Safety and efficacy of abiraterone acetate (AA) in patients aged 75 or more with metastatic castration-resistant prostate cancer (mCRPC) in both pre-chemotherapy or post-chemotherapy settings: Real-life experience from thirteen Italian centers.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 209-209
Author(s):  
Zuzana Sirotova ◽  
Giulia Courthod ◽  
Alfredo Tartarone ◽  
Orazio Caffo ◽  
Francesca Maines ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Elderly Patients ◽  
Liver Toxicity ◽  
Real Life ◽  
Castration Resistant Prostate Cancer ◽  
Synthesis Inhibitor ◽  
Good Tolerability ◽  
Efficient Treatment ◽  
Androgen Synthesis ◽  
Docetaxel Group

209 Background: Prostate cancer affects mainly elderly patients (pts) that have different comorbidities. AA is a selective androgen synthesis inhibitor that showed the efficacy in either chemotherapy (CT) naive pts or those pretreated with docetaxel. Its oral administration and good tolerability make it a manegeable treatment for elderly mCRPC pts. Methods: We collected retrospectively data regarding mCRPC pts aged ≥75 years treated with AA in 13 Italian Centers since April 2013. The median age was 79 years (r. 75-90) with 48% of pts being octagerians. Post CT pts had more extensive disease, higher baseline PSA and ECOG PS. Nearly all the pts had comorbidities, the most frequent being hypertension present in 146 pts (58%), 43 pts (17%) had diabetes type II. We evaluated duration of the AA treatment, overall response rate (ORR), 50% PSA decline, time to progression (TTP) and overall survival (OS). We reported all toxicities observed. Results: A total of 252 pts ,147 pre treated with docetaxel and 105 chemo naive, were included. Median duration of treatment with AA was 8,6 months in post CT and 11,5 in CT naive pts. ORR was 35,3% in pre docetaxel and 27,4% in post docetaxel group. 64 pts (65%) and 51 pts (46%) obtained 50% PSA reduction in pre and post docetaxel group, respectively. Median TTP was 8,6 in post docetaxel and 11,9 in CT naive pts. We observed a median OS of 13,8 months in post CT group while for CT naive pts data were not yet mature. AA was well tolerated with only 8 pts (3,2%) who discontinued treatment due to toxicity, while in 4 pts (1,6%) temporary dose reductions were performed. The most frequent G3 toxicities were hypertension and liver toxicity with 4 pts (1,6%) and 5 pts (2%), respectively. After progressing on AA, 85 pts (34%) received at least one subsequent treatment. 40 pts (15,9%) are still on treatment with AA. Conclusions: Even if almost all the pts reported comorbidities at AA start and 72 pts (28,6%) had PS ECOG 2, only a small proportion of them discontinued the treatment due to toxicity confirming that AA is well tolerated and efficient treatment also for elderly patients.

scholarly journals Minireview: Androgen Metabolism in Castration-Resistant Prostate Cancer

2013 ◽  
Vol 27 (5) ◽  
pp. 708-714 ◽  
Author(s):  
Nima Sharifi
Keyword(s):  
Prostate Cancer ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Synthesis Inhibitor ◽  
Androgen Independence ◽  
Androgen Synthesis ◽  
Androgen Receptor Antagonist ◽  
Castration Resistant ◽  
Hormonal Therapies ◽  
Additional Clinical Benefit

Abstract The decades-old terminology of androgen independence has been replaced in recent years with castration-resistant prostate cancer. Biological and clinical evidence have together conspired to support the use of this revised terminology by demonstrating that in the vast majority of cases tumors are neither truly depleted of androgens, nor are they free of the requirement for androgens to sustain growth and progression. Abiraterone acetate, an androgen synthesis inhibitor, and enzalutamide, a potent androgen receptor antagonist, both exploit the continued requirement for androgens. A central question, given the therapeutic gains enabled by further suppression of the androgen axis with these newer agents, is whether there may be additional clinical benefit gained by moving the goal posts of androgen suppression even further. The answer lies in part with the mechanisms utilized by tumors that enable resistance to these therapies. The aims of this review were to give a broad outline of steroidogenesis in prostate cancer and to highlight recent developments in understanding resistance to hormonal therapies.

scholarly journals Consequences of Different Corticosteroids on Serum Potassium and Prostate-Specific Antigen in Patients Receiving Abiraterone for Castration-Resistant Prostate Cancer: A Retrospective Observational Study

2017 ◽  
Vol 11 ◽  
pp. 117955491773773 ◽  
Author(s):  
Masaomi Tatsuzawa ◽  
Ryuichi Ogawa ◽  
Naoki Kinjo ◽  
Soan Kim ◽  
Fumitaka Shimizu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Antigen ◽  
Serum Potassium ◽  
Medical Records ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Synthesis Inhibitor ◽  
Androgen Synthesis ◽  
Castration Resistant

Background: Abiraterone acetate is an androgen synthesis inhibitor approved for the treatment of castration-resistant prostate cancer (CRPC). Although co-administration of either prednisone or prednisolone at 10 mg/d has been recommended to reduce the risk of abiraterone-induced hyperaldosteronism (notably hypokalemia) and to give adjunctive pain relief effects, whether these glucocorticoids can be substituted by dexamethasone remains unknown. Methods: We performed a retrospective review of medical records of patients who were given abiraterone for the treatment of CRPC with either prednisolone (ABI/PSL) 10 mg/d or dexamethasone (ABI/DEX) 0.5 or 1 mg/d between 2014 and 2017 in Juntendo University Nerima Hospital. Demographic and biochemical data including prostate-specific antigen (PSA) level were retrieved from the electronic medical records. Results: Fifty-three eligible patients (27 in ABI/PSL group and 26 in ABI/DEX group) were extracted from the records. Both groups showed no significant changes in serum potassium level before and after starting treatment. In the ABI/PSL group, 12 patients (46%) showed elevations of PSA and 7 patients (27%) discontinued treatment within 3 months. In contrast, in the ABI/DEX group, only 6 patients (25%) showed elevations of PSA and 3 patients (13%, all were given dexamethasone 1 mg/d) discontinued treatment. Conclusions: Dexamethasone and prednisolone may be equally effective in preventing abiraterone-induced hypokalemia.

scholarly journals Hematologic toxicity of radium-223 in elderly patients with metastatic Castration Resistant Prostate Cancer: a real-life experience

2019 ◽  
Vol 7 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Renato P. Costa ◽  
Sebastiano Bordonaro ◽  
Francesco Cappuccio ◽  
Vincenzo Tripoli ◽  
Alessandra Murabito ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Elderly Patients ◽  
Life Experience ◽  
Real Life ◽  
Hematologic Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Radium 223

Suppression of testosterone production using abiraterone acetate (AA) with or without androgen deprivation therapy (ADT) in metastatic castration resistant prostate cancer (mCRPC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5049-5049
Author(s):  
Gautam Gopalji Jha ◽  
Engle Jeff
Keyword(s):  
Prostate Cancer ◽  
Total Duration ◽  
Cost Savings ◽  
Androgen Deprivation ◽  
Castration Resistant Prostate Cancer ◽  
Synthesis Inhibitor ◽  
Cost Avoidance ◽  
Testosterone Levels ◽  
Androgen Synthesis ◽  
The Cost

5049 Background: Patients with metastatic prostate cancer (mPC) are treated with lifelong ADT even after progression and every treatment for mPC has been tested only in the setting of androgen deprivation. Androgen synthesis inhibitor AA which inhibits synthesis of androgen that later get converted to testosterone has been studied and approved only alongside ADT similar to all other agents that have no or limited activity on testosterone suppression. We reviewed the ability of AA to sufficiently suppress testosterone levels as compared to AA plus ADT and its potential impact on cost savings. Methods: This retrospective study included consecutive patients with mCRPC treated with AA alone or in combination with ADT (in absence of orchiectomy) who had been followed with serial testosterone values on therapy. A cost analysis was performed to determine the cost avoidance by omitting leuprolide injections while on AA. The cost avoidance was calculated by multiplying the total number of injections by the wholesale acquisition cost of $5252.86 for a three month leuprolide injection. Results: Of 57 patients included in the final analysis, 36 received AA plus ADT, 10 received AA alone, and 11 started off with AA plus ADT before transitioning to AA alone. Testosterone levels were drawn 235 times. Testosterone was undetectable (below < 2 ng/dl) in both arms, 134 of 152 in combination arm and 86 of 99 in the AA alone arm. The median testosterone concentration when detectable was 3 ng/dL in AA alone and 3.5 ng/dL in AA plus ADT. None in the combination arm and only one testosterone value in AA arm had testosterone > than 30 ng/dl. The mean duration of AA use in this study was close to one year, and the total duration of therapy was approximately 61 years which could result in elimination of 244 leuprolide administrations and approximately $1.29 million in total cost savings. Conclusions: AA alone is able to effectively suppress testosterone synthesis in patients with prostate cancer. ADT with GnRH agonist or antagonist can be safely withheld while on therapy with AA and testosterone values followed to confirm adequate androgen suppression. This has acquired new significance after studies in patients with hormone sensitive disease where median duration of treatment was 33 months which could translate to an avoidable expense of $55.5 million for 960 patients in ‘STAMPEDE’ study and $34.5 million in ‘LATITUDE’ study from leuprolide administration in combination arm.

scholarly journals KAT2A-mediated AR translocation into nucleus promotes abiraterone-resistance in castration-resistant prostate cancer

2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Dingheng Lu ◽  
Yarong Song ◽  
Ying Yu ◽  
Decai Wang ◽  
Bing Liu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcriptional Activity ◽  
Critical Role ◽  
Specific Antigen ◽  
Hormonal Treatment ◽  
Castration Resistant Prostate Cancer ◽  
Post Translational Modification ◽  
Synthesis Inhibitor ◽  
Androgen Synthesis ◽  
Castration Resistant

AbstractAbiraterone, a novel androgen synthesis inhibitor, has been approved for castration-resistant prostate cancer (CRPC) treatment. However, most patients eventually acquire resistance to this agent, and the underlying mechanisms related to this resistance remain largely unelucidated. Lysine acetyltransferase 2 A (KAT2A) has been reported to enhance transcriptional activity for certain histone or non-histone proteins through the acetylation and post-translational modification of the androgen receptor (AR). Therefore, we hypothesised that KAT2A might play a critical role in the resistance of prostate tumours to hormonal treatment. In this study, we found that KAT2A expression was increased in abiraterone-resistant prostate cancer C4-2 cells (C4-2-AbiR). Consistently, elevated expression of KAT2A was observed in patients with prostate cancer exhibiting high-grade disease or biochemical recurrence following radical prostatectomy, as well as in those with poor clinical survival outcomes. Moreover, KAT2A knockdown partially re-sensitised C4-2-AbiR cells to abiraterone, whereas KAT2A overexpression promoted abiraterone resistance in parental C4-2 cells. Consistent with this finding, KAT2A knockdown rescued abiraterone sensitivity and inhibited the proliferation of C4-2-AbiR cells in a mouse model. Mechanistically, KAT2A directly acetylated the hinge region of the AR, and induced AR translocation from the cytoplasm to the nucleus, resulting in increased transcriptional activity of the AR-targeted gene prostate specific antigen (PSA) leading to resistance to the inhibitory effect of abiraterone on proliferation. Taken together, our findings demonstrate a substantial role for KAT2A in the regulation of post-translational modifications in AR affecting CRPC development, suggesting that targeting KAT2A might be a potential strategy for CRPC treatment.

scholarly journals Abiraterone in chemotherapy-naive patients with metastatic castration-resistant prostate cancer: a systematic review of ‘real-life’ studies

2018 ◽  
Vol 10 (10) ◽  
pp. 305-315 ◽  
Author(s):  
Michele Marchioni ◽  
Petros Sountoulides ◽  
Maida Bada ◽  
Sebastiano Rapisarda ◽  
Cosimo De Nunzio ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Meta Analysis ◽  
Real Life ◽  
Castration Resistant Prostate Cancer ◽  
The Real ◽  
Castration Resistant ◽  
Real Life Setting ◽  
Grade 3 ◽  
Baseline Psa

Background: To assess the efficacy and safety of treatment with abiraterone acetate (AA) in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (mCRPC) in the ‘real-life’ setting. Methods: Data acquisition on the outcomes of the use of AA in chemotherapy-naive patients with mCRPC was performed by a MEDLINE comprehensive systematic literature search using combinations of the following key words: ‘prostate cancer’, ‘metastatic’, ‘castration resistant’, ‘abiraterone’, ‘real life’, and excluding controlled clinical trials (phase II and III studies). Identification and selection of the studies was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria. Outcomes of interest were overall survival (OS), progression-free survival (PFS), 12-week 50% reduction in prostate-specific antigen (PSA), and grade 3 and higher adverse events. Data were narratively synthesized in light of methodological and clinical heterogeneity. Results: Within the eight identified studies that fulfilled the criteria, a total of 801 patients were included in the meta-analysis. Baseline PSA ranged between 9.5 and 212.0 ng/ml. Most of the patients had bone metastases. Duration of treatment with AA was longer in the studies with lower baseline PSA levels. The median OS ranged between 14 and 36.4 months. The PFS, assessed according to different definitions, ranged from 3.9 to 18.5 months. A 50% PSA reduction at 12 weeks was reached by a variable percentage of patients ranging from 36.0% to 62.1%. Finally, the rate of grade 3 and higher adverse events was reported in three studies and ranged from 4.4% to 15.5%. Conclusions: Despite the high grade of heterogeneity among studies, treatment with AA seems to ensure good survival outcomes in the ‘real-life’ setting. However, prospective studies based on patients’ characteristics being more similar to ‘real-life’ patients are necessary.

2566 Cabazitaxel for metastatic castration-resistant prostate cancer (mCRPC) real data in real life

2015 ◽  
Vol 51 ◽  
pp. S499-S500
Author(s):  
R. Manneh Kopp ◽  
T. Alonso Gordoa ◽  
P. Celiz ◽  
J.M. Sepúlveda ◽  
E. Grande ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Real Life ◽  
Real Data ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Treatment characteristics for nonmetastatic castration-resistant prostate cancer in the United States, Europe and Japan

2019 ◽  
Vol 15 (35) ◽  
pp. 4069-4081 ◽  
Author(s):  
Ruchitbhai Shah ◽  
Marc Botteman ◽  
Reginald Waldeck
Keyword(s):  
Prostate Cancer ◽  
Eastern Cooperative Oncology Group ◽  
Patient Characteristics ◽  
The United States ◽  
Treatment Patterns ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Synthesis ◽  
Castration Resistant ◽  
The Us ◽  
Androgen Synthesis Inhibitors

Aim: We conducted this study to describe nonmetastatic castration-resistant prostate cancer (nmCRPC) patient characteristics and treatment patterns in the US, Europe and Japan. Materials & methods: Descriptive analyses were conducted using the 2015–2017 Ipsos Global Oncology Monitor Database. Results: A total of 2065 (442 in the US, 509 in Europe and 1114 in Japan) patients (median age: 74–80 years; stage III at diagnosis : 38.5%; Eastern Cooperative Oncology Group [ECOG] score ≤1: 79.4%; treated by urologist : 88.4%) were included in the analytic cohort. Luteinizing hormone-releasing hormone agonists and antiandrogens were the most commonly used first regimen treatments. With subsequent nmCRPC regimens their use decreased, while the use of chemotherapy, corticosteroids, androgen synthesis inhibitors and second-generation androgen receptor inhibitors increased. Conclusion: These data represent real-world treatment patterns in nmCRPC.

Sign in / Sign up

Export Citation Format

Share Document