scholarly journals The Changing Therapeutic Landscape in Metastatic Prostate Cancer

2017 ◽  
Vol 13 (02) ◽  
pp. 112
Author(s):  
Alan J Koletsky ◽  
Keyword(s):  
Prostate Cancer ◽  
Metastatic Disease ◽  
Metastatic Prostate Cancer ◽  
Focal Point ◽  
Castration Resistant Prostate Cancer ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Truncating Mutation ◽  
Radium 223 ◽  
Phosphoinositide 3 Kinase

Over the past several years a number of novel and diverse agents have provided a significant clinical benefit for patients with metastatic castration-resistant prostate cancer including abiraterone, enzalutamide, sipuleucel-T, cabazitaxel, and radium-223. The early use of docetaxel or abiraterone at initiation of standard androgen deprivation therapy in patients with metastatic hormone-sensitive prostate cancer has also led to substantial improvements in overall survival. The identification of a truncating mutation in the androgen receptor (ARV7), a biomarker of resistance, may help clarify a more optimal sequencing of hormonal and chemotherapy-based therapies for patients with metastatic disease. The genomic landscape of both primary and metastatic prostate cancer has been an important focal point of translational research. The most widely studied pathways that affect tumorigenesis are the phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/protein kinase B (AKT) and poly ADP ribose polymerase (PARP) and DNA repair pathways. This review will highlight recent clinical trials which have had a major impact on the management of patients with metastatic disease with an emphasis on treatments driven by common genomic aberrations present in advanced prostate cancer.

scholarly journals Metasztatikus hormonérzékeny prosztatadaganat korszerű kezelése

2018 ◽  
Vol 159 (41) ◽  
pp. 1664-1671
Author(s):  
Zsófia Küronya ◽  
Krisztina Bíró ◽  
Lajos Géczi ◽  
Anikó Maráz
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223 ◽  
Sensitive Phase ◽  
Hormone Sensitive ◽  
To Receive

Abstract: The treatment of metastatic prostate cancer can be divided into two pathophysiological phases: hormone-sensitive and castration-resistant phases. Huggins’ observation in the year 1941, which was awarded with the Nobel Prize in 1966, has a key role in treatment during the hormone-sensitive phase, stating that if the testicles are removed, the size of the prostate cancer decreases. Inducing androgen deprivation, i.e., testosterone depletion is the basic treatment of metastatic prostate cancer that patients have to receive life-long. In the past eight years, five new agents have been approved besides docetaxel in the treatment of metastatic castration-resistant prostate cancer: sipuleucel-T, cabazitaxel, abiraterone, enzalutamide, and radium-223. With the sequential application of these agents, significant improvement can be achieved in survival. Besides the latest developments, the hormone-sensitive phase has become the focus of attention, especially in the treatment of patients with de novo metastases and poor prognosis. Many studies have proven the outstanding efficacy of adding early docetaxel and abiraterone to androgen deprivation therapy. The authors give a detailed overview of clinical studies leading to a paradigm change in treatment during the hormone-sensitive phase, and call attention to the difficulties encountered in Hungarian practice. Orv Hetil. 2018; 159(41): 1664–1671.

scholarly journals Early alkaline phosphatase dynamics as biomarker of survival in metastatic castration-resistant prostate cancer patients treated with radium-223

2021 ◽  
Author(s):  
Maarten J. van der Doelen ◽  
Agnes Stockhaus ◽  
Yuanjun Ma ◽  
Niven Mehra ◽  
Jeffrey Yachnin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alkaline Phosphatase ◽  
Confidence Interval ◽  
Surrogate Marker ◽  
Response Monitoring ◽  
Castration Resistant Prostate Cancer ◽  
Related Event ◽  
Castration Resistant ◽  
Radium 223 ◽  
Skeletal Related Event

Abstract Purpose Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS). Methods This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate. Results A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5–15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73–3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients. Conclusion Early treatment–induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.

scholarly journals Esthetic and Functional Improvement of Asymmetric Lower Limb Overgrowth in a Proteus Syndrome Patient: a Combined Surgical Technique

2021 ◽  
Author(s):  
Francesca Riccardi ◽  
Simone Catapano ◽  
Giuseppe Cottone ◽  
Dino Zilio ◽  
Luca Vaienti
Keyword(s):  
Adipose Tissue ◽  
Lower Limb ◽  
Vascular Malformations ◽  
Functional Improvement ◽  
Proteus Syndrome ◽  
Phosphatase And Tensin Homolog ◽  
Tensin Homolog ◽  
Genetic Mosaicism ◽  
Phosphoinositide 3 Kinase ◽  
The Right

AbstractProteus syndrome is a rare, sporadic, congenital syndrome that causes asymmetric and disproportionate overgrowth of limbs, connective tissue nevi, epidermal nevi, alteration of adipose tissue, and vascular malformations. Genetic mosaicism, such as activating mutations involving protein kinase AKT1, phosphoinositide 3 kinase (PI3-K), and phosphatase and tensin homolog (PTEN), may be important causes of Proteus syndrome. However, many patients have no evidence of mutations in these genes. Currently, the diagnosis is clinical and based on phenotypic features. This article reports a case of Proteus syndrome in a 14-year-old female patient who presented with linear epidermal nevi, viscera anomalies, and adipose tissue dysregulation. She showed an asymmetric progressive overgrowth of the right lower limb after birth bringing relevant functional and esthetic consequences. Therefore, she asked a plastic surgery consultation and a surgical treatment with a combined technique was planned. With our approach, we were able to reduce leg diameter and improve joint mobility reliably and safely with satisfying esthetic results.

Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 5002-5002
Author(s):  
Silke Gillessen ◽  
Ananya Choudhury ◽  
Alejo Rodriguez-Vida ◽  
Franco Nole ◽  
Enrique Gallardo Diaz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Safety Analysis ◽  
Phase Iii ◽  
Fracture Rate ◽  
Castration Resistant Prostate Cancer ◽  
Continuous Administration ◽  
Castration Resistant ◽  
Radium 223 ◽  
Safety Population

5002 Background: The randomized phase III EORTC-1333-GUCG (NCT02194842) trial compares enzalutamide vs. a combination of Radium 223 and enzalutamide in asymptomatic or mildly symptomatic metastatic castration resistant prostate cancer (mCRPC) patients. The premature unblinding of ERA223 (NCT02043678) in Nov 2017 due to a significant increase in the rate of fractures in the combination of abiraterone and Ra223 arm led to the implementation of the mandatory use of bone protecting agents (BPA) in the EORTC-1333-GUCG trial. Skeletal fractures, pathological or not, are a frequent and underestimated adverse event of systemic treatment of advanced prostate cancer. Whether this mandated use of BPA (zoledronic acid or denosumab) would mitigate the risk of fractures in this patient population was unclear. An early safety analysis (Tombal, ASCO, 2019) suggested that the risk of fractures was well controlled in both arms when patients receive BPA. We present here an updated analysis of fracture incidence with longer follow-up. Methods: As of 28/01/2021, a total of 253 patients (134 after making BPA mandatory) were randomized between enzalutamide/Ra223 and enzalutamide. The fracture rate was estimated with the cumulative incidence method in the safety population of 237 (122 after making BPA mandatory) treated patients. Death in absence of fracture was analyzed as competing risk and censoring was applied at last follow-up. Results: Overall, 69.5% of enzalutamide/Ra223 patients (95.2% after making BPA mandatory) and 73.1% of enzalutamide patients (95% after making BPA mandatory) received BPA on treatment: 13.6% in the enzalutamide/Ra223 arm and 21.8% in the enzalutamide arm did not use BPA at registration, but started during protocol treatment and 55.9% and 51.3% respectively, received BPA since entry. At 36.7 months median follow-up in patients without BPA and 23.1 months median follow-up in patients receiving BPA, a total of 39 patients reported a fracture. Among them, 30 patients (20 in enzalutamide/Ra223 arm) did not receive BPA and 9 (4 in the enzalutamide/Ra223 arm) received BPA (see table). Conclusions: The updated safety analysis confirms the early fracture rate results. In the absence of BPA, the risk of fracture is increased when RA223 is added to enzalutamide. Strikingly, in both arms, the risk remains almost abolished by a preventive continuous administration of BPA, thus stressing the importance of complying to international recommendations in terms of giving BPA to mCRPC patients. This study is sponsored by EORTC and supported by Bayer and Astellas. Clinical trial information: NCT02194842. [Table: see text]

Sex Hormones and Prostate Cancer

2020 ◽  
Vol 71 (1) ◽  
pp. 33-45 ◽  
Author(s):  
Richard J. Auchus ◽  
Nima Sharifi
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Current Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
History Of ◽  
Prostate Cancer Research ◽  
Prostate Cancers ◽  
Androgen Independent ◽  
Transition Studies

The prostate is an androgen-dependent organ that develops only in male mammals. Prostate cancer is the most common nonskin malignancy in men and the second leading cause of cancer deaths. Metastatic prostate cancer initially retains its androgen dependence, and androgen-deprivation therapy often leads to disease control; however, the cancer inevitably progresses despite treatment as castration-resistant prostate cancer, the lethal form of the disease. Although it was assumed that the cancer became androgen independent during this transition, studies over the last two decades have shown that these tumors evade treatment via mechanisms that augment acquisition of androgens from circulating precursors, increase sensitivity to androgens and androgen precursors, bypass the androgen receptor, or a combination of these mechanisms. This review summarizes the history of prostate cancer research leading to the contemporary view of androgen dependence for prostate cancers and the current treatment approaches based on this modern paradigm.

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