Prescribing practices for tumour aggressiveness and castration resistance in risk-stratified prostate cancer patients

2020 ◽  
Vol 2 (7) ◽  
pp. 392-397
Author(s):  
Meenakshi Meenu ◽  
Dharamvir Singh Arya
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Essential Medicines ◽  
World Health ◽  
Cancer Drug ◽  
Prescription Data ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Prescribing Practices ◽  
Castration Resistant

Capturing real-world prescription data is important for evaluating clinical practice in prostate cancer. The aim of this study was to evaluate prescribing practices in prostate cancer. This was a cross-sectional study in which four groups were identified based on tumour aggressiveness (bone metastasis absent and bone metastasis presnt) and castration response (castration-sensitive prostate cancer and castration-resistant prostate cancer). Drug utilisation methodology and core indicators of World Health Organization were used. A total of 150 patients were stratified into the four groups. The most common regime was complete androgen blockade in both bone metastasis groups and castration-sensitive prostate cancer. Palliative radiotherapy was part of the management in the bone metastasis (present) group. In castration-resistant prostate cancer, abiraterone, fosfestrol, docetaxel, and enzalutamide were prescribed. Approximately 78% of prescriptions contained medicines from the National List of Essential Medicines, India, 2015. Polypharmacy was not a common practice, antibiotics and antidepressant medicines were rarely prescribed. The prescribing trend for prostate cancer conformed to National Comprehensive Cancer Network guidelines.

scholarly journals Selective degradation of AR-V7 to overcome castration resistance of prostate cancer

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yuan Liu ◽  
Cuifu Yu ◽  
Zhenlong Shao ◽  
Xiaohong Xia ◽  
Tumei Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Selective Inhibition ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Selective Degradation ◽  
Castration Resistant ◽  
Novel Drugs ◽  
The Stability ◽  
Androgen Receptor Splice Variant

AbstractAndrogen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.

scholarly journals Incidence of Skeletal-Related Events in Patients with Castration-Resistant Prostate Cancer: An Observational Retrospective Cohort Study in the US

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Alison Tse Kawai ◽  
David Martinez ◽  
Catherine W. Saltus ◽  
Zdravko P. Vassilev ◽  
Montse Soriano-Gabarró ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Incidence Rate ◽  
Incidence Rates ◽  
Negative Consequences ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Castration Resistant ◽  
The Us ◽  
History Of ◽  
Skeletal Related Events

Background and Objective. Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased mortality. We estimated incidence rates of first SREs in a cohort of men with CRPC in the Surveillance, Epidemiology, and End Results-Medicare database. Methods. We included men aged ≥ 65 years with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy (other than nonmelanoma skin cancer) and had surgical or medical castration with subsequent second-line systemic therapy, which was used to infer castration resistance. The first occurrence of an SRE (fracture, bone surgery, radiation therapy, or spinal cord compression) in Medicare claims was identified. Incidence rates of SREs were estimated in all eligible person-time and, in secondary analyses, stratified by any use of bone-targeted agents (BTAs) and history of SRE. Results. Of 2,234 men with CRPC (84% white, mean age = 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the incidence rate of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The incidence rate of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any BTA use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. The incidence rate in patients with no history of SRE was 3.33 (95% CI 3.01-3.68) per 100 person-months, and in patients who had such a history, it was 4.20 (95% CI 3.84-4.58) per 100 person-months. Conclusions. In this large cohort of elderly men with CRPC in the US, SREs were common. A decrease in incidence of SREs after starting BTA is suggested, but the magnitude of the effect may be confounded by indication and other factors such as age and prior SRE.

scholarly journals Reinduction of Hormone Sensitivity to Goserelin following Chemotherapy with Vinorelbine in Castration-Resistant Prostate Cancer

2010 ◽  
Vol 10 ◽  
pp. 1814-1817
Author(s):  
Tal Grenader ◽  
Anthony Goldberg
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Serum Levels ◽  
Symptomatic Improvement ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Luteinizing Hormone Releasing Hormone ◽  
Androgen Ablation ◽  
Castration Resistant ◽  
Cessation Of Treatment

Primary androgen ablation leads to symptomatic improvement and a reduction in prostate-specific antigen (PSA) serum levels in patients with advanced prostate cancer, but all patients eventually become refractory to hormone therapy with progression of the disease and a life expectancy of about a year. We describe a patient who developed castration resistance, was treated with vinorelbine, and continues to be progression free on therapy with luteinizing hormone releasing hormone agonists alone, more than 2.5 years following cessation of treatment with vinorelbine.

scholarly journals Arginine vasopressin receptor 1a is a therapeutic target for castration-resistant prostate cancer

2019 ◽  
Vol 11 (498) ◽  
pp. eaaw4636 ◽  
Author(s):  
Ning Zhao ◽  
Stephanie O. Peacock ◽  
Chen Hao Lo ◽  
Laine M. Heidman ◽  
Meghan A. Rice ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Arginine Vasopressin ◽  
Ectopic Expression ◽  
Vasopressin Receptor ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Castration Resistant ◽  
Promising Therapeutic Approach

Castration-resistant prostate cancer (CRPC) recurs after androgen deprivation therapy (ADT) and is incurable. Reactivation of androgen receptor (AR) signaling in the low androgen environment of ADT drives CRPC. This AR activity occurs through a variety of mechanisms, including up-regulation of AR coactivators such as VAV3 and expression of constitutively active AR variants such as the clinically relevant AR-V7. AR-V7 lacks a ligand-binding domain and is linked to poor prognosis. We previously showed that VAV3 enhances AR-V7 activity to drive CRPC progression. Gene expression profiling after depletion of either VAV3 or AR-V7 in CRPC cells revealed arginine vasopressin receptor 1a (AVPR1A) as the most commonly down-regulated gene, indicating that this G protein–coupled receptor may be critical for CRPC. Analysis of publicly available human PC datasets showed thatAVPR1Ahas a higher copy number and increased amounts of mRNA in advanced PC. Depletion of AVPR1A in CRPC cells resulted in decreased cell proliferation and reduced cyclin A. In contrast, androgen-dependent PC, AR-negative PC, or nontumorigenic prostate epithelial cells, which have undetectableAVPR1AmRNA, were minimally affected by AVPR1A depletion. Ectopic expression of AVPR1A in androgen-dependent PC cells conferred castration resistance in vitro and in vivo. Furthermore, treatment of CRPC cells with the AVPR1A ligand, arginine vasopressin (AVP), activated ERK and CREB, known promoters of PC progression. A clinically safe and selective AVPR1A antagonist, relcovaptan, prevented CRPC emergence and decreased CRPC orthotopic and bone metastatic growth in mouse models. Based on these preclinical findings, repurposing AVPR1A antagonists is a promising therapeutic approach for CRPC.

CASTRATION-RESISTANT PROSTATE CANCER: NEW PERSPECTIVES IN PHARMACOLOGICAL TREATMENT

2019 ◽  
Vol 25 (1) ◽  
pp. 49-58
Author(s):  
Dmitry A. Andreev ◽  
A. A Zavyalov ◽  
A. V Govorov ◽  
K. A. Kokushkin ◽  
M. Y Davidovskaya
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Treatment Options ◽  
Specific Treatment ◽  
Cochrane Library ◽  
Cancer Drug ◽  
Castration Resistant Prostate Cancer ◽  
Optimal Sequence ◽  
Treatment Algorithms ◽  
Castration Resistant

Prostate cancer remains one of the most actual problems in oncourology due to its high prevalence and resistance to therapy. Within 5 years of active treatment and follow-up, the castration-resistant prostate cancer (CRPC) develops in 10-20% of patients. This type of disease course resists treatments and leads to death. Medical resources distinguish two different forms of CRPC: non-metastatic and metastatic. Such separation is critically important because each of two forms requires different treatment algorithms. This paper summarizes the main outlines of foreign clinical guidelines and reviews the new treatment options for non-metastatic and metastatic CRPC as wells as the design and results of key clinical trials on drug efficiency. To prepare the review, the comprehensive literature search was conducted using PubMed/Medline, the Cochrane Library, EMBASE, CyberLeninka, e-library databases. The search line included phrases containing the following words: prostate cancer, castration-resistant prostate cancer, drug therapy, treatment algorithms, clinical studies, etc. In accordance to foreign guidelines, it is essential to determine the high risk patients with non-metastatic CRPC and promptly apply new therapeutic options including apalutamide and enzalutamide, which have proven being effective in clinical trials as therapies that attenuate the transition of the non-metastatic CRPC to the metastatic stage. Foreign medical guidelines propose to apply a wider set of treatment algorithms for patients with metastatic CRPC, for instance: considerations on possibilities to use the cabazitaxel instead of docetaxel in the 1st line therapy in patients with pre-existing mild peripheral neuropathy, etc. as well as new therapies - pembrolizumab and sipuleucel-T. The issues regarding the selection of patients with CRPC for specific treatment algorithms and defining the optimal sequence of therapeutic regimens as well as combining various regimens with minimizing toxic effects and maximizing patient benefits remain unsolved.

Evaluation of bone metastasis of castration-resistant prostate cancer after enzalutamide and abiraterone using Bone Scan Index on bone scintigraphy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e596-e596
Author(s):  
Suguru Kadomoto ◽  
Kouji Izumi ◽  
Takahiro Nohara ◽  
Konaka Hiroyuki ◽  
Yoshifumi Kadono ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Metastasis ◽  
Bone Metastases ◽  
Bone Scintigraphy ◽  
Bone Scan ◽  
Average Rate ◽  
Castration Resistant Prostate Cancer ◽  
Bone Scan Index ◽  
Castration Resistant ◽  
Better Than

e596 Background: It was ambiguous till now to evaluate the change of bone metastasis by various treatments. To quantify the change of bone metastases by enzalutamide, abiraterone, and docetaxel for the castration-resistant prostate cancer (CRPC) with bone metastases (bmCRPC), we employed Bone Scan Index (BSI) on bone scintigraphy. Methods: We retrospectively evaluated the change of PSA and bone metastases of CRPC patients who were treated with enzalutamide (Enz), abiraterone (Abi) and/or docetaxel (DOC) in our hospital. All patients underwent Tc-99m MDP bone scintigraphy. The degree of bone metastases was analyzed using BSI, which was calculated by BONENAVI (FUJIFILM RI Pharma, Japan; EXINIbone, EXINI Diagnostics, Sweden). 19 patients were treated with enzalutamide (8 cases: pre-docetaxel, 11 cases: post-docetaxel). The median PSA of patients treated with Enz was 12.64 ng/ml (1.63-199 ng/ml). And 11 patients were treated with abiraterone (5 cases: pre-docetaxel, 6 cases: post-docetaxel). The median PSA of patients treated with Abi was 26.37 ng/ml (2.29-199 ng/ml). Results: We observed decline of PSA in 18/30 cases (9 cases: pre-DOC, 9 cases: post-DOC). Decline of PSA to 50% or more was observed in 14 cases. In contrast, decline of BSI was observed in 53.3% (16/30) cases and decline of PSA to 25% or more was observed in only 6 cases. BSI decreased in 84.6% (11/13) of pre-DOC setting and in 29.4% (5/17) of post-DOC setting indicating that change of BSI was poor in post-DOC setting. However, DOC had already decreased BSI in 91.7% (11/12) before Abi or Enz treatment. Moreover, the average rate of BSI decline in the patients that BSI decreased by DOC was better than the patients that BSI decreased by Abi/Enz (-48.46% vs -28.56%). Finally, although the rate of BSI change by Enz was weakly correlated with the rate of PSA decline (y = 0.3906x + 25.35, R2 = 0.3423), BSI continued to increase in four cases in spite of PSA decline. Conclusions: BSI using BONENAVI on bone scintigraphy was helpful for evaluating the effectiveness of treatment and following-up of bmCRPC.

Retrospective analysis of fatigue in men with metastatic castration-resistant prostate cancer treated with enzalutamide.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 374-374 ◽  
Author(s):  
Srikala S. Sridhar ◽  
Alan D. Smith ◽  
Nazanin Fallah-Rad ◽  
Aaron Richard Hansen
Keyword(s):  
Prostate Cancer ◽  
Common Side Effect ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Castration Resistant ◽  
Disease Characteristics ◽  
Psa Response ◽  
Comorbidity Index ◽  
Concomitant Medications ◽  
Relevant Factors

374 Background: Enzalutamide (E) improves survival in men with metastatic castration-resistant prostate cancer (mCRPC). Fatigue (F) while taking E is poorly understood and may limit the use of this life-prolonging drug. Methods: All men treated with E for mCRPC at Princess Margaret Cancer Centre from August 2010 and July 2016 were included. Relevant factors collected, include age, ECOG, Charleston Comorbidity Index, disease characteristics, prior therapies, concomitant medications, and details regarding E treatment and response. Univariate (UVA) and multivariate (MVA) analysis were performed using logistic regression. Results: 415 men started E for mCRPC during this period. Median age at diagnosis was 66 years (range 42-94) and median time to castration-resistance (TTCR) was 113 days. Prior therapies included docetaxel (21%) and abiraterone (26%). Bone was the most common site of metastasis (76%) followed by lymph nodes (45%) and visceral (20%). Concurrent corticosteroid use was 18% and PSA response (≥50%) rate was 55%. Median duration on E was 224 days. F on E occurred in 178 patients (43%) and 56 (13%) men required a dose-reduction due to F. 26 men (6%) stopped E due to F (Table). Conclusions: F is an important and common side effect of E in men with mCRPC. Duration of exposure to androgen deprivation, markers of systemic inflammation (such as increased NLR and platelets) and advanced age appear to be associated with E-related F and difficulty administering drug. There was no association between corticosteroid use and E-related F and difficulty administering drug. [Table: see text]

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