a translational perspective.

    Science.gov (United States)

    Nambiar, Dhanya; Singh, Rana P

    2013-01-01

    Chemopreventive interventions are steadily emerging as an important aspect of cancer management and control. Herein, we have discussed the major epidemiological and clinical studies advocating the role of androgen inhibitors, flavonoids and antioxidants in preventing prostate cancer (PCa). Androgen inhibitors have lately been discussed not only in treatment of PCa, but also as preventive agents especially after trials with Finasteride and Dutasteride. Flavonoids such as silibinin, green tea polyphenols, genistein, curcumin have shown great promise, but avenues to improve their bioavailability are requisite. Agents with antioxidant potentials like lycopene, selenium, and vitamin E have also been explored. Antioxidant trials have yielded mixed results or benefitted only a subgroup of population, although further studies are needed to establish them as preventive agent. Although a majority of the trials resulted in positive outcomes supporting their role as preventive agents; one should be cautious of neutral or negative results as well. For clinical applicability of these agents, we need to identify the ideal target population, time of intervention, appropriate dosage, and extent of intervention required. Incoherency of data with these agents urges for a stringent study design and thorough interpretation to accurately judge the necessity and feasibility of the preventive measures. PMID:23682779

  13. Randomised, phase II trial comparing oral capecitabine (Xeloda®) with paclitaxel in patients with metastatic/advanced breast cancer pretreated with anthracyclines

    OpenAIRE

    Talbot, D C; Moiseyenko, V; Van Belle, S; O'Reilly, S. M.; Alba Conejo, E; Ackland, S; Eisenberg, P; Melnychuk, D.; Pienkowski, T; Burger, H-U; Laws, S.; Osterwalder, B

    2002-01-01

    Capecitabine, an oral fluoropyrimidine carbamate, was designed to generate 5-fluorouracil preferentially at the tumour site. This randomised, phase II trial evaluated the efficacy and safety of capecitabine or paclitaxel in patients with anthracycline-pretreated metastatic breast cancer. Outpatients with locally advanced and/or metastatic breast cancer whose disease was unresponsive or resistant to anthracycline therapy were randomised to 3-week cycles of intermittent oral capecitabine (1255 ...

  14. 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.

  15. 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.

  16. 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.

  17. Advancements in the Treatment of Metastatic Breast Cancer (MBC: The Role of Ixabepilone

    Directory of Open Access Journals (Sweden)

    Massimo Cristofanilli

    2012-01-01

    Full Text Available Successful management of breast cancer in the metastatic setting is often confounded by resistance to chemotherapeutics, in particular anthracyclines and taxanes. The limited number of effective treatment options for patients with more aggressive biological subtypes, such as triple-negative metastatic breast cancer, is especially concerning. As such, a therapy clinically proven to be effective in this subtype would be of great value. Ixabepilone, a novel synthetic lactam analog of epothilone B, demonstrated better clinical outcomes in metastatic disease, particularly in triple-negative breast cancer. Most recently, studies have shown the activity of ixabepilone in the neoadjuvant setting, suggesting a role for this drug in primary disease. Notably, treating in the neoadjuvant setting might allow clinicians to explore the predictive value of biomarkers and response to treatment, as pharmacogenomic approaches to therapy continue to evolve. In this article, we review the efficacy and safety data of ixabepilone as a monotherapy and as a component of combination therapy for metastatic and primary breast cancer.

  18. 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.

  19. 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.

  20. 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....

  1. 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

  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 < 0.002; for D9902B, adjusted HR 0.78 (95 % CI 0.61, 0.98) p = 0.03. There was no significant difference between groups in D9902A, unadjusted HR 0.79 (95 % CI 0.48, 1.28) p = 0.331. 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

  3. 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 ...

  4. Veliparib, Capecitabine, and Temozolomide in Patients With Advanced, Metastatic, and Recurrent Neuroendocrine Tumor

    Science.gov (United States)

    2016-07-10

    Functional Pancreatic Neuroendocrine Tumor; Malignant Somatostatinoma; Merkel Cell Carcinoma; Metastatic Adrenal Gland Pheochromocytoma; Metastatic Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Multiple Endocrine Neoplasia Type 2A; Multiple Endocrine Neoplasia Type 2B; Neuroendocrine Neoplasm; Non-Functional Pancreatic Neuroendocrine Tumor; Pancreatic Glucagonoma; Pancreatic Insulinoma; Recurrent Adrenal Cortex Carcinoma; Recurrent Adrenal Gland Pheochromocytoma; Recurrent Merkel Cell Carcinoma; Somatostatin-Producing Neuroendocrine Tumor; Stage III Adrenal Cortex Carcinoma; Stage III Thyroid Gland Medullary Carcinoma; Stage IIIA Merkel Cell Carcinoma; Stage IIIB Merkel Cell Carcinoma; Stage IV Adrenal Cortex Carcinoma; Stage IV Merkel Cell Carcinoma; Stage IVA Thyroid Gland Medullary Carcinoma; Stage IVB Thyroid Gland Medullary Carcinoma; Stage IVC Thyroid Gland Medullary Carcinoma; Thymic Carcinoid Tumor; VIP-Producing Neuroendocrine Tumor; Well Differentiated Adrenal Cortex Carcinoma; Zollinger Ellison Syndrome

  5. Improved clinical response to Sr-89 with increasing dose in patients with metastatic prostate and breast cancer in bone

    International Nuclear Information System (INIS)

    The authors have investigated a possible dose-response effect with increasing therapeutic doses of Sr- 89. Thirty-two patients with painful metastatic skeletal deposits completed a phase I-II standard 3-month protocol. Sr-89 administered doses ranged from 25 to 85 μCi/kg body weight. Clinical response was graded on a five-point scale. The mean level of clinical response was calculated for each dose range. The mean response rating for 25 μCi/kg was 2.33; 40 μCi/kg, 3.55; 55 μCi/kg, 3.70; 70 μCi/kg, 4.60; and 85 μCi/kg, 4.00. Probit analysis demonstrated a highly significant dose-response curve. No patients exhibited unacceptable hematologic toxicity. Sr-89 administration at higher dose levels provides improved clinical response with acceptable hematologic toxicity

  6. 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.

  7. 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....

  8. A comprehensive bone-health management approach for men with prostate cancer receiving androgen deprivation therapy

    OpenAIRE

    Lee, C. E.; Leslie, W.D.; Czaykowski, P.; Gingerich, J.; Geirnaert, M.; Lau, Y.K.J.

    2011-01-01

    For advanced and metastatic prostate cancer, androgen deprivation therapy (adt) is the mainstay of treatment. Awareness of the potential bone-health complications consequent to adt use is increasing. Many studies have shown that prolonged adt leads to significant bone loss and increased fracture risk that negatively affect quality of life. Clinical practice guidelines for preserving bone health in men with prostate cancer on adt vary across Canada. This paper reviews recent studies on bone he...

  9. Vimentin and Ki67 expression in circulating tumour cells derived from castrate-resistant prostate cancer

    OpenAIRE

    Lindsay, C. R.; Le Moulec, S.; Billiot, F.; Loriot, Y; Ngo-Camus, M.; Vielh, P; Fizazi, K; Massard, C; Farace, F.

    2016-01-01

    Background High circulating tumor cell (CTC) counts are associated with poor prognosis in advanced prostate cancer, and recently CTC number was suggested to be a surrogate for survival in metastatic castrate-resistant prostate cancer (mCRPC). Ki67 and vimentin are well-characterised markers of tumour cell proliferation and the epithelial-mesenchymal transition (EMT), respectively. Here we asked if the expression of vimentin and Ki67 in CTCs offered prognostic or predictive information in mCRP...

  10. 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

  11. PET/CT Imaging and Radioimmunotherapy of Prostate Cancer

    DEFF Research Database (Denmark)

    Bouchelouche, Kirsten; Tagawa, Scott T; Goldsmith, Stanley J;

    2011-01-01

    of more effective treatment modalities that could improve outcome. Prostate cancer represents an attractive target for radioimmunotherapy (RIT) for several reasons, including pattern of metastatic spread (lymph nodes and bone marrow, sites with good access to circulating antibodies) and small volume...... antitumor activity and is well tolerated. Clinical trials are underway to further improve upon treatment efficacy and patient selection. This review focuses on the recent advances of clinical PET/CT imaging and RIT of prostate cancer.......Prostate cancer is a common cancer in men and continues to be a major health problem. Imaging plays an important role in the clinical management of patients with prostate cancer. An important goal for prostate cancer imaging is more accurate disease characterization through the synthesis...

  12. Carbon Ion Radiotherapy in Advanced Hypofractionated Regimens for Prostate Cancer: From 20 to 16 Fractions

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Tohru [National Institute of Radiological Sciences, Chiba (Japan); Tsuji, Hiroshi, E-mail: h_tsuji@nirs.go.jp [National Institute of Radiological Sciences, Chiba (Japan); Kamada, Tadashi [National Institute of Radiological Sciences, Chiba (Japan); Akakura, Koichiro; Suzuki, Hiroyoshi; Shimazaki, Jun [Department of Urology, Graduate School of Medicine, Chiba University, Chiba (Japan); Tsujii, Hirohiko [National Institute of Radiological Sciences, Chiba (Japan)

    2012-11-15

    Purpose: To assess the effects of differences in dose fractionation on late radiation toxicity and biochemical control in patients with prostate cancer treated with carbon ion radiotherapy (C-ion RT). Methods and Materials: A total of 740 prostate cancer patients who received C-ion RT between April 2000 and February 2009 were analyzed. Of those, 664 patients followed for at least 1 year were analyzed with regard to late radiation toxicity. Biochemical relapse-free (BRF) and overall survival (OS) rates in patient subgroups with each dose-fractionation were analyzed. Results: Only 1 case of grade 3 genitourinary (GU) morbidity was observed in 20 fractions, and none of the patients developed higher grade morbidities. The incidence of late GU toxicity in patients treated with 16 fractions was lower than that of patients treated with 20 fractions. The OS rate and BRF rate of the entire group at 5 years were 95.2% and 89.7%, respectively. The 5-year BRF rate of the patients treated with 16 fractions of C-ion RT (88.5%) was comparable to that of the patients treated with 20 fractions (90.2%). Conclusion: C-ion RT of 57.6 GyE (the physical C-ion dose [Gy] Multiplication-Sign RBE) in 16 fractions could offer an even lower incidence of genitourinary toxicity and comparable BRF rate than that in 20 fractions. Advancement in hypofractionation could be safely achieved with C-ion RT for prostate cancer.

  13. 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.

  14. Progression-free and overall survival in metastatic castration-resistant prostate cancer treated with abiraterone acetate can be predicted with serial C11-acetate PET/CT.

    Science.gov (United States)

    Farnebo, Jacob; Wadelius, Agnes; Sandström, Per; Nilsson, Sten; Jacobsson, Hans; Blomqvist, Lennart; Ullén, Anders

    2016-08-01

    In this retrospective study, we evaluated the benefit of repeated carbon 11 (C11)-acetate positron emission tomography/computed tomography (PET/CT) to assess response in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA).A total of 30 patients with mCRPC were monitored with C11-acetate PET/CT and PSA levels during their treatment with AA. Retrospective evaluation of their response was made after 102 days (median; range 70-155) of treatment. Statistical analyses were employed to detect predictors of progression-free survival (PFS) and overall survival (OS), and potential correlation between serum levels of PSA, standardized uptake values (SUVpeak), and bone lesion index measured from PET were investigated.At follow-up 10 patients exhibited partial response (PR), 10 progressive disease (PD), and 10 stable disease (SD), as assessed by PET/CT. In survival analysis, both PR and PD were significantly associated with PFS and OS. CT response was also associated with OS, but only 19/30 patients demonstrated a lesion meeting target lesion criteria according to RECIST 1.1. No PET/CT baseline characteristic was significantly associated with PFS or OS. A PSA response (reduction in the level by >50%) could also predict PFS and OS. In the subgroup lacking a PSA response, those with PD had significantly shorter OS than those with PR or SD.PFS and OS in patients with mCRPC treated with AA can be predicted from repeated C11-acetate PET/CT. This may be of particular clinical value in patients who do not exhibit a PSA response to treatment. PMID:27495034

  15. Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline

    Science.gov (United States)

    Basch, Ethan; Loblaw, D. Andrew; Oliver, Thomas K.; Carducci, Michael; Chen, Ronald C.; Frame, James N.; Garrels, Kristina; Hotte, Sebastien; Kattan, Michael W.; Raghavan, Derek; Saad, Fred; Taplin, Mary-Ellen; Walker-Dilks, Cindy; Williams, James; Winquist, Eric; Bennett, Charles L.; Wootton, Ted; Rumble, R. Bryan; Dusetzina, Stacie B.; Virgo, Katherine S.

    2014-01-01

    Purpose To provide treatment recommendations for men with metastatic castration-resistant prostate cancer (CRPC). Methods The American Society of Clinical Oncology and Cancer Care Ontario convened an expert panel to develop evidence-based recommendations informed by a systematic review of the literature. Results When added to androgen deprivation, therapies demonstrating improved survival, improved quality of life (QOL), and favorable benefit-harm balance include abiraterone acetate/prednisone, enzalutamide, and radium-223 (223Ra; for men with predominantly bone metastases). Improved survival and QOL with moderate toxicity risk are associated with docetaxel/prednisone. For asymptomatic/minimally symptomatic men, improved survival with unclear QOL impact and low toxicity are associated with sipuleucel-T. For men who previously received docetaxel, improved survival, unclear QOL impact, and moderate to high toxicity risk are associated with cabazitaxel/prednisone. Modest QOL benefit (without survival benefit) and high toxicity risk are associated with mitoxantrone/prednisone after docetaxel. No benefit and excess toxicity are observed with bevacizumab, estramustine, and sunitinib. Recommendations Continue androgen deprivation (pharmaceutical or surgical) indefinitely. Abiraterone acetate/prednisone, enzalutamide, or 223Ra should be offered; docetaxel/prednisone should also be offered, accompanied by discussion of toxicity risk. Sipuleucel-T may be offered to asymptomatic/minimally symptomatic men. For men who have experienced progression with docetaxel, cabazitaxel may be offered, accompanied by discussion of toxicity risk. Mitoxantrone may be offered, accompanied by discussion of limited clinical benefit and toxicity risk. Ketoconazole or antiandrogens (eg, bicalutamide, flutamide, nilutamide) may be offered, accompanied by discussion of limited known clinical benefit. Bevacizumab, estramustine, and sunitinib should not be offered. There is insufficient evidence to

  16. A multicenter, randomized clinical trial comparing the three-weekly docetaxel regimen plus prednisone versus mitoxantone plus prednisone for Chinese patients with metastatic castration refractory prostate cancer.

    Directory of Open Access Journals (Sweden)

    Tie Zhou

    Full Text Available To explore the feasibility and efficacy of docetaxel plus prednisone for Chinese population with metastatic castration refractory prostate cancer (mCRPC.A total of 228 patients recruited from 15 centers were randomized to receive 10 cycles of D3P arm (docetaxel: 75 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily or M3P arm (mitoxantrone: 12 mg/m2, intravenous infusion, every three weeks; Prednisone 10mg orally given daily. Primary end point was overall survival, and secondary end points were events progression-free survival (PFS, response rate, response duration. Quality of life (QoL was also assessed in both treatment groups.The median overall survival was 21.88 months in D3P arm and 13.67 months in M3P arm (P = 0.0011, hazard ratio = 0.63, 95% confidence interval, 0.46-0.86. Subgroup analysis was consistent with the results of overall analysis. Events progression-free survival (pain, PSA, tumor and disease were significantly improved in D3P arm compared with M3P arm. PSA response rate was 35.11% for patients treated by D3P arm and 19.39% for M3P arm (P = 0.0155. Pain response rate was higher in D3P arm (61.11%, P = 0.0011 than in M3P (23.08% arm. No statistical differences were found between D3P arm and M3P arm for QoL, tumor response rate and response duration of PSA and pain. The tolerability and overall safety of D3P arm were generally comparable to that of M3P arm.Compared with M3P arm, D3P arm significantly prolonged overall survival for the Chinese patients with mCRPC and improved the response rate for PSA and pain.clinicaltrials.gov NCT00436839.

  17. Enzalutamide for treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel: U.S. Food and Drug Administration drug approval summary.

    Science.gov (United States)

    Ning, Yangmin M; Pierce, William; Maher, V Ellen; Karuri, Stella; Tang, Sheng-Hui; Chiu, Haw-Jyh; Palmby, Todd; Zirkelbach, Jeanne Fourie; Marathe, Dhananjay; Mehrotra, Nitin; Liu, Qi; Ghosh, Debasis; Cottrell, Christy L; Leighton, John; Sridhara, Rajeshwari; Ibrahim, Amna; Justice, Robert; Pazdur, Richard

    2013-11-15

    This article summarizes the regulatory evaluation that led to the full approval of enzalutamide (XTANDI, Medivation Inc.) by the U.S. Food and Drug Administration (FDA) on August 31, 2012, for the treatment of patients with metastatic castration-resistant prostate cancer who have previously received docetaxel. This approval was based on the results of a randomized, placebo-controlled trial which randomly allocated 1,199 patients with mCRPC who had received prior docetaxel to receive either enzalutamide, 160 mg orally once daily (n = 800), or placebo (n = 399). All patients were required to continue androgen deprivation therapy. The primary endpoint was overall survival. At the prespecified interim analysis, a statistically significant improvement in overall survival was demonstrated for the enzalutamide arm compared with the placebo arm [HR = 0.63; 95% confidence interval: 0.53-0.75; P < 0.0001]. The median overall survival durations were 18.4 months and 13.6 months in the enzalutamide and placebo arms, respectively. The most common adverse reactions (≥10%) included asthenia or fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, and upper respiratory infection. Seizures occurred in 0.9% of patients on enzalutamide compared with no patients on the placebo arm. Overall, the FDA's review and analyses of the submitted data confirmed that enzalutamide had a favorable benefit-risk profile in the study patient population, thus supporting its use for the approved indication. The recommended dose is 160 mg of enzalutamide administered orally once daily. Enzalutamide represents the third product that the FDA has approved in the same disease setting within a period of 2 years. Clin Cancer Res; 19(22); 6067-73. ©2013 AACR.

  18. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial

    NARCIS (Netherlands)

    Brose, M.S.; Nutting, C.M.; Jarzab, B.; Elisei, R.; Siena, S. Di; Bastholt, L.; Fouchardiere, C. de la; Pacini, F.; Paschke, R.; Shong, Y.K.; Sherman, S.I.; Smit, J.W.; Chung, J.; Kappeler, C.; Pena, C.; Molnar, I.; Schlumberger, M.J.

    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 treatm

  19. Optimal first-line chemotherapeutic treatment in patients with locally advanced or metastatic esophagogastric carcinoma : triplet versus doublet chemotherapy: a systematic literature review and meta-analysis

    NARCIS (Netherlands)

    Mohammad, N Haj; ter Veer, E; Ngai, L; Mali, R; van Oijen, M G H; van Laarhoven, H W M

    2015-01-01

    There is a debate whether triplet or doublet chemotherapy should be used as a first-line treatment in patients with advanced or metastatic esophagogastric cancer. Therefore, here we will review the available literature to assess the efficacy and safety of triplet versus doublet chemotherapy as a fir

  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. Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

    Science.gov (United States)

    2016-05-16

    Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; 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 Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

  3. 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。

  4. External beam radiation therapy for prostate cancer

    International Nuclear Information System (INIS)

    Purpose/Objectives: The intent of this course is to review the issues involved in the management of non-metastatic adenocarcinoma of the prostate. -- The value of pre-treatment prognostic factors including stage, grade and PSA value will be presented, and their value in determining therapeutic strategies will be discussed. -- Controversies involving the simulation process and treatment design will be presented. The value of CT scanning, Beams-Eye View, 3-D planning, intravesicle, intraurethral and rectal contrast will be presented. The significance of prostate and patient movement and strategies for dealing with them will be presented. -- The management of low stage, low to intermediate grade prostate cancer will be discussed. The dose, volume and timing of irradiation will be discussed as will the role of neo-adjuvant hormonal therapy, neutron irradiation and brachytherapy. The current status of radical prostatectomy and cryotherapy will be summarized. Treatment of locally advanced, poorly differentiated prostate cancer will be presented including a discussion of neo-adjuvant and adjuvant hormones, dose-escalation and neutron irradiation. -- Strategies for post-radiation failures will be presented including data on cryotherapy, salvage prostatectomy and hormonal therapy (immediate, delayed and/or intermittent). New areas for investigation will be reviewed. -- The management of patients post prostatectomy will be reviewed. Data on adjuvant radiation and therapeutic radiation for biochemical or clinically relapsed patients will be presented. This course hopes to present a realistic and pragmatic overview for treating patients with non-metastatic prostatic cancer

  5. HIGH DOSE IFOSFAMIDE, DOXORUBICIN, DACARBAZINE AND G-CSF FOR PATIENTS WITH METASTATIC OR LOCALLY ADVANCED SOFT TISSUE SARCOMA

    Institute of Scientific and Technical Information of China (English)

    LIN Tong-yu; GUANG Zhong-zhen; SU Yi-sun; ZHOU Zhong-mei; LIU Dong-geng

    1999-01-01

    Objective: A pilot study to test the feasibility and efficacy of high dose IFO and standard dose ADR and DTIC with G-CSF support in treatment of advanced soft tissue sarcoma (STS). Methods: 35 patients of no prior chemotherapy with metastatic or locally advanced unresectable STS were treated by this regimen, including 18 rhabdomyosarcomas, 7 malignant fibrous histiocytomas, 2 neurofibrosarcomas, 2 fibrosarcomas, 2 leiomyosarcomas, 2 synoviosarcomas, and 2 malignant hemangiopericytomas.IFO dose was 2 g/m2 on day 1-5 (with mesna uroprotection),ADR 50mg/m2 on day 1 and DTIC 250 mg/m2 on day 1-5.G-CSF (2 μg/kg/d) was administered on day 6 to 15 or until recovery of leukocytes account. The cycles were repeated every 3 weeks. Result: There were five complete responses (CR including pathologic CR) and eleven partial responses for overall 46% objective response rate. Most responses were observed within two cycles. The median survival was 15 months. Following CR, two patients remain disease free at 45 and 28 months, respectively. 6/120 (5%) cycles were complicated by grade Ⅳ neutropenia, 46/120 (38%) cycles had grade Ⅲ neutropenia. No patients had treatmentrelated deaths. Nonhematologic toxicity consisted predominantly of anorexia and vomiting. No other severe toxicities were seen, especially no severe cardiotoxicity.Conclusion: This regimen is well tolerated and has substantial benefits for patients with advanced soft tissue sarcomas.

  6. Reviews on Abiraterone Acetate Treatment on Metastatic Castration-Resistant Prostate Cancer%醋酸阿比特龙治疗转移性去势抵抗性前列腺癌综述

    Institute of Scientific and Technical Information of China (English)

    陈文东; 孙艳; 王沭; 杜芬

    2016-01-01

    Advanced prostate cancer (PCa) eventually progresses to castrate-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT) because the adrenal and prostate cancer cells still generate androgen that stimulates the growth of tumor cells. Abiraterone acetate is a specific inhibitor of CYP17 that blocks testicular, adrenal and tumor androgen biosynthesis. Large phase III randomized clinical trials have proved that abiraterone acetate improved overall survival, delayed disease progress, controlled disease-related symptoms, and improved quality of life in metastatic CRPC (mCRPC) patients without chemotherapy or with failed chemotherapy. The published economic analysis suggested that the combination of abiraterone and low dose prednisone was cost-effective compared with other new therapies in post-chemotherapy mCRPC patients. Additionally, abiraterone acetate was found to have minimal budget impact on health plans likely due to small size of patients and saved health resources utilization associated with administration and safety of abiraterone acetate. The treatments for mCRPC in China are limited and the launch of using abiraterone acetate provided patients and health care providers a new treatment option.%经雄激素剥夺疗法(ADT)治疗后,晚期前列腺癌(PCa)最终进展为去势抵抗性前列腺癌(CRPC)的原因是睾丸外器官(肾上腺)和前列腺癌细胞本身仍有合成雄激素的能力,继续刺激癌细胞的生长。醋酸阿比特龙是CYP17酶的选择性抑制剂,能全面阻断睾丸、肾上腺和前列腺癌细胞中的雄激素生物合成。大型三期随机对照临床试验均已证明,对未经化疗或者化疗失败的转移性CRPC(mCRPC)患者,醋酸阿比特龙联合小剂量泼尼松能够显著提高患者生存时间、延缓疾病进展、缓解疾病症状、提高患者生命质量。已发表的经济学分析表明,在化疗后的人群中,阿比特龙方案相对于其

  7. 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.

  8. PHARMACODYNAMIC EQUIVALENCE OF USING 3-MONTH AND 28-DAY SUSTAINED-RELEASE DECAPEPTYL DEPOT FORMULATIONS IN PATIENTS WITH ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    P. Teillac

    2009-01-01

    Full Text Available Objective: to evaluate the pharmacodynamic equivalence of 3-month and 28-day formulations of tryptoreline, a sustained-release luteininghormone (LH-releasing hormone analogue.Subjects and methods. The patients who had a verified diagnosis of locally advanced or metastatic prostate cancer were randomized intogroups to have either one injection of a 3-month dosage form (n = 63 or 3 injections of a 28-day formulation at 28-day intervals (n = 68.The onset rate of drug-induced castration, which was defined as a percentage of the patients achieving a plasma testosterone level of ≤0.5ng/ml, was compared on day 84 (i.e. thrice every 28 days. The plasma profiles of testosterone, LH, and tryptoreline, as well as the changesin the plasma concentration of prostate-specific antigen (PCA from the baseline values were estimated within 3 months (from the initiationof therapy to day 91.Results. In the 3-month and 28-day groups, the onset rate of drug-induced castration was 98 and 96%, respectively (at confidenceintervals (94.2% bilaterally in [-8.1%; 9.6%]. The median time for drug-induced castration was 18.8 and 18.5 days, respective-ly (p = 0.86; log-rank test. The ratios of the mean peak plasma concentrations to AUC91 of the two formulations for testosteroneand LH were within 0.80; 1.25 equivalence interval. By day 91, the mean PSA level was decreased by 91.0 and 91.7%, respec-tively (p = 0.73.Conclusion. The use of the two formulations during 3 months is pharmacologically equal.  

  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. PMID:27151773

  10. Management of metastatic malignant thymoma with advanced radiation and chemotherapy techniques: report of a rare case

    OpenAIRE

    D’Andrea, Mark A; Reddy, G. Kesava

    2015-01-01

    Malignant thymomas are rare epithelial neoplasms of the anterior superior mediastinum that are typically invasive in nature and have a higher risk of relapse that may ultimately lead to death. Here we report a case of an advanced malignant thymoma that was successfully treated with neoadjuvant chemotherapy followed by surgical resection and subsequently with advanced and novel radiation therapy techniques. A 65-year-old male was diagnosed with a stage IV malignant thymoma with multiple metast...

  11. 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.

  12. 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....

  13. {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

  14. 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.

  15. 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.

  16. Hedgehog overexpression leads to the formation of prostate cancer stem cells with metastatic property irrespective of androgen receptor expression in the mouse model

    OpenAIRE

    Chang Chin-Pao; Chen Ying-Yu; Tsao Zih-Jay; Wu Chia-Yung; Chen Bo-Yie; Chang Han-Hsin; Yang Chi-Rei; Lin David

    2011-01-01

    Abstract Background Hedgehog signalling has been implicated in prostate tumorigenesis in human subjects and mouse models, but its effects on transforming normal basal/stem cells toward malignant cancer stem cells remain poorly understood. Methods We produced pCX-shh-IG mice that overexpress Hedgehog protein persistently in adult prostates, allowing for elucidation of the mechanism during prostate cancer initiation and progression. Various markers were used to characterize and confirm the tran...

  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. TMPRSS2-ERG gene fusion in metastatic prostate cancers: a study of fine needle aspiration specimens%TMPRSS2-ERG融合基因在转移性前列腺癌中的表达

    Institute of Scientific and Technical Information of China (English)

    肖立; 朱雄增; WANG Yan; GONG Yun; GUO C Charles

    2011-01-01

    目的 检测转移性前列腺癌中TMPRSS2-ERG基因融合的发生率,探讨ERG基因重排在前列腺癌进展中的作用.方法 收集32例由细针穿刺诊断的转移性前列腺癌,穿刺部位包括盆腔及远处淋巴结、肝、骨、甲状腺等,回顾相关临床病理学资料.免疫组织化学采用EnVision法标记前列腺特异性抗原、突触素和嗜铬粒素A.运用ERG分离断裂探针荧光原位杂交(FISH)方法,检测细胞学蜡块中转移性前列腺癌的TMPRSS2-ERG基因融合.结果 患者平均年龄67岁,26例有经治疗的前列腺癌病史,其余6例以转移性病灶为首发症状.11例转移灶形态上提示为前列腺小细胞癌,免疫组织化学突触素(9/9)、嗜铬粒素A(7/8)阳性,前列腺特异性抗原(7/7)阴性.FISH分析显示,共有31.3%(10/32)转移性前列腺癌存在TMPRSS2-ERG基因融合,其中6例为ERG基因5′端缺失性重排;8例ERG基因重排伴拷贝数增加.11例转移性前列腺小细胞癌中,5例显示TMPRSS2-ERG基因融合,3例为5′端缺失性重排伴拷贝数增加.结论 细胞学细针穿刺标本可用于检测TMPRSS2-ERG融合基因状态;转移性前列腺癌常表达多拷贝ERG重排基因;即使发生小细胞癌转变后,仍然保持融合基因状态;TMPRSS2-ERG融合基因可用于区分前列腺来源的小细胞癌.%Objective To investigate diagnostic values of the detection of TMPRSS2-ERG gene fusion in metastatic prostate cancer. Methods A total of 32 fine needle aspiration (FNA) specimens of metastatic prostate carcinomas were retrieved from the pathology files at MD Anderson Cancer Center. The metastatic sites included the pelvic and remote lymph nodes, liver, bone, and thyroid gland. Immunohistochemical staining for PSA, PAP, synaptophysin, chromogranin A was performed. TMPRSS2-ERG gene fusion was evaluated on sections of cell blocks by fluorescence in situ hybridization (FISH) using ERG gene break-apart probes. Results The mean age of the patients was 67

  19. Phase I study of intermittent and chronomodulated oral therapy with capecitabine in patients with advanced and/or metastatic cancer

    International Nuclear Information System (INIS)

    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. 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. 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. 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

  20. Biochemical Bone Markers in Prostate Cancer Patients with Local and Advanced Bone Metastates

    OpenAIRE

    AKSOY, Hülya

    2001-01-01

    In the present study involving patients with bone metastases arising from prostate cancer, we measured urinary deoxypyridinoline (DPD) as a marker of collagen breakdown activity, serum total and bone-specific alkaline phosphatase activities and serum prostate specific antigen (PSA). This study included 20 patients with benign prostate hyperplasia (BPH) and 23 patients with carcinoma, 11 of had with bone metastases. DPD excretion in urine was significantly greater in prostate cancer patients w...

  1. 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

  2. Pre-Operative Prediction of Advanced Prostatic Cancer Using Clinical Decision Support Systems: Accuracy Comparison between Support Vector Machine and Artificial Neural Network

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Youn; Moon, Sung Kyoung; Hwang, Sung Il; Sung, Chang Kyu; Cho, Jeong Yeon; Kim, Seung Hyup; Lee, Hak Jong [Seoul National University College of Medicine, Seoul (Korea, Republic of); Jung, Dae Chul [National Cancer Center, Ilsan (Korea, Republic of); Lee, Ji Won [Kangwon National University College of Medicine, Chuncheon (Korea, Republic of)

    2011-10-15

    The purpose of the current study was to develop support vector machine (SVM) and artificial neural network (ANN) models for the pre-operative prediction of advanced prostate cancer by using the parameters acquired from transrectal ultrasound (TRUS)-guided prostate biopsies, and to compare the accuracies between the two models. Five hundred thirty-two consecutive patients who underwent prostate biopsies and prostatectomies for prostate cancer were divided into the training and test groups (n = 300 versus n 232). From the data in the training group, two clinical decision support systems (CDSSs-[SVM and ANN]) were constructed with input (age, prostate specific antigen level, digital rectal examination, and five biopsy parameters) and output data (the probability for advanced prostate cancer [> pT3a]). From the data of the test group, the accuracy of output data was evaluated. The areas under the receiver operating characteristic (ROC) curve (AUC) were calculated to summarize the overall performances, and a comparison of the ROC curves was performed (p < 0.05). The AUC of SVM and ANN is 0.805 and 0.719, respectively (p = 0.020), in the pre-operative prediction of advanced prostate cancer. Te performance of SVM is superior to ANN in the pre-operative prediction of advanced prostate cancer.

  3. 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

  4. 68Ga-PSMA-11 PET Represents the Tumoricidal Effect of 223Ra in a Patient With Castrate-Resistant Metastatic Prostate Cancer.

    Science.gov (United States)

    Ahmadzadehfar, Hojjat; Schlenkhoff, Carl Diedrich; Rogenhofer, Sebastian; Yordanova, Anna; Essler, Markus

    2016-09-01

    A 64-year-old man with prostate cancer and an increasing prostate-specific antigen (PSA) level under therapy with abiraterone acetate underwent a therapy with Ra. Before the first therapy and 4 weeks after the last cycle, the patient underwent Ga-PSMA PET, which showed a clear response of bone metastases. PMID:27405025

  5. Update in palliative management of hormone refractory cancer of prostate

    OpenAIRE

    Singh, Pratipal; Srivastava, Aneesh

    2007-01-01

    Hormone refractory prostate cancer (HRPC) is an incurable disease and as in the pressure sensitive adhesive era the median survival of patients is increasing, these men increasingly develop symptomatic problems as a result of advanced local and or metastatic disease during their progression to death. Recently, it has been shown that it is possible to improve survival in this group of patients with use of chemotherapy which reinforces the need of better options in palliative care. We discus th...

  6. 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

  7. Phorbol ester stimulates ethanolamine release from the metastatic basal prostate cancer cell line PC3 but not from prostate epithelial cell lines LNCaP and P4E6

    OpenAIRE

    Schmitt, J; Noble, A.; Otsuka, M; Berry, P.; Maitland, N J; Rumsby, M.G.

    2014-01-01

    Background: Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethanolamine (Etn) metabolites released to the medium. Methods: Prostate epithelial cell lines P4E6, LNCaP and PC3 were models of prostate cancer (PCa). PNT2C2 and PNT1A were models ...

  8. Ductal adenocarcinoma of the prostate: histogenesis, biology and clinicopathological features.

    Science.gov (United States)

    Seipel, Amanda H; Delahunt, Brett; Samaratunga, Hemamali; Egevad, Lars

    2016-08-01

    Ductal adenocarcinoma of the prostate (DAC) is recognised as a subtype of prostatic adenocarcinoma, but its diagnostic criteria and biology remain controversial. DAC was first thought to stem from Müllerian duct remnants, but further studies suggest a prostatic origin. DAC is composed of tall, columnar, pseudostratified epithelium with a papillary, cribriform, glandular or solid architecture. The diagnosis is based on morphology alone with papillary architecture being the most helpful diagnostic feature. The tumour is rare in a pure form and most cases are combined with acinar adenocarcinoma. The most common differential diagnoses of DAC are intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia. Patients often present at an advanced clinicopathological stage. High rates of extra-prostatic extension, seminal vesicle invasion, local and regional metastases, and positive surgical margins are seen after radical prostatectomy. DAC metastasises to sites that are less commonly seen for prostate cancer such as lung, brain, testis and penis. The morphology and the unusual metastatic locations make the accurate diagnosis of metastases challenging, but a positive immunostain for prostate specific markers may be helpful. The correct identification of DAC has implications for treatment as well as outcome. PMID:27321992

  9. 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......-week schedule and comparisons of the feasibility and toxicity between the two schedules have not previously been published. MATERIAL AND METHODS: We performed a retrospective analysis of patients with stage IV TCC, treated with GC by a standard 4-week or by an alternative 3-week schedule. RESULTS...

  10. Subgroup Analyses from a Phase 3, Open-Label, Randomized Study of Eribulin Mesylate Versus Capecitabine in Pretreated Patients with Advanced or Metastatic Breast Cancer

    Science.gov (United States)

    Twelves, Chris; Awada, Ahmad; Cortes, Javier; Yelle, Louise; Velikova, Galina; Olivo, Martin S.; Song, James; Dutcus, Corina E.; Kaufman, Peter A.

    2016-01-01

    PURPOSE AND METHODS Our secondary analyses compared survival with eribulin versus capecitabine in various patient subgroups from a phase 3, open-label, randomized study. Eligible women aged ≥18 years with advanced/metastatic breast cancer and ≤3 prior chemotherapies (≤2 for advanced/metastatic disease), including an anthracycline and taxane, were randomized 1:1 to intravenous eribulin mesylate 1.4 mg/m2 on days 1 and 8 or twice-daily oral capecitabine 1250 mg/m2 on days 1–14 (21-day cycles). RESULTS In the intent-to-treat population (eribulin 554 and capecitabine 548), overall survival appeared longer with eribulin than capecitabine in various subgroups, including patients with human epidermal growth factor receptor 2-negative (15.9 versus 13.5 months, respectively), estrogen receptor-negative (14.4 versus 10.5 months, respectively), and triple-negative (14.4 versus 9.4 months, respectively) disease. Progression-free survival was similar between the treatment arms. CONCLUSIONS Patients with advanced/metastatic breast cancer and human epidermal growth factor receptor 2-, estrogen receptor-, or triple-negative disease may gain particular benefit from eribulin as first-, second-, and third-line chemotherapies. TRIAL REGISTRATION (PRIMARY STUDY) This study reports the subgroup analyses of eribulin versus capecitabine from a phase 3, open-label, randomized study (www.clinicaltrials.gov; ClinicalTrials.gov identifier: NCT00337103). PMID:27398025

  11. Prostate cancer is not breast cancer

    Directory of Open Access Journals (Sweden)

    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.

  12. SUV39H1/H3K9me3 attenuates sulforaphane-induced apoptotic signaling in PC3 prostate cancer cells

    OpenAIRE

    Watson, G.W.; Wickramasekara, S.; Palomera-Sanchez, Z; Black, C; Maier, C S; Williams, D.E.; Dashwood, R. H.; Ho, E.

    2014-01-01

    The isothiocyanate sulforaphane is a promising molecule for development as a therapeutic agent for patients with metastatic prostate cancer. Sulforaphane induces apoptosis in advanced prostate cancer cells, slows disease progression in vivo and is well tolerated at pharmacological doses. However, the underlying mechanism(s) responsible for cancer suppression remain to be fully elucidated. In this investigation we demonstrate that sulforaphane induces posttranslational modification of histone ...

  13. Evaluation of Alpha-Therapy with Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—the Role of Gamma Scintigraphy in Dosimetry and Pharmacokinetics

    Directory of Open Access Journals (Sweden)

    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

  14. 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

  15. Vaccine Therapy With or Without Sargramostim in Treating Patients With Advanced or Metastatic Cancer

    Science.gov (United States)

    2013-01-24

    Adenocarcinoma of the Colon; Adenocarcinoma of the Gallbladder; Adenocarcinoma of the Pancreas; Adenocarcinoma of the Rectum; Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Diffuse Adenocarcinoma of the Stomach; Intestinal Adenocarcinoma of the Stomach; Male Breast Cancer; Mixed Adenocarcinoma of the Stomach; Ovarian Endometrioid Adenocarcinoma; Paget Disease of the Breast With Intraductal Carcinoma; Paget Disease of the Breast With Invasive Ductal Carcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Breast Cancer; Recurrent Colon Cancer; Recurrent Gallbladder Cancer; Recurrent Gastric Cancer; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Pancreatic Cancer; Recurrent Rectal Cancer; Recurrent Salivary Gland Cancer; Salivary Gland Adenocarcinoma; Stage II Malignant Testicular Germ Cell Tumor; Stage II Pancreatic Cancer; Stage III Colon Cancer; Stage III Gastric Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Pancreatic Cancer; Stage III Rectal Cancer; Stage III Salivary Gland Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Pancreatic Cancer; Stage IV Rectal Cancer; Stage IV Salivary Gland Cancer; Thyroid Gland Medullary Carcinoma; Unresectable Gallbladder Cancer

  16. 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.

  17. Contemporary Management of Prostate Cancer.

    Science.gov (United States)

    Cotter, Katherine; Konety, Badrinath; Ordonez, Maria A

    2016-01-01

    Prostate cancer represents a spectrum ranging from low-grade, localized tumors to devastating metastatic disease. We discuss the general options for treatment and recent developments in the field. PMID:26949522

  18. 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.)

  19. RHAMM (CD168) Is Overexpressed at the Protein Level and May Constitute an Immunogenic Antigen in Advanced Prostate Cancer Disease

    OpenAIRE

    Kilian M. Gust; Hofer, Matthias D; Sven R. Perner; Robert Kim; Arul M. Chinnaiyan; Sooryanarayana Varambally; Peter Moller; Ludwig Rinnab; Rubin, Mark A; Jochen Greiner; Michael Schmitt; Rainer Kuefer; Mark Ringhoffer

    2009-01-01

    Localized prostate cancer (CaP) can be cured using several strategies. However, the need to identify active substances in advanced tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human tumor antigen-targeted therapy, which is recognized by T cells or antibodies. We used data mining of the Cancer Immunome Database (CID), which comprises potential immunologic targets identified by serological screening of expression libraries. Candidat...

  20. EFFICACY OF ZOLEDRONIC ACID IN THE PREVENTION OF BONE METASTASES IN PATIENTS WITH LOCALLY ADVANCED PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    T. N. Musaev

    2014-07-01

    Full Text Available The analysis of the performed study has established that zoledronic acid is an effective agent in multimodality therapy for locally advanced prostate cancer (PC and allows long-term stabilization of bone tissue. In addition, there is evidence for the efficacy of zoledronic acid in preventing bone metastases (BM and increasing the time to the first BM. The currently accumulated experience with zoledronic acid used in PC permits one to consider its use as standard concomitant therapy.

  1. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours.

    Science.gov (United States)

    Soo, Ross Andrew; Syn, Nicholas; Lee, Soo-Chin; Wang, Lingzhi; Lim, Xn-Yii; Loh, Marie; Tan, Sing-Huang; Zee, Ying-Kiat; Wong, Andrea Li-Ann; Chuah, Benjamin; Chan, Daniel; Lim, Siew-Eng; Goh, Boon-Cher; Soong, Richie; Yong, Wei-Peng

    2016-01-01

    The FDA-approved starting dosage of capecitabine is 1,250 mg/m(2), and market research indicates that U.S. physicians routinely prescribe 1,000 mg/m(2). Retrospective analyses however report reduced toxicity and efficacy in a subset of patients with the 3R/3R genotype of the thymidylate synthase gene enhancer region (TSER). This study sought to develop TSER genotype-specific guidelines for capecitabine dosing. Capecitabine was dose-escalated in advanced and/or metastatic cancer patients with TSER 3R/3R (Group A; N = 18) or 2R/2R + 2R/3R (Group B; N = 5) from 1,250 to 1,625 mg/m(2) b.i.d., every 2 weeks on/1 week off for up to 8 cycles. Parent and metabolites pharmacokinetics, adverse events, and tumour response were assessed. The maximum tolerated and recommended doses in 3R/3R patients are 1,625 mg/m(2) and 1,500 mg/m(2). At 1,500 mg/m(2), one in nine 3R/3R patients experienced a dose-limiting toxicity. Dosing guidelines for 2R/2R + 2R/3R remain undetermined due to poor accrual. The results indicate that 3R/3R patients may be amenable to 1,500 mg/m(2) b.i.d. on an intermittent schedule, and is the first to prospectively validate the utility of TSER pharmacogenetic-testing before capecitabine treatment. PMID:27296624

  2. 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

  3. Tobacco smoking, polymorphisms in carcinogen metabolism enzyme genes, and risk of localized and advanced prostate cancer: results from the California Collaborative Prostate Cancer Study

    International Nuclear Information System (INIS)

    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

  4. 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....

  5. 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....

  6. 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

  7. Vascular endothelial growth factor (VEGF) expression in locally advanced prostate cancer: secondary analysis of radiation therapy oncology group (RTOG) 8610

    International Nuclear Information System (INIS)

    Angiogenesis is a key element in solid-tumor growth, invasion, and metastasis. VEGF is among the most potent angiogenic factor thus far detected. The aim of the present study is to explore the potential of VEGF (also known as VEGF-A) as a prognostic and predictive biomarker among men with locally advanced prostate cancer. The analysis was performed using patients enrolled on RTOG 8610, a phase III randomized control trial of radiation therapy alone (Arm 1) versus short-term neoadjuvant and concurrent androgen deprivation and radiation therapy (Arm 2) in men with locally advanced prostate carcinoma. Tissue samples were obtained from the RTOG tissue repository. Hematoxylin and eosin slides were reviewed, and paraffin blocks were immunohistochemically stained for VEGF expression and graded by Intensity score (0–3). Cox or Fine and Gray’s proportional hazards models were used. Sufficient pathologic material was available from 103 (23%) of the 456 analyzable patients enrolled in the RTOG 8610 study. There were no statistically significant differences in the pre-treatment characteristics between the patient groups with and without VEGF intensity data. Median follow-up for all surviving patients with VEGF intensity data is 12.2 years. Univariate and multivariate analyses demonstrated no statistically significant correlation between the intensity of VEGF expression and overall survival, distant metastasis, local progression, disease-free survival, or biochemical failure. VEGF expression was also not statistically significantly associated with any of the endpoints when analyzed by treatment arm. This study revealed no statistically significant prognostic or predictive value of VEGF expression for locally advanced prostate cancer. This analysis is among one of the largest sample bases with long-term follow-up in a well-characterized patient population. There is an urgent need to establish multidisciplinary initiatives for coordinating further research in the area of

  8. A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6

    DEFF Research Database (Denmark)

    Iversen, P; Tammela, T L J; Vaage, S;

    2002-01-01

    To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer.......To assess the efficacy and tolerability of bicalutamide 150 mg ('Casodex'(1)) as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with early (T1b-T4, any N, M0) prostate cancer....

  9. TMPRSS2:ERG融合基因与前列腺原位癌和外周转移癌的相关性研究%Relationship between TMPRSS2:ERG fusion gene and primary and metastatic prostate cancer

    Institute of Scientific and Technical Information of China (English)

    毛易捷; 史伟峰; 李青

    2013-01-01

    Objective To evaluate the relationship between primary and metastatic prostate cancers (PCa) with fusion gene of transmembrane protease, serine 2(TMPRSS2) gene and ETS related gene(ERG).Methods Fluorescence in situ hybridization was used to evaluated the rearrangement of ERG gene(TMPRSS2:ERG fusion gene) in 24 patients with PCa.Results In 6 patients with primary PCa, 4 cases were with TMPRSS2:ERG fusion gene.In 18 patients with metastatic PCa, 14 cases were with this fusion gene.In multifocal prostate cancer, the status of this fusion gene was concordant between primary tumor focus and metastasis in all cases.Conclusion There might be a close relationship between TMPRSS2: ERG fusion gene and primary and metastatic PCa.Positivity of this fusion gene could suggest the susceptibility of metastasis, which lead to death.%目的 分析跨膜丝氨酸蛋白酶2 (TMPRSS2)基因和ETS转录因子家族成员相关基因(ERG)融合基因与前列腺原位癌和外周转移癌的相关性.方法 采用荧光原位杂交技术对24例前列腺癌(PCa)患者组织标本进行TMPRSS2:ERG融合基因检测,评价TMPRSS2:ERG与前列腺原位癌和外周转移癌的相关性.结果 6例PCa原发癌患者中,4例检出TMPRSS2:ERG融合基因;18例转移性PCa患者中,14例检出该融合基因.外周淋巴结组织标本TMPRSS2:ERG融合基因阳性率为100%(8/8).14例融合基因阳性转移性PCa患者原发病灶和转移病灶具有一致的融合基因情况.结论 TMPRSS2:ERG融合基因具有较高的PCa诊断特异性和敏感性;应对该融合基因阳性患者尽早采取综合、有效的治疗措施,从而延长患者生存期.

  10. 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.

  11. New advances in genitourinary cancer: evidence gathered in 2014.

    Science.gov (United States)

    Suárez, C; Puente, J; Gallardo, E; Méndez-Vidal, M J; Climent, M A; León, L; Olmos, D; García del Muro, X; González-Billalabeitia, E; Grande, E; Bellmunt, J; Mellado, B; Maroto, P; González del Alba, A

    2015-09-01

    This review provides updated information published in 2014 regarding advances and major achievements in genitourinary cancer. Sections include the best in prostate cancer, renal cancer, bladder cancer, and germ cell tumors. In the field of prostate cancer, data related to treatment approach of hormone-sensitive disease, castrate-resistant prostate cancer, mechanisms of resistance, new drugs, and molecular research are presented. In relation to renal cancer, relevant aspects in the treatment of advanced renal cell carcinoma, immunotherapy, and molecular research, including angiogenesis and von Hippel-Lindau gene, molecular biology of non-clear cell histologies, and epigenetics of clear renal cell cancer are described. New strategies in the management of muscle-invasive localized bladder cancer and metastatic disease are reported as well as salient findings of biomolecular research in urothelial cancer. Some approaches intended to improve outcomes in poor prognosis patients with metastatic germ cell cancer are also reported. Results of clinical trials in these areas are discussed. PMID:26227584

  12. 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

  13. 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.

  14. Metformin and prostate cancer stem cells: a novel therapeutic target.

    Science.gov (United States)

    Mayer, M J; Klotz, L H; Venkateswaran, V

    2015-12-01

    Prostate cancer is the second most frequently diagnosed cancer in the world. Localized disease can be effectively treated with radiation therapy or radical prostatectomy. However, advanced prostate cancer is more difficult to treat and if metastatic, is incurable. There is a need for more effective therapy for advanced prostate cancer. One potential target is the cancer stem cell (CSC). CSCs have been described in several solid tumors, including prostate cancer, and contribute to therapeutic resistance and tumor recurrence. Metformin, a common oral biguanide used to treat type 2 diabetes, has been demonstrated to have anti-neoplastic effects. Specifically, metformin targets CSCs in breast cancer, pancreatic cancer, glioblastoma and colon cancer. Metformin acts directly on the mitochondria to inhibit oxidative phosphorylation and reduce mitochondrial ATP production. This forces tumor cells to compensate by increasing the rate of glycolysis. CSCs rely heavily on mitochondrial oxidative phosphorylation for energy production. The glycolytic switch results in an energy crisis in these cells. Metformin could be used to exploit this metabolic weakness in CSCs. This would increase CSC sensitivity to conventional cancer therapies, circumventing treatment resistance and enhancing treatment efficacy. This review will explore the characteristics of prostate CSCs, their role in tumor propagation and therapeutic resistance and the role of metformin as a potential prostate CSC sensitizer to current anticancer therapies. PMID:26215782

  15. IGFBP-3 is a Metastasis Suppression Gene in Prostate Cancer

    OpenAIRE

    Mehta, Hemal H.; Gao, Qinglei; Galet, Colette; Paharkova, Vladislava; Wan, Junxiang; Said, Jonathan; Sohn, Joanne J.; Lawson, Gregory; Cohen, Pinchas; Cobb, Laura J.; Lee, Kuk-Wha

    2011-01-01

    The insulin-like growth factor binding protein IGFBP-3 is a pro-apoptotic and anti-angiogenic protein in prostate cancer (CaP). Epidemiological studies suggest that low IGFBP-3 is associated with greater risk of aggressive, metastatic prostate cancers, but in vivo functional data are lacking. Here we show that mice that are genetically deficient in IGFBP-3 exhibit weaker growth of primary prostate tumors growth but higher incidence of metastatic disease. Prostates in IGFBP-3 knockout mice (IG...

  16. 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)

  17. Oncogenic herpesvirus HHV-8 promotes androgen-independent prostate cancer growth.

    Science.gov (United States)

    Mygatt, Justin G; Singhal, Adit; Sukumar, Gauthaman; Dalgard, Clifton L; Kaleeba, Johnan A R

    2013-09-15

    Mechanisms underlying progression to androgen-independent prostate cancer following radical ablation therapy remain poorly defined. Although intraprostatic infections have been highlighted as potential cofactors, pathogen influences on pathways that support tumor regrowth are not known. To explore this provocative concept, we derived androgen-sensitive and -insensitive prostate epithelial cells persistently infected with human herpesvirus 8 (HHV-8), an oncogenic herpesvirus that has been detected in normal prostate epithelium, prostate adenocarcinoma, and biologic fluids of patients with prostate cancer, to explore its effects on transition to hormone-refractory disease. Strikingly, we found that HHV-8 infection of androgen-sensitive prostate cancer cells conferred the capacity for androgen-independent growth. This effect was associated with altered expression and transcriptional activity of the androgen receptor (AR). However, HHV-8 infection bypassed AR signaling by promoting enhancer of zeste homolog 2 (EZH2)-mediated epigenetic silencing of tumor-suppressor genes, including MSMB and DAB2IP that are often inactivated in advanced disease. Furthermore, we found that HHV-8 triggered epithelial-to-mesenchymal transition. Although HHV-8 has not been linked etiologically to prostate cancer, virologic outcomes revealed by our study provide mechanistic insight into how intraprostatic infections could constitute risk for progression to androgen-independent metastatic disease where EZH2 has been implicated. Taken together, our findings prompt further evaluations of the relationship between HHV-8 infections and risk of advanced prostate cancer. PMID:24005834

  18. Chemotherapy in Prostate Cancer.

    Science.gov (United States)

    Hurwitz, Michael

    2015-10-01

    For approximately a decade, chemotherapy has been shown to prolong life in patients with metastatic castration-resistant prostate cancer (mCRPC). Since that time, however, only two agents have proven to prolong life (docetaxel and cabazitaxel). However, in the last year, the addition of chemotherapy to primary hormonal therapy became a standard of care for high-volume castration-sensitive metastatic disease. Here I will review current prostate cancer chemotherapies, mechanisms of resistance to those therapies, and ongoing clinical studies of chemotherapy combinations and novel chemotherapeutics. PMID:26216506

  19. Palliative chemotherapy followed by consolidation radiotherapy in patients with advanced and metastatic non-small cell lung cancer not suitable for radical treatment

    Institute of Scientific and Technical Information of China (English)

    Hany Eldeeb; Philip Gamileri; Ghoi Mak

    2012-01-01

    Objective: This is a retrospective study to assess the effectiveness of consolidation radiotherapy (CRT) following palliative chemotherapy in patients with metastatic or locally advanced non-small cell lung cancer (NSCLC) who are not suitable for radical treatment. Methods: This study involved retrospective analysis of a prospective database of Northampton Oncology Centre from January 2005 to December 2010,63 patients with advanced/metastatic NSCLC treated at the oncology centre were enrolled. Patients were either treated with high dose (39/36 Gy /13-12 fractions, group 1) or low dose (20 Gy / 5 fractions, group 2) CRT or those were not offered any CRT (group 3). Results: There was no significant difference between the three groups as regard age, sex, performance status, comorbidities or chemotherapy given. However there was a statistically significant difference as regard the stage P = 0.009 with more stage IV patients at group Ⅱ and Ⅲ compared to group l. The mean survival for the three groups was 27 months, 14 months &15 months, respectively. There was a statistically significant improvement of survival in patients treated with high dose palliative CRT compared to the other two groups (P = 0.006). In multivariate analysis only the radiotherapy dose remains as the only statistical significant factor affecting the survival with hazard ratio 0.372 and confidence interval (0.147-0.726). Conclusion: Despite the limitation of our retrospective study, it is worth considering CRT approach for patients with advanced and metastatic NSCLC - not suitable for radical treatment - who have not progressed on chemotherapy.

  20. 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.

  1. Understanding the Racial and Ethnic Differences in Cost and Mortality Among Advanced Stage Prostate Cancer Patients (STROBE).

    Science.gov (United States)

    Chhatre, Sumedha; Bruce Malkowicz, Stanley; Sanford Schwartz, J; Jayadevappa, Ravishankar

    2015-08-01

    The aims of the study were to understand the racial/ethnic differences in cost of care and mortality in Medicare elderly with advanced stage prostate cancer.This retrospective, observational study used SEER-Medicare data. Cohort consisted of 10,509 men aged 66 or older and diagnosed with advanced-stage prostate cancer between 2001and 2004. The cohort was followed retrospectively up to 2009. Racial/ethnic variation in cost was analyzed using 2 part-models and quantile regression. Step-wise GLM log-link and Cox regression was used to study the association between race/ethnicity and cost and mortality. Propensity score approach was used to minimize selection bias.Pattern of cost and mortality varies between racial/ethnic groups. Compared with other racial/ethnic groups, non-Hispanic white patients had higher unadjusted costs in treatment and follow-up phases. Quintile regression results indicated that in treatment phase, Hispanics had higher costs in the 95th quantile and non-Hispanic blacks had lower cost in the 95th quantile, compared with non-Hispanic white men. In terminal phase non-Hispanic blacks and Hispanics had higher cost. After controlling for treatment, all-cause and prostate cancer-specific mortality was not significant for non-Hispanic black men, compared with non-Hispanic white men. However, for Asians, mortality remained significantly lower compared with non-Hispanic white men.In conclusion, relationship between race/ethnicity, cost of care, and mortality is intricate. For non-Hispanic black men, disparity in mortality can be attributed to treatment differences. To reduce racial/ethnic disparities in prostate cancer care and outcomes, tailored policies to address underuse, overuse, and misuse of treatment and health services are necessary. PMID:26266389

  2. 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

  3. Phase II trial of docetaxel, cisplatin and 5FU chemotherapy in locally advanced and metastatic penis cancer (CRUK/09/001)

    OpenAIRE

    Nicholson, S.; Hall, E.; Harland, S. J.; Chester, J D; Pickering, L.; Barber, J.; Elliott, T; Thomson, A.; Burnett, S.; Cruickshank, C; Carrington, B.; Waters, R.; Bahl, A

    2013-01-01

    Background: Penis cancer is rare and clinical trial evidence on which to base treatment decisions is limited. Case reports suggest that the combination of docetaxel, cisplatin and 5-flurouracil (TPF) is highly active in this disease. Methods: Twenty-nine patients with locally advanced or metastatic squamous carcinoma of the penis were recruited into a single-arm phase II trial from nine UK centres. Up to three cycles of chemotherapy were received (docetaxel 75 mg m−2 day 1, cisplatin 60 mg m−...

  4. Anti-Angiogenic Drugs in the Treatment of Metastatic Renal Cell Carcinoma:Advances in Clinical Application

    DEFF Research Database (Denmark)

    Nielsen, Ole H; Grimm, Daniela; Wehland, Markus;

    2014-01-01

    The current paradigm in attempting to treat metastatic renal cell carcinoma (mRCC) is a first line treatment with a vascular endothelial growth factor (VEGF) antagonist and second and subsequent treatments with either a vascular endothelial growth factor receptor (VEGFR) or a mTOR (mammalian Targ...

  5. The feasibility and safety of high-intensity focused ultrasound combined with low-dose external beam radiotherapy as supplemental therapy for advanced prostate cancer following hormonal therapy

    OpenAIRE

    Wu, Rui-Yi; Wang, Guo-Min; Xu, Lei; ZHANG, BO-HENG; Xu, Ye-Qing; Zeng, Zhao-Chong; Chen, Bing

    2011-01-01

    The aim of this study was to investigate the feasibility and safety of high-intensity focused ultrasound (HIFU) combined with (+) low-dose external beam radiotherapy (LRT) as supplemental therapy for advanced prostate cancer (PCa) following hormonal therapy (HT). Our definition of HIFU+LRT refers to treating primary tumour lesions with HIFU in place of reduced field boost irradiation to the prostate, while retaining four-field box irradiation to the pelvis in conventional-dose external beam r...

  6. Six-month leuprorelin acetate depot formulations in advanced prostate cancer: a clinical evaluation

    OpenAIRE

    Tunn UW; Gruca D; Bacher P

    2013-01-01

    Ulf W Tunn,1 Damian Gruca,2 Peter Bacher3 1Urological Department, Prostate Center, Offenbach, Germany; 2AbbVie Deutschland GmbH and Co, KG, Ludwigshafen, Germany; 3AbbVie, North Chicago, IL, USA Abstract: For nearly three decades, gonadotropin-releasing hormone (GnRH) agonists, particularly leuprorelin acetate (LA), have served as an important part of the treatment armamentarium for prostate cancer. The introduction of LA depot formulations provided a significant improvement in the acceptanc...

  7. 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.

  8. 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.

  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. 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.

  11. 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.

  12. 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

    2014-11-01

    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.

  13. Is there room for combined modality treatments? Dosimetric comparison of boost strategies for advanced head and neck and prostate cancer

    OpenAIRE

    Góra, Joanna; Hopfgartner, Johannes; Kuess, Peter; Paskeviciute, Brigita; Georg, Dietmar

    2013-01-01

    The purpose of the study was to determine the dosimetric difference between three emerging treatment modalities—volumetric-modulated arc therapy (VMAT), intensity-modulated proton beam therapy (IMPT) and intensity-modulated carbon ion beam therapy (IMIT)—for two tumour sites where selective boosting of the tumour is applied. For 10 patients with locally advanced head and neck (H&N) cancer and 10 with high-risk prostate cancer (PC) a VMAT plan was generated for PTVinitial that included lymph n...

  14. Adjuvant hormone therapy in patients undergoing high-intensity focused ultrasound therapy for locally advanced prostate cancer

    OpenAIRE

    A. I. Neimark; M. A. Tachalov; B. A. Neimark

    2014-01-01

    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 = ...

  15. Recent advances in technologies for the detection of occult metastatic cells in bone marrow of breast cancer patients

    International Nuclear Information System (INIS)

    Approximately half of breast cancer patients with stage I–III disease will suffer metastatic disease despite resection with tumour-free margins. In 30–40% of these patients, individual carcinoma cells can already be detected at the time of primary therapy in cytological bone marrow preparations using immunocytochemistry. Numerous prospective clinical studies have shown that the presence of occult metastatic cells in bone marrow is prognostically relevant to patient survival. Only a few studies failed to do so, thus stimulating a critical discussion on the methodology and clinical value of bone marrow analysis. The potential for obtaining improved prognostic information on patient outcome, for monitoring tumour cell eradication during adjuvant and palliative systemic therapy, and for specifically targeting tumour biological therapies are intriguing clinical opportunities that may be afforded by bone marrow analysis. Standardized and robust methodology is a prerequisite for clinical application of these techniques, however

  16. 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.)

  17. 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.)

  18. A phase 2 study of high-activity 186Re-HEDP with autologous peripheral blood stem cell transplant in progressive hormone-refractory prostate cancer metastatic to bone

    International Nuclear Information System (INIS)

    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 186Re-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 186Re-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 186Re-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.)

  19. Phase II study of safety and efficacy of motesanib in patients with progressive or symptomatic, advanced or metastatic medullary thyroid cancer

    DEFF Research Database (Denmark)

    Schlumberger, Martin J; Elisei, Rossella; Bastholt, Lars;

    2009-01-01

    PURPOSE: This phase II study investigated the efficacy and tolerability of motesanib, an investigational, highly selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3; platelet-derived growth factor receptor; and Kit in advanced medullary thyroid cancer (MTC). PATIENTS AND...... METHODS: Patients with locally advanced or metastatic, progressive or symptomatic MTC received motesanib 125 mg/d orally for up to 48 weeks or until unacceptable toxicity or disease progression. The primary end point was objective response by independent review. Other end points included duration of...... response, progression-free survival, safety, pharmacokinetics, and changes in tumor markers. RESULTS: Of 91 enrolled patients who received motesanib, two (2%) achieved objective response (95% CI, 0.3% to 7.7%); their duration of response was 32 weeks (censored) and 21 weeks (disease progressed). Eighty...

  20. 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....

  1. Economic analysis of a phase III clinical trial evaluating the addition of total androgen suppression to radiation versus radiation alone for locally advanced prostate cancer (Radiation Therapy Oncology Group protocol 86-10)

    International Nuclear Information System (INIS)

    Purpose: To evaluate the cost-effectiveness of adding hormone therapy to radiation for patients with locally advanced prostate cancer, using a Monte Carlo simulation of a Markov Model. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 86-10 randomized patients to receive radiation therapy (RT) alone or RT plus total androgen suppression (RTHormones) 2 months before and during RT for the treatment of locally advanced prostate cancer. A Markov model was designed with Data Pro (TreeAge Software, Williamstown, MA). The analysis took a payer's perspective. Transition probabilities from one state of health (i.e., with no disease progression or with hormone-responsive metastatic disease) to another were calculated from published rates pertaining to RTOG 86-10. Patients remained in one state of health for 1 year. Utility values for each health state and treatment were obtained from the literature. Distributions were sampled at random from the treatment utilities according to a second-order Monte Carlo simulation technique. Results: The mean expected cost for the RT-only treatments was $29,240 (range, $29,138-$29,403). The mean effectiveness for the RT-only treatment was 5.48 quality-adjusted life years (QALYs) (range, 5.47-5.50). The mean expected cost for RTHormones was $31,286 (range, $31,058-$31,555). The mean effectiveness was 6.43 QALYs (range, 6.42-6.44). Incremental cost-effectiveness analysis showed RTHormones to be within the range of cost-effectiveness at $2,153/QALY. Cost-effectiveness acceptability curve analysis resulted in a >80% probability that RTHormones is cost-effective. Conclusions: Our analysis shows that adding hormonal treatment to RT improves health outcomes at a cost that is within the acceptable cost-effectiveness range

  2. Advances in bi-modal optical and ultrasound detection of prostate cancer diagnosis

    Science.gov (United States)

    Boutet, Jerome; Guyon, Laurent; Debourdeau, Mathieu; Dinten, Jean-Marc; Vray, Didier; Rizo, Philippe

    2009-02-01

    Prostate cancer diagnosis is based on PSA dosage and digital rectal examination. In case of positive test, a biopsy is conducted and guided by ultrasound imaging. Today, however, as ultrasound imaging is not able to precisely detect tumors, some biopsies have to be performed in the prostate and the only way to improve detection is to increase the number of those uncomfortable biopsies. In order to decrease this number and to improve the patient wellness, we are studying a way to couple ultrasound and fluorescence optical imaging on an endorectal probe. The ultrasounds are used to get morphological information on the prostate and the optical system to detect and to localize fluorophore marked tumors. To support the development of such a system, we have carried out a new tissue-mimicking phantom which represents the three different kind of tissue concerned during prostate endorectal examination: prostate, rectum, surrounding tissues. It was imaged by ultrasound and by fluorescence diffuse optical imaging. We have proved that the optical system is able to detect and to localize a fluorescing inclusion at different depth inside the phantom which has then been superimposed to the morphological image provided by the ultrasounds.

  3. [New challenges and earlier approved methods in the laboratory diagnosis of prostate cancer].

    Science.gov (United States)

    Kovács, Gábor L

    2014-12-01

    Prostate cancer is usually a disease of elderly men, however, over 40 years of age the tumor can appear at any times. PSA is a protein molecule synthesized by prostate cells. Measurement of serum PSA has revolutionized the diagnosis and treatment of prostate cancer. However, PSA is not sufficiently specific for the detection of prostate cancer, since serum PSA might also be elevated in benign prostate diseases, as well as following physical stimulation of the gland (digital rectal examination, biopsy, catheterization, or even ejaculation). To increase the specificity of PSA, different derivative parameters have been developed i.e. PSA density (ratio of PSA to prostate volume), PSA velocity (change of PSA over a time period) or age-specific reference ranges. 65-95% of circulating PSA is bound to different proteins, while the rest of PSA circulates in a non-bound form (free PSA, fPSA). In addition to fPSA, the prostate health index [phi; (-2)proPSA/fPSA×√PSA] is increasingly used to differentiate between carcinoma-induced and non-carcinoma-induced increase in PSA. PCA3 is a non-coding messenger RNA, which is 60-70-fold overexpressed by cancer cells in the prostate. Measurement of urine PCA3 appears to be more sensitive than %tPSA, and is independent of prostate volume, age or tPSA. The author reviews laboratory biomarkers related to prostate cancer, used either in the routine clinical practice, or in research. Laboratory biomarkers seem to be useful tools to reduce the incidence of advanced stage, or metastatic prostate cancer, and the cancer-related death rate. A promising perspective for the future is the detection of circulating prostate cancer cells and the profiling of microRNAs, especially on the field of tumor prognosis. PMID:25517448

  4. 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.

  5. Carmustine enhances the anticancer activity of selenite in androgen-independent prostate cancer cells

    International Nuclear Information System (INIS)

    Apoptosis is one of the major mechanisms targeted in the development of therapies against various cancers, including prostate cancer. Resistance to chemotherapy poses a significant problem for the effective treatment of androgen-independent (hormone-refractory) prostate cancer. Although high concentrations of sodium selenite exert strong anticarcinogenic effects in several cell culture systems and animal models, the therapeutic potential of selenite in patients with advanced or metastatic prostate cancer is extremely limited by the genotoxicity of high-dose selenite. We examined the ability of nontoxic concentrations of selenite to promote apoptosis and inhibit proliferation in carmustine-sensitized androgen-independent human prostate cancer cells. Androgen-dependent LNCaP cells exhibited a significant decrease in cell viability when exposed to nontoxic concentrations of selenite, whereas androgen-independent PC-3 and DU145 cells showed a significant decrease in cell viability only at higher concentrations. Treatment of PC-3 cells with a combination of nontoxic selenite and carmustine resulted in greater increases in cytotoxicity, reactive oxygen species generation, growth inhibition, apoptosis, and DNA double-strand breaks, with concomitant decreases in DNA synthesis, glutathione, glutathione reductase, and antiapoptotic proteins. Combination treatment with carmustine and selenite triggered caspase-dependent apoptosis in PC-3 cells, which was not apparent when these cells were treated with selenite or carmustine alone. Genotoxicity in normal prostate epithelial cells was completely absent in the combination treatment of carmustine and selenite. In addition, carmustine decreased the induction of DNA double strand breaks by high-dose selenite in normal prostate epithelial cells. This is the first study to demonstrate that a nontoxic dose of selenite, in combination with carmustine, significantly induces apoptosis and growth inhibition in androgen

  6. Potassium channels in prostate and colonic cancer

    OpenAIRE

    Ousingsawat, Jiraporn

    2007-01-01

    Large conductance Ca2+-activated K+ channels in human prostate cancer The KCNMA1 gene encoding the alpha-subunit of BK channels is amplified and BK channel expression is enhanced in late-stage, metastatic and hormone-refractory human prostate cancer tissues, whereas benign prostate tissues show only a weak expression of BK channels. PC-3 hormone-insensitive prostate cancer cells, but not hormone-sensitive prostate cancer cells (LNCaP) and benign prostate hyperplasia cells (BPH-1), show an ...

  7. 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.)

  8. Metastatic Cancer

    Science.gov (United States)

    ... Breast Bone, brain, liver, lung Colorectal Liver, lung, peritoneum Kidney Adrenal gland , bone, brain, liver, lung Lung ... brain, liver, lung, skin/muscle Ovary Liver, lung, peritoneum Pancreas Liver, lung, peritoneum Prostate Adrenal gland, bone, ...

  9. 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

    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...

  10. Looking beyond Androgen Receptor Signaling in the Treatment of Advanced Prostate Cancer

    Directory of Open Access Journals (Sweden)

    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.

  11. 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...

  12. A phase II trial of the BCL-2 homolog domain 3 mimetic AT-101 in combination with docetaxel for recurrent, locally advanced, or metastatic head and neck cancer

    Science.gov (United States)

    Swiecicki, Paul L.; Bellile, Emily; Sacco, Assuntina G.; Pearson, Alexander T.; Taylor, Jeremy M. G.; Jackson, Trachette L.; Chepeha, Douglas B.; Spector, Matthew E.; Shuman, Andrew; Malloy, Kelly; Moyer, Jeffrey; McKean, Erin; McLean, Scott; Sukari, Ammar; Wolf, Gregory T.; Eisbruch, Avraham; Prince, Mark; Bradford, Carol; Carey, Thomas E.; Wang, Shaomeng; Nör, Jacques E.; Worden, Francis P.

    2016-01-01

    Background AT-101 is a BCL-2 Homolog domain 3 mimetic previously demonstrated to have tumoricidal effects in advanced solid organ malignancies. Given the evidence of activity in xenograft models, treatment with AT-101 in combination with docetaxel is a therapeutic doublet of interest in metastatic head and neck squamous cell carcinoma. Patients and Methods Patients included in this trial had unresectable, recurrent, or distantly metastatic head and neck squamous cell carcinoma (R/M HNSCC) not amenable to curative radiation or surgery. This was an open label randomized, phase II trial in which patients were administered AT-101 in addition to docetaxel. The three treatment arms were docetaxel, docetaxel plus pulse dose AT-101, and docetaxel plus metronomic dose AT-101. The primary endpoint of this trial was overall response rate. Results Thirty-five patients were registered and 32 were evaluable for treatment response. Doublet therapy with AT-101 and docetaxel was well tolerated with only 2 patients discontinuing therapy due to treatment related toxicities. The overall response rate was 11% (4 partial responses) with a clinical benefit rate of 74%. Median progression free survival was 4.3 months (range: 0.7–13.7) and overall survival was 5.5 months (range: 0.4–24). No significant differences were noted between dosing strategies. Conclusion Although met with a favorable toxicity profile, the addition of AT-101 to docetaxel in R/M HNSCC does not appear to demonstrate evidence of efficacy. PMID:27225873

  13. C-reactive protein in patients with advanced metastatic renal cell carcinoma: Usefulness in identifying patients most likely to benefit from initial nephrectomy

    International Nuclear Information System (INIS)

    C-reactive protein (CRP) is considered a useful serum marker for patients with RCC. However, its clinical utility in advanced metastatic renal cell carcinoma (AM-RCC), particularly in deciding whether to perform nephrectomy at the onset, is not well studied. We retrospectively evaluated 181 patients with AM-RCC, including 18 patients underwent potentially curative surgery, 111 underwent cytoreductive nephrectomy, and 52 received medical treatment only. CRP cutoff points were determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier and Cox regression analyses were used for survival tests. ROC analysis suggested that grouping patients according to 3 CRP ranges was a rational model. Patients with highly elevated CRP (≥67.0 mg/L) presented remarkably poor prognosis despite treatment (nephrectomy or medical treatment only). Cox regression models demonstrated that risk factors of overall survival for patients who underwent nephrectomy were the CRP ranges defined in this study (≤18.0 mg/L, >18.0 and <67.0 mg/L, and ≥67.0 mg/L), ECOG PS (0, 1, and ≥2), and number of metastatic organ sites (0–1 and ≥2). The retrospective design is a limitation of this study. Our study demonstrated that the serum CRP level is a statistically significant prognostic parameter for patients with AM-RCC. The data also indicated that pretreatment serum CRP level provides useful prognostic information that helps in deciding whether to perform initial nephrectomy for patients with AM-RCC

  14. Radium-223-Dichloride in Castration Resistant Metastatic Prostate Cancer—Preliminary Results of the Response Evaluation Using F-18-Fluoride PET/CT

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

    Directory of Open Access Journals (Sweden)

    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

  16. Favorable outcomes in locally advanced and node positive prostate cancer patients treated with combined pelvic IMRT and androgen deprivation therapy

    International Nuclear Information System (INIS)

    The most appropriate treatment for men with prostate cancer and positive pelvic nodes, N+, is an area of active controversy. We report our 5-years outcomes in men with locally advanced prostate cancer (T1-T4N0-N1M0) treated with definitive radiotherapy encompassing the prostate and pelvic lymph nodes (intensity modulated radiotherapy, IMRT) and long-term androgen deprivation therapy (ADT). Of the 138 consecutive eligible men all living patients have been followed up to almost 5 years. Survival endpoints for 5-year biochemical failure-free survival (BFFS), relapse-free survival (RFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were assessed by Kaplan-Meier analysis. Univariate and multivariate Cox regression proportional hazards models were constructed for all survival endpoints. The RTOG morbidity grading system for physician rated toxicity was applied. Patients with locally advanced T3-T4 tumors (35 %) and N1 (51 %) have favorable outcome when long-term ADT is combined with definitive radiotherapy encompassing pelvic lymph nodes. The 5-year BFFS, RFS, PCSS and OS were 71.4, 76.2, 94.5 and 89.0 %, respectively. High Gleason sum (9–10) had a strong independent prognostic impact on BFFS, RFS and OS (p = 0.001, <0.001, and 0.005 respectively). The duration of ADT (= > 28 months) showed a significant independent association with improved PCSS (p = 0.02) and OS (p = 0.001). Lymph node involvement was not associated with survival endpoints in the multivariate analysis. The radiotherapy induced toxicity seen in our study population was moderate with rare Grade 3 GI side effects and up to 11 % for Grade 3 GU consisting mainly of urgency and frequency. Pelvic IMRT in combination with long-term ADT can achieve long-lasting disease control in men with N+ disease and unfavorable prognostic factors. The online version of this article (doi:10.1186/s13014-015-0540-3) contains supplementary material, which is available to authorized users

  17. 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.

  18. Regulation of prostate cancer progression by the tumor microenvironment.

    Science.gov (United States)

    Shiao, Stephen L; Chu, Gina Chia-Yi; Chung, Leland W K

    2016-09-28

    Prostate cancer remains the most frequently diagnosed cancer in men in North America, and despite recent advances in treatment patients with metastatic disease continue to have poor five-year survival rates. Recent studies in prostate cancer have revealed the critical role of the tumor microenvironment in the initiation and progression to advanced disease. Experimental data have uncovered a reciprocal relationship between the cells in the microenvironment and malignant tumor cells in which early changes in normal tissue microenvironment can promote tumorigenesis and in turn tumor cells can promote further pro-tumor changes in the microenvironment. In the tumor microenvironment, the presence of persistent immune infiltrates contributes to the recruitment and reprogramming of other non-immune stromal cells including cancer-associated fibroblasts and a unique recently identified population of metastasis-initiating cells (MICs). These MICs, which can also be found as part of the circulating tumor cell (CTC) population in PC patients, promote cancer cell transformation, enhance metastatic potential and confer therapeutic resistance. MICs act can on other cells within the tumor microenvironment in part by secreting exosomes that reprogram adjacent stromal cells to create a more favorable tumor microenvironment to support continued cancer growth and progression. We review here the current data on the intricate relationship between inflammation, reactive stroma, tumor cells and disease progression in prostate cancer. PMID:26828013

  19. 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.

  20. 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

    -resistant prostate cancer. Overall survival (OS) and radiographic progression-free survival (rPFS) were coprimary end points. Subgroup analysis of men aged ≥75 years (elderly) and men aged ... 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....

  1. By inhibiting snail signaling and miR-23a-3p, osthole suppresses the EMT-mediated metastatic ability in prostate cancer.

    Science.gov (United States)

    Wen, Yu-Ching; Lee, Wei-Jiunn; Tan, Peng; Yang, Shun-Fa; Hsiao, Michael; Lee, Liang-Ming; Chien, Ming-Hsien

    2015-08-28

    Here we showed that Osthole, 7-methoxy-8-(3-methyl-2-butenyl) coumarin, a bioactive coumarin derivative extracted from medicinal plants, inhibited migration, invasion, epithelial to mesenchymal transition (EMT) in androgen-independent prostate cancer (AIPC) cells in vitro and metastasis of AIPC in vivo. In patients, high Snail levels were correlated with a higher histological Gleason sum and poor survival rates. Osthole inhibited the TGF-β/Akt/MAPK pathways, reduced Snail-DNA-binding activity and induced E-cadherin. We found that osthole decreased miR-23a-3p. Ectopic miR-23a-3p suppressed E-cadherin 3' untranslated region reporter activity and E-cadherin expression, and relieved the motility suppression caused by osthole treatment. PMID:26110567

  2. 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

    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......Myeloid-derived suppressor cells (MDSC) are believed to play a role in immune suppression and subsequent failure of T cells to mount an efficient anti-tumor response, by employing both direct T-cell inhibition as well as induction of regulatory T cells (Tregs). Investigating the frequency and...... correlated positively with Treg levels. In vitro proliferation assay with autologous T cells confirmed M-MDSC-mediated T-cell suppression, and intracellular staining of immune suppressive enzyme iNOS revealed a higher expression in M-MDSC from patients with PC. Increased frequencies of M-MDSC correlated with...

  3. 3'-Deoxy-3'-18F-fluorothymidine positron emission tomography as an early predictor of disease progression in patients with advanced and metastatic pancreatic cancer

    International Nuclear Information System (INIS)

    3'-Deoxy-3'-18F-fluorothymidine (FLT) positron emission tomography (PET) has limited utility in abdominal imaging due to high physiological hepatic uptake of tracer. We evaluated FLT PET/CT combined with a temporal-intensity information-based voxel-clustering approach termed kinetic spatial filtering (FLT PET/CTKSF) for early prediction of response and survival outcomes in locally advanced and metastatic pancreatic cancer patients receiving gemcitabine-based chemotherapy. Dynamic FLT PET/CT data were collected before and 3 weeks after the first cycle of chemotherapy. Changes in tumour FLT PET/CT variables were determined. The primary end point was RECIST 1.1 response on contrast-enhanced CT after 3 months of therapy. Twenty patients were included. Visual distinction between tumours and normal pancreas was seen in FLT PETKSF images. All target lesions (>2 cm), including all primary pancreatic tumours, were visualised. Of the 11 liver metastases, 3 (<2 cm) were not visible after kinetic filtering. Of the 20 patients, 7 progressed (35 %). Maximum standardised uptake value at 60 min post-injection (SUV60,max) significantly increased in patients with disease progression (p = 0.04). Receiver-operating characteristic curve analysis indicated that a threshold of SUV60,max increase of ≥ 12 % resulted in sensitivity, specificity and positive predictive value (PPV) of 71, 100 and 100 %, respectively [area under the curve (AUC) 0.90, p = 0.0001], to predict patients with disease progression. Changes in SUV60,max were not predictive of survival. FLT PET/CT detected changes in proliferation, with early increase in SUV60,max predicting progressive disease with a high specificity and PPV. Therefore, FLT PET/CT could be used as an early response biomarker for gemcitabine-based chemotherapy, to select a poor prognostic group who may benefit from novel therapeutic agents in advanced and metastatic pancreatic cancer. (orig.)

  4. 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. PMID:17382431

  5. Feasibility study of DCs/CIKs combined with thoracic radiotherapy for patients with locally advanced or metastatic non-small-cell lung cancer

    International Nuclear Information System (INIS)

    The combination of dendritic cells (DCs) and cytokine-induced killer cells (CIKs) can induce the anti-tumor immune response and radiotherapy may promote the activity. We aimed to explore the feasibility of DCs/CIKs combined with thoracic radiotherapy (TRT) for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). In this study, patients with unresectable stage III/IV NSCLC and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0–2 and previously receiving two or more cycles of platinum-based doublet chemotherapy without disease progression received TRT plus DCs/CIKs or TRT alone until disease progression or unacceptable toxicity. The primary endpoint was median progression-free survival (mPFS). In treatment group, patients received four-cycle autologous DCs/CIKs infusion starting from the 6th fraction of irradiation. From Jan 13, 2012 to June 30, 2014, 82 patients were enrolled, with 21 patients in treatment group and 61 in control group. The mPFS in treatment group was longer than that in control group (330 days vs 233 days, hazard ratio 0.51, 95 % CI 0.27–1.0, P < 0.05), and the objective response rate (ORR) of treatment group (47.6 %) was significantly higher that of control group (24.6 %, P < 0.05). There was no significant difference in disease control rate (DCR) and median overall survival (mOS) between two groups (P > 0.05). The side effects in treatment group were mild and there was no treatment-related deaths. The combination of DCs/CIKs with TRT could be a feasible regimen in treating locally advanced or metastatic NSCLC patients. Further investigation of the regimen is warranted

  6. 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.

    2016-01-01

    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. PMID:26675257

  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. Treatment characteristics and mortality of a large insured female population with advanced or metastatic breast cancer by receipt of HER2-targeted agents

    Directory of Open Access Journals (Sweden)

    Hao Y

    2015-04-01

    Full Text Available Yanni Hao,1 Nicole Meyer,2 Pamela Landsman-Blumberg,2 William Johnson,2 Jaqueline Willemann Rogerio1 1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 2Truven Health Analytics, Cambridge, MA, USA Purpose: This retrospective administrative claims study of women diagnosed with advanced or metastatic breast cancer compared treatment characteristics and mortality by receipt of human epithelial growth factor receptor 2 (HER2-targeted agents and by disease stage and age group among patients using HER2-targeted agents. Patients and methods: Adult women diagnosed with stage III or IV breast cancer (index date between 2008 and 2012 were identified from MarketScan® databases containing medical and pharmacy claims for >40 million enrollees insured with >100 US health plans. Patients were followed until the earlier of the following: end of enrollment, inpatient death, or December 31, 2012. Study cohorts were women ± HER2-targeted agent use, HER2-targeted agent users' subgroups of stages III and IV, and age group. Pre- and postindex breast cancer treatments were compared among study cohorts. Overall survival was compared using log-rank tests. Cox proportional-hazards models were used to study the predictors of overall survival. Results: Of 30,660 eligible women, 14.4% received HER2-targeted agents. HER2-targeted agent users received more aggressive pre- and postindex cancer treatments compared to those with no HER2-targeted agents. HER2-targeted agents had higher rates of pre- and postindex breast cancer surgery, adjuvant/neoadjuvant chemotherapy, radiation therapy, chemotherapy, and biologics-based therapy. Among HER2-targeted agent users, younger women and those with stage III breast cancer received more aggressive treatments. After adjusting for clinically relevant patient characteristics, women receiving HER2-targeted agents had a 20% reduced risk of death compared to patients not receiving HER2-targeted agents. Among all patients and the

  9. 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

  10. Maintenance Therapy Containing Metformin and/or Zyflamend for Advanced Prostate Cancer: A Case Series

    OpenAIRE

    Mehmet Asim Bilen; Sue-Hwa Lin; Tang, Dean G.; Kinjal Parikh; Mong-Hong Lee; Yeung, Sai-Ching J; Shi-Ming Tu

    2015-01-01

    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 Zy...

  11. AB084. Docetaxel therapy for hormone-sensitive prostate cancer—single center result

    OpenAIRE

    Shao, Qiang; Du, Yuan; Zhang, Fengbo; Tian, Ye

    2015-01-01

    Background Androgen-deprivation therapy (ADT) has been the treatment for metastatic prostate cancer for more 75 years. We assessed whether concomitant treatment with ADT added to docetaxel would result in patients newly-diagnosed metastatic hormone-sensitive prostate cancer for longer overall survival. Methods and Materials Since August 2014, 14 patients with metastatic, hormone-sensitive prostate cancer received ADT plus docetaxel (at a dose of 75 mg per square meter of body-surface area eve...

  12. Long-Term Follow-Up of HLA-A2+ Patients with High-Risk, Hormone-Sensitive Prostate Cancer Vaccinated with the Prostate Specific Antigen Peptide Homologue (PSA146-154)

    OpenAIRE

    Perambakam, Supriya; Xie, Hui; Edassery, Seby; Peace, David J.

    2011-01-01

    Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum...

  13. Long-Term Follow-Up of HLA-A2+ Patients with High-Risk, Hormone-Sensitive Prostate Cancer Vaccinated with the Prostate Specific Antigen Peptide Homologue (PSA146-154)

    OpenAIRE

    Perambakam, Supriya; Xie, Hui; Edassery, Seby; Peace, David J.

    2010-01-01

    Twenty-eight HLA-A2+ patients with high-risk, locally advanced or metastatic, hormone-sensitive prostate cancer were immunized with a peptide homologue of prostate-specific antigen, PSA146-154, between July 2002 and September 2004 and monitored for clinical and immune responses. Fifty percent of the patients developed strong PSA146-154-peptide-specific delayed-type hypersensitivity skin responses, tetramer and/or IFN-γ responses within one year. Thirteen patients had stable or declining serum...

  14. Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

    OpenAIRE

    MOMOZONO, HIROYUKI; Miyake, Hideaki; TEI, HIROMOTO; Harada, Ken-ichi; Fujisawa, Masato

    2016-01-01

    The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With...

  15. 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

  16. Effects on quality of life of weekly docetaxel-based chemotherapy in patients with locally advanced or metastatic breast cancer: results of a single-centre randomized phase 3 trial

    Directory of Open Access Journals (Sweden)

    Rinaldo Massimo

    2011-02-01

    Full Text Available Abstract Background To evaluate whether weekly schedules of docetaxel-based chemotherapy were superior to 3-weekly ones in terms of quality of life in locally advanced or metastatic breast cancer. Methods Patients with locally advanced or metastatic breast cancer, aged ≤ 70 years, performance status 0-2, chemotherapy-naive for metastatic disease, were eligible. They were randomized to weekly or 3-weekly combination of docetaxel and epirubicin, if they were not treated with adjuvant anthracyclines, or docetaxel and capecitabine, if treated with adjuvant anthracyclines. Primary end-point was global quality of life change at 6-weeks, measured by EORTC QLQ-C30. With two-sided alpha 0.05 and 80% power for 35% effect size, 130 patients per arm were needed. Results From February 2004 to March 2008, 139 patients were randomized, 70 to weekly and 69 to 3-weekly arm; 129 and 89 patients filled baseline and 6-week questionnaires, respectively. Global quality of life was better in the 3-weekly arm (p = 0.03; patients treated with weekly schedules presented a significantly worsening in role functioning and financial scores (p = 0.02 and p Conclusions In this trial, the weekly schedules of docetaxel-based chemotherapy appear to be inferior to the 3-weekly one in terms of quality of life in patients with locally advanced or metastatic breast cancer. Trial registration ClinicalTrials.gov NCT00540800.

  17. 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.

  18. A randomized non-comparative phase II trial of cixutumumab (IMC-A12) or ramucirumab (IMC-1121B) plus mitoxantrone and prednisone in men with metastatic docetaxel-pretreated castration-resistant prostate cancer

    Science.gov (United States)

    Hussain, Maha; Rathkopf, Dana; Liu, Glenn; Armstrong, Andrew; Kelly, Wm. Kevin; Ferrari, Anna; Hainsworth, John; Joshi, Adarsh; Hozak, Rebecca R.; Yang, Ling; Schwartz, Jonathan D.; Higano, Celestia S.

    2016-01-01

    Background Cixutumumab, a human monoclonal antibody (HuMAb), targets the insulin-like growth factor receptor. Ramucirumab is a recombinant HuMAb that binds to vascular endothelial growth factor receptor-2. A non-comparative randomized phase II study evaluated cixutumumab or ramucirumab plus mitoxantrone and prednisone (MP) in metastatic castration-resistant prostate cancer (mCRPC). Patients and Methods Men with progressive mCRPC during or after docetaxel therapy received mitoxantrone 12 mg/m2 on day 1 and prednisone 5 mg twice daily and were randomized 1:1 to receive either cixutumumab or ramucirumab 6 mg/kg intravenously weekly in a 21-day cycle. Primary endpoint was composite progression-free survival (cPFS). Secondary endpoints included safety, response, radiographic PFS, and overall survival (OS). Sample size was based on a 50% increase in median cPFS from 2.6 (MP) to 3.9 months (either combination). Results 132 men were treated (66 per arm). Median cPFS was 4.1 months (95% CI, 2.2–5.6) for cixutumumab and 6.7 months (95% CI, 4.5–8.3) for ramucirumab. Median time to radiographic progression was 7.5 months for cixutumumab and 10.2 months for ramucirumab, with a median OS of 10.8 and 13.0 months, respectively. Fatigue was the most frequent adverse event (AE). Incidence of most non-hematologic grade 3-4 AEs was <10% on both arms. Grade 3 cardiac dysfunction occurred in 7.6% of patients on ramucirumab. Conclusion Combinations of cixutumumab or ramucirumab plus MP were feasible and associated with moderate toxicities in docetaxel pretreated men with mCRPC. Of the two regimens, the ramucirumab regimen is worthy of further testing based on the observed cPFS relative to the historical control. PMID:26082390

  19. A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899

    Directory of Open Access Journals (Sweden)

    Carducci Michael

    2010-02-01

    Full Text Available Abstract Background To test the hypothesis that modulation of Bcl-2 with 13-cis retinoic acid (CRA/interferon-alpha2b (IFN with paclitaxel (TAX, or mitoxantrone, estramustine and vinorelbine (MEV will have clinical activity in men with metastatic castrate-resistant prostate cancer (CRPC. Methods 70 patients were treated with either MEV (Arm A in a 3-week cycle or CRA/IFN/TAX with an 8-week cycle (Arm B. Patients were assessed for response, toxicity, quality of life (QOL, and the effect of treatment on Bcl-2 levels in peripheral blood mononuclear cells (PBMC. Results The PSA response rates were 50% and 23%, measurable disease response rates (CR+PR 14% and 15%, and median overall survival 19.4 months and 13.9 months on Arm A and Arm B respectively. Transient grade 4 neutropenia occurred in 18 and 2 patients, and grade 3 to 4 thrombosis in 7 patients and 1 patient in Arm A and Arm B respectively. Patients on Arm B reported a clinically significant decline in QOL between baseline and week 9/10 (.71 s.d., and a significantly lower level of QOL than Arm A (p = 0.01. As hypothesized, Bcl-2 levels decreased with CRA/IFN therapy only in Arm B (p = 0.03. Conclusions Treatment with MEV was well tolerated and demonstrated clinical activity in patients with CRPC. Given the adverse effect of CRA/IFN/TAX on QOL, the study of other novel agents that target Bcl-2 family proteins is warranted. The feasibility of measuring Bcl-2 protein in a cooperative group setting is hypothesis generating and supports further study as a marker for Bcl-2 targeted therapy. Trial Registration Clinical Trials Registration number: CDR0000067865

  20. Dosing considerations for capecitabine-irinotecan regimens in the treatment of metastatic and/or locally advanced colorectal cancer.

    Science.gov (United States)

    Cartwright, Thomas; McCollum, David; Boehm, Kristi A

    2010-06-01

    Capecitabine (Xeloda), Roche Laboratories Inc., Nutley, NJ) is an orally administered fluoropyrimidine carbamate that serves as a prodrug of 5-fluorouracil (5-FU), an integral component of chemotherapy (CT) regimens for metastatic colorectal cancer (mCRC). As the drug is orally administered, capecitabine permits greater convenience and flexibility in dosing by eliminating the need for continuous infusion and its potential complications. In phase 3 trials, capecitabine has been used as an alternative to 5-FU, both as a monotherapy and in combination with agents such as oxaliplatin (as XELOX), with good efficacy and tolerability. Combination therapy with capecitabine and irinotecan (XELIRI), however, has produced more variable results, with some dose combinations and schedules resulting in excessive and/or unexplained treatment-related toxicity. Recent initiatives using lower doses of capecitabine and irinotecan, as well as alternative dosing schedules, have resulted in more favorable outcomes (efficacy and tolerability), even in combination with targeted-agents such as bevacizumab. Dose reduction in elderly populations and in those with moderate renal impairment also appears to be important for minimizing toxicity with XELIRI regimens. Although additional phase 3 studies are needed, XELIRI may be an effective base CT regimen, allowing a greater number of treatment options for tumor control in patients with mCRC.

  1. Overexpression of vimentin in canine prostatic carcinoma

    DEFF Research Database (Denmark)

    Rodrigues, M M P; Rema, A; Gärtner, F;

    2011-01-01

    is associated with the invasive phenotype of human prostate cancer cells. The aim of the present study was to characterize immunohistochemically the expression of vimentin by canine prostatic carcinomas. Primary carcinomas and metastatic tumour foci both showed vimentin expression. This finding suggests...

  2. 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.

  3. Long-term cancer-related fatigue outcomes in patients with locally advanced prostate cancer after intensity-modulated radiotherapy combined with hormonal therapy

    Science.gov (United States)

    Luo, Hua-Chun; Lei, Yong; Cheng, Hui-Hua; Fu, Zhi-Chao; Liao, Shao-Guang; Feng, Jing; Yin, Qin; Chen, Qun-Hua; Lin, Gui-Shan; Zhu, Jin-Feng; Xu, Jian-Feng; Wang, Dian

    2016-01-01

    Abstract The aim of our study was to investigate the relationship between cancer-related fatigue and clinical parameters, and the effect factors of fatigue for the prostate cancer patients. Long-term follow-up is performed using the Fatigue Symptom Inventory before treatment (A), at the end of intensity-modulated radiotherapy (B), and 3 months (C), 12 months (D), 24 months (E), 36 months (F), and 48 months (G) after the end of intensity-modulated radiotherapy. Three dimensions of fatigue are assessed during follow-up: severity, perceived interference with quality of life, and duration in the past week. In all, 97 patients with locally advanced prostate cancer were enrolled in the study. Median follow-up time was 43.9 months. The fatigue index was significantly higher in the prostate-specific antigen >20 ng/mL, Gleason score >8, the Eastern Cooperative Oncology Group scores, and the higher education. The most severe fatigue occurred at time points B and C. The score for duration of fatigue fluctuated across the time points, with significantly increased scores at time points D, E, and F. In conclusion, we show that cancer-related fatigue is the important symptom which affects the quality of life for the prostate cancer patients. For patients with locally advanced prostate cancer with a high Eastern Cooperative Oncology Group score, a Gleason score of >8 points, prostate-specific antigen levels of >20 ng/mL, and high education, attention should be paid to the interference of fatigue with quality of life, especially general level of activity, ability to concentrate, and mood, after radiotherapy combined with hormonal therapy. PMID:27336890

  4. [Reducing the side effects of aggressive chemotherapy (cisplatin and epirubicin) with xenogenic peptides (factor AF2) in patients with hormone refractory metastatic prostate cancer. A prospective, randomized study].

    Science.gov (United States)

    Papadopoulos, I; Wand, H

    1989-06-01

    The indication of a chemotherapy is advisable with patients who are suffering from a progressively metastasised, secondarily hormone refractory carcinoma of the prostate. In search of efficient chemotherapy protocols we combined cisplatin with epirubicin (PE scheme) in our clinic. Massive side effects of that aggressive chemotherapy scheme like gastro-intestinal trouble and myelotoxicity are the limiting factors of the scheme. With measures like reducing the dosage, delaying the next cycle, or breaking off the therapy the effective dosage can often not be achieved. The anti-emetics which are usually used today exclusively give anti-emetic protection. The additional administration of xenogenic peptides (Factor AF2) had additionally myeloprotective effect in former studies. In this study we examined whether, by additionally giving Factor AF2, the patients' subjective condition, and above all their hemogram, could be stabilised in order to achieve the effective dosage or dosage intensity. For that, the patients were prospectively randomised in two groups by means of a random selection board. The analysis of the data gained in the protocol showed that the additional administration of Factor AF2 improves the patients' subjective conditions significantly. Apart from that, we noticed a considerable reduction of the vomiting frequency. Concerning the objective measured parameters of the leukocytes, thrombocytes, erythrocytes, and the hemoglobin level, the significantly myeloprotective effect of Factor AF2 could be proved. Due to the fact that in the verum group there were considerably fewer cases of breaking off or delays of the treatment than in the control group, the effective dosage intensity could be achieved with a higher number of patients in that group. PMID:2691943

  5. Enlarged prostate

    Science.gov (United States)

    BPH; Benign prostatic hyperplasia (hypertrophy); Prostate - enlarged ... Lepor H. Evaluation and nonsurgical management of benign prostatic hyperplasia. In: Wein AJ, ed. Campbell-Walsh Urology . 10th ...

  6. New serum biomarkers for prostate cancer diagnosis

    OpenAIRE

    Chadha, Kailash C.; Austin Miller; Nair, Bindukumar B.; Schwartz, Stanley A.; Trump, Donald L.; Willie Underwood

    2014-01-01

    Background: Prostate-specific antigen (PSA) is currently used as a biomarker for diagnosis and management of prostate cancer (CaP). However, PSA typically lacks the sensitivity and specificity desired of a diagnostic marker. Objective: The goal of this study was to identify an additional biomarker or a panel of biomarkers that is more sensitive and specific than PSA in differentiating benign versus malignant prostate disease and/or localized CaP versus metastatic CaP. Methods: Concurrent meas...

  7. Prostate Cancer and Bone: The Elective Affinities

    OpenAIRE

    Nadia Rucci; Adriano Angelucci

    2014-01-01

    The onset of metastases dramatically changes the prognosis of prostate cancer patients, determining increased morbidity and a drastic fall in survival expectancy. Bone is a common site of metastases in few types of cancer, and it represents the most frequent metastatic site in prostate cancer. Of note, the prevalence of tumor relapse to the bone appears to be increasing over the years, likely due to a longer overall survival of prostate cancer patients. Bone tropism represents an intriguing c...

  8. 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.

  9. 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.

  10. 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.

  11. 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 ...

  12. 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....

  13. High-Intensity Focused Ultrasound for the Treatment of Localized and Locally Advanced Hormone-Resistant Prostate Cancer: 2,5 Year Outcome

    Science.gov (United States)

    Solovov, V. A.; Dvoynikov, S. Y.; Vozdvizhenskiy, M. O.

    2011-09-01

    Introduction & Objectives: High-Intensity Focused Ultrasound (HIFU) has been shown to be a successful treatment for localised prostate cancer (PC). Here we have explored the effectiveness of the HIFU treatment for hormone-resistant prostate cancer (HRPC). Materials & Methods: 341 patients were treated in our center between September 2007 and December 2009; all of them showed treatment failure following hormone ablation. The median time before hormone-resistance was 20 (3-48) months. In the group with localised PC: number of patients 237, Gleason score ≤7, stage T1-2N0M0, age 69 (60-89) years, mean PSA before treatment 40,0 (5,8-92,9) ng/ml, mean prostate volume—39,3 (28-92) cc; in the group with locally advanced PC: number of patients 104, Gleason score ≤9, stage T2-3N0M0, age 72 (52-83) years, PSA before treatment 30,3 (20,1-60) ng/ml, mean prostate volume—41,2 (25-198) cc. HIFU was delivered under spinal anesthesia using the Ablatherm HIFU device (EDAP, France). Pre HIFU transurethral resection of the prostate (TURP) was performed for all patients. Mean follow-up time 18 months (3-30). Results: The median PSA level 12 months after HIFU treatment was 0,04 (0-2,24) ng/ml—localised PC, and for locally advanced disease—0,05 (0-48,4) ng/ml, at 18 months after HIFU treatment this was 0,2 (0,02-2,0) ng/ml for localised PC, and for locally advanced disease 0,18 (0,04-7,45) ng/ml. Patients with localised PC has 4,5% recurrence, those with locally advanced PC 20%. Kaplan-Meir analyses of the total group indicated that the risk of recurrence after 1 year follow-up was 10%, the risk of recurrence was 19% after 2 years of follow-up. Conclusions: Our initial experience shows that ultrasound ablation is safe, minimally invasive and effective as a treatment for localised and locally advanced hormone-resistant prostate cancer.

  14. Oligometastases in prostate cancer: restaging stage IV cancers and new radiotherapy options

    International Nuclear Information System (INIS)

    There are various subgroups of patients with metastatic prostate cancer: polymetastatic, oligometastatic, or oligo-recurrent cancers whose progression follows different courses and for whom there are different treatment options. Knowledge of tumor dissemination pathways and different genetic and epigenetic tumor profiles, as well as their evolution during disease progression, along with new diagnostic and therapeutic advances has allowed us to address these situations with local ablative treatments such as stereotactic body radiation therapy or stereotactic radiosurgery. These treatments provide high rates of local control with low toxicity in metastatic spread for primary cancers including those of pulmonary, digestive, and renal origin, while these types of treatments are still emerging for cancers of prostatic origin. There are several retrospective studies showing the effectiveness of such treatments in prostate cancer metastases, which has led to the emergence of prospective studies on the issue and even some phase II studies intended to prevent or delay systemic treatments such as chemotherapy. Here we collect together and review these past experiences and the studies currently underway. These types of radiotherapy treatments redefine how we approach extracranial metastatic disease and open up new possibilities for combination therapy with new systemic treatment agents

  15. Genetic epidemiology of prostate cancer

    OpenAIRE

    Wiklund, Fredrik

    2004-01-01

    Prostate cancer is a major health burden throughout the world, yet the etiology of prostate cancer is poorly understood. Evidence has accumulated supporting the existence of a hereditary form of this disease. Improved understanding of the genetic mechanisms underlying the development and progression of prostate cancer would be a major advance for improved prevention, detection and treatment strategies. This thesis evaluates different aspects of the genetic epidemiology of prostate cancer. In ...

  16. Prostate cancer: emerging pharmacotherapeutic modalities

    OpenAIRE

    Pratap Shankar; Anoop Kumar Verma; Rakesh Kumar Dixit; Amod Kumar Sachan

    2013-01-01

    Prostate cancer is the most common cancer in the world due to factors like old age, family history, ethnicity, diet and some elements exposure, with lot of controversies regarding prevention of prostate cancer. Though the exact pathogenesis is not clear, epidemiological evidence supports a relationship between prostate cancer and hormone levels. In this review article we are focusing on the advances in different pharmacotherapeutic modalities i.e. Chemoprevention, Prostate-Specific Antigen, H...

  17. 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.

  18. TRAPEZE: a randomised controlled trial of the clinical effectiveness and cost-effectiveness of chemotherapy with zoledronic acid, strontium-89, or both, in men with bony metastatic castration-refractory prostate cancer.

    Science.gov (United States)

    James, Nicholas; Pirrie, Sarah; Pope, Ann; Barton, Darren; Andronis, Lazaros; Goranitis, Ilias; Collins, Stuart; McLaren, Duncan; O'Sullivan, Joe; Parker, Chris; Porfiri, Emilio; Staffurth, John; Stanley, Andrew; Wylie, James; Beesley, Sharon; Birtle, Alison; Brown, Janet; Chakraborti, Prabir; Russell, Martin; Billingham, Lucinda

    2016-01-01

    BACKGROUND: Bony metastatic castration-refractory prostate cancer is associated with a poor prognosis and high morbidity. TRAPEZE was a two-by-two factorial randomised controlled trial of zoledronic acid (ZA) and strontium-89 (Sr-89), each combined with docetaxel. All have palliative benefits, are used to control bone symptoms and are used with docetaxel to prolong survival. ZA, approved on the basis of reducing skeletal-related events (SREs), is commonly combined with docetaxel in practice, although evidence of efficacy and cost-effectiveness is lacking. Sr-89, approved for controlling metastatic pain and reducing need for subsequent bone treatments, is generally palliatively used in patients unfit for chemotherapy. Phase II analysis confirmed the safety and feasibility of combining these agents. TRAPEZE aimed to determine the clinical effectiveness and cost-effectiveness of each agent. METHODS: Patients were randomised to receive six cycles of docetaxel plus prednisolone: alone, with ZA, with a single Sr-89 dose after cycle 6, or with both. Primary outcomes were clinical progression-free survival (CPFS: time to pain progression, SRE or death) and cost-effectiveness. Secondary outcomes were SRE-free interval (SREFI), total SREs, overall survival (OS) and quality of life (QoL). Log-rank test and Cox regression modelling were used to determine clinical effectiveness. Cost-effectiveness was assessed from the NHS perspective and expressed as cost per additional quality-adjusted life-year (QALY). An additional analysis was carried out for ZA to reflect the availability of generic ZA. RESULTS: PATIENTS: 757 randomised (median age 68.7 years; Eastern Cooperative Oncology Group scale score 0, 40%; 1, 52%; 2, 8%; prior radiotherapy, 45%); median prostate-specific antigen 143.78 ng/ml (interquartile range 50.8-353.9 ng/ml). Stratified log-rank analysis of CPFS was statistically non-significant for either agent (Sr-89, p = 0.11; ZA, p = 0.45). Cox regression

  19. Mitochondrial DNA determines androgen dependence in prostate cancer cell lines

    OpenAIRE

    Higuchi, M; Kudo, T; Suzuki, S.; Evans, TT; Sasaki, R.; Wada, Y; Shirakawa, T.; Sawyer, JR; Gotoh, A

    2006-01-01

    Prostate cancer progresses from an androgen-dependent to androgen-independent stage after androgen ablation therapy. Mitochondrial DNA plays a role in cell death and metastatic competence. Further, heteroplasmic large-deletion mitochondrial DNA is verycommon in prostate cancer. To investigate the role of mitochondrial DNA in androgen dependence of prostate cancers, we tested the changes of normal and deleted mitochondrial DNA in accordance with the progression of prostate cancer. We demonstra...

  20. Phase II Study of Biweekly Plitidepsin as Second-Line Therapy for Advanced or Metastatic Transitional Cell Carcinoma of the Urothelium

    Directory of Open Access Journals (Sweden)

    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.

  1. RHAMM (CD168) Is Overexpressed at the Protein Level and May Constitute an Immunogenic Antigen in Advanced Prostate Cancer Disease1

    OpenAIRE

    Kilian M. Gust; Hofer, Matthias D; Sven R. Perner; Kim, Robert; Arul M. Chinnaiyan; Varambally, Sooryanarayana; Moller, Peter; Rinnab, Ludwig; Rubin, Mark A; Greiner, Jochen; Schmitt, Michael; Kuefer, Rainer; Ringhoffer, Mark

    2009-01-01

    Localized prostate cancer (CaP) can be cured using several strategies. However, the need to identify active substances in advanced tumor stages is tremendous, as the outcome in such cases is still disappointing. One approach is to deliver human tumor antigen-targeted therapy, which is recognized by T cells or antibodies. We used data mining of the Cancer Immunome Database (CID), which comprises potential immunologic targets identified by serological screening of expression libraries. Candidat...

  2. Androgen deprivation therapy sensitizes prostate cancer cells to T-cell killing through androgen receptor dependent modulation of the apoptotic pathway

    OpenAIRE

    Ardiani, Andressa; Gameiro, Sofia R.; Kwilas, Anna R.; Donahue, Renee N.; Hodge, James W.

    2014-01-01

    Despite recent advances in diagnosis and management, prostrate cancer remains the second most common cause of death from cancer in American men, after lung cancer. Failure of chemotherapies and hormone-deprivation therapies is the major cause of death in patients with castration-resistant prostate cancer (CRPC). Currently, the androgen inhibitors enzalutamide and abiraterone are approved for treatment of metastatic CRPC. Here we show for the first time that both enzalutamide and abiraterone r...

  3. 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

  4. 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.

  5. 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.

  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. 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.

  8. Immunotherapy of distant metastatic disease

    DEFF Research Database (Denmark)

    Schadendorf, D; Algarra, S M; Bastholt, L;

    2009-01-01

    vaccines based on dendritic cells and peptides is driven by advances in understanding antigen presentation and processing, and by new techniques of vaccine preparation, stabilisation and delivery. Several agents that have shown promising activity in metastatic melanoma including IL-21 and monoclonal...

  9. 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.

  10. Tumor-Associated Antigens for Specific Immunotherapy of Prostate Cancer

    International Nuclear Information System (INIS)

    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+ cytotoxic T lymphocytes (CTLs) efficiently recognize and destroy tumor cells. CD4+ 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

  11. Periostin is up-regulated in high grade and high stage prostate cancer

    Directory of Open Access Journals (Sweden)

    Schraml Peter

    2010-06-01

    Full Text Available Abstract Background Expression of periostin is an indicator of epithelial-mesenchymal transition in cancer but a detailed analysis of periostin expression in prostate cancer has not been conducted so far. Methods Here, we evaluated periostin expression in prostate cancer cells and peritumoural stroma immunohistochemically in two independent prostate cancer cohorts, including a training cohort (n = 93 and a test cohort (n = 325. Metastatic prostate cancers (n = 20, hormone refractory prostate cancers (n = 19 and benign prostatic tissues (n = 38 were also analyzed. Results In total, strong epithelial periostin expression was detectable in 142 of 418 (34.0% of prostate carcinomas and in 11 of 38 benign prostate glands (28.9%. Increased periostin expression in carcinoma cells was significantly associated with high Gleason score (p Conclusions Our data indicate that periostin up-regulation is related to increased tumour aggressiveness in prostate cancer and might be a promising target for therapeutical interventions in primary and metastatic prostate cancer.

  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. 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.

  14. CHROMOGRANIN-A IN THE DIAGNOSIS OF PROSTATE CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Sivkov

    2015-01-01

    Full Text Available The principal marker of neuroendocrine differentiation (NED is chromogranin A (HGA. The purpose of this work is to determine the role of NED in diseases of the prostate gland by the level of HGA.Materials and methods. The study included 304 men with various diseases of the prostate: BPH - 20; chronic prostatitis (CP - 22; BPH and prostatic low-grade intraepithelial neoplasia (BPH+LDPIN - 50; BPH and high degree PIN (BPH+HGPIN - 32; localized prostate cancer (LPC - 80; locally advanced PCA (LAPC - 21; CRPC - 51. The last group United in patients LPC, LAPC and metastatic prostate cancer. All these groups of patients were performed blood sampling fasting with further definition of the level of HGA in serum by enzyme immunoassay. The reference values of HGA for this method are ranged from 0 to 3 nmol/L.Results. During the analyzing of the results of the study they revealed a general trend of increasing of mean values of HGA of serum with the growth stage of prostate cancer, with a maximum of patients with CRPC. According to the analysis they revealed no significant correlation between age and HGA (r = 0,05 among all study groups. They noted the persistent correlation (r = 0,32; p <0,001 between HGA and PSA levels among all studied groups of patients. They traced some relationship between the amount of points Gleason and HGA (r = 0,19; p <0,05 in cases of LPC, LAPC and CRPC. Defining the relationship between HGA and stage of prostate cancer (LPC, LAPC and CRPC, we also found a correlation (r = 0,31, p <0,005 among these groups of patients.Conclusions. HGA is a high interest for the early detection CRPC. Also with the help of HGA it seem to be quite promising to discover the most aggressive forms of prostate cancer. Definition of NED-tumor may be necessary for the analysis of a comprehensive approach to prostate cancer treatment selection.

  15. 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

  16. 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.

  17. Clinical Implications of Hedgehog Pathway Signaling in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Daniel L. Suzman

    2015-09-01

    Full Text Available Activity in the Hedgehog pathway, which regulates GLI-mediated transcription, is important in organogenesis and stem cell regulation in self-renewing organs, but is pathologically elevated in many human malignancies. Mutations leading to constitutive activation of the pathway have been implicated in medulloblastoma and basal cell carcinoma, and inhibition of the pathway has demonstrated clinical responses leading to the approval of the Smoothened inhibitor, vismodegib, for the treatment of advanced basal cell carcinoma. Aberrant Hedgehog pathway signaling has also been noted in prostate cancer with evidence suggesting that it may render prostate epithelial cells tumorigenic, drive the epithelial-to-mesenchymal transition, and contribute towards the development of castration-resistance through autocrine and paracrine signaling within the tumor microenvironment and cross-talk with the androgen pathway. In addition, there are emerging clinical data suggesting that inhibition of the Hedgehog pathway may be effective in the treatment of recurrent and metastatic prostate cancer. Here we will review these data and highlight areas of active clinical research as they relate to Hedgehog pathway inhibition in prostate cancer.

  18. 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.

  19. 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

  20. LDR 1921r Brachytherapy(BRA) for locally advanced prostatic adenocarcinoma. Pilot study

    International Nuclear Information System (INIS)

    From 1/91 to 4/95, 24 patients have been treated with combined BRA and External Beam Radiotherapy(EBRT). The mean age of the patients was 68 Y. A2, B1, B2, C and D1 stages were present respectively in 1,1, 14, 6 and 2 patients. The mean pretreatment PSA value was 22 ng/ml. BRA consisted in the placement of intraprostatic Plastic Catheters with the aid of the Martinez Applicator(MA), under laparotomy for 18 patients or under echographic control for the last 6. The MA was then retracted and the Tubes sutured to the perineum so the patients could walk in the treatment room thereafter. The next day, after a CT Scan control, the Tubes were loaded with 192Ir. The Paris System(PS) of dosimetry was used. The mean Basal Dose was 11.48Gy/day. In reality the mean Minimum Peripheral Dose(MPD) was 52Gy, while the 85% and 70% isodoses of the PS were surrounding the target volume in 50% of the patients each. The mean dose delivered to the anterior rectal wall was 46Gy. 5 days latter, EBRT was commenced for delivering 50Gy ICRU(25X2 Gy in 5 W) in the pelvis while shielding at 26Gy the volume of the 35Gy BRA isodose. The mean follow-up is 26 months. The mean time for PSA to decrease to values < 3ng/ml is 5.4 months and it normalized at 18 months in 91% of cases. (13(14)) biopsies realized systematically at 18 months were negative. Until now, 4 recurrences were diagnosed. The patient whose biopsy was positive at 18 months as well as one patient whose cancer nodule never disappeared were considered having local recurrence. The other 2 developed bone metastases. The second patient treated in our study developed a grade IV rectitis explained by the too small vicinity between a catheter and the rectal mucosa(5mm). The 8th patient implanted under laparotomy developed a postoperative bleeding inducing a grade III urinary complication. Afterwards, no major problem was met. This technic combining BRA and EBRT allows to deliver total cumulated MPD of 75Gy in the prostate while treating more