Seizures and Neuropsychiatric Toxicity in Patients with Non-Metastatic CRPC Treated with New Antiandrogens: Systematic Review and Meta-Analysis

2021 ◽  
Vol 44 (4) ◽  
pp. 153-160
Author(s):  
Raquel Sopeña Sutil ◽  
Jorge Silva Ruiz ◽  
Borja Garcia Gomez ◽  
Javier Romero-Otero ◽  
Lucia Garcia-Gonzalez ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Control Group ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
History Of ◽  
Neuropsychiatric Toxicity ◽  
Grade 3 ◽  
Risk Ratios

Introduction: Recently, enzalutamide, apalutamide, and darolutamide have shown benefits in metastasis-free survival in non-metastatic castration-resistant prostate cancer (nmCRPC) patients compared to placebo. Previous evidence about the safety profile of these new androgens is limited. This meta-analysis studies seizure and neuropsychiatric effects of new anti-androgens compared to placebo in nmCRPC patients. Methods: PubMed and Cochrane databases were systematically reviewed until 1 March 2020 by 2 independent researchers using a pre-specified search strategy. Placebo-compared randomized controlled trials (RCTs) of nmCRPC patients treated with new anti-androgens providing data on neuropsychiatric events and seizures were included. Variables were seizure, headache, mental impairment, and dizziness. Pooled risk ratios (RR) were calculated using the Mantel-Hansel random effects model and Review Manager v5.3 software. Results: After systematic review, 3 eligible RCTs were selected that included 4,104 patients; 2,687 comprised the treatment group and 1,417 the control group. No significant increase in RR for seizures was registered with the new anti-androgens compared to placebo (RR 1.96; 95% confidence interval [CI] 0.40–9.61). However, 2 trials excluded patients with risk factors or a history of seizures. There was also no significant increase RR for grade ≥3 seizures (RR 2.50; 95% CI 0.12–52.02). RR for suffering dizziness (any grade) was 1.57 (95% CI 1.07–2.32) with the new anti-androgens, but no significant differences were found in the other study regarding neuropsychiatric events or grade ≥3 events. Conclusions: New anti-androgens (i.e., enzalutamide, apalutamide, and darolutamide) are acceptably safe in terms of seizures and neuropsychiatric toxicity compared to placebo in patients with nmCRPC.

scholarly journals Overall survival and adverse events after treatment with darolutamide vs. apalutamide vs. enzalutamide for high-risk non-metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

2021 ◽  
Author(s):  
Mike Wenzel ◽  
Luigi Nocera ◽  
Claudia Collà Ruvolo ◽  
Christoph Würnschimmel ◽  
Zhe Tian ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Overall Survival ◽  
High Risk ◽  
Meta Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Pubmed Search ◽  
Grade 3 ◽  
Meta Analyses

Abstract Background The most recent overall survival (OS) and adverse event (AE) data have not been compared for the three guideline-recommended high-risk non-metastatic castration-resistant prostate cancer (nmCRPC) treatment alternatives. Methods We performed a systematic review and network meta-analysis focusing on OS and AE according to the most recent apalutamide, enzalutamide, and darolutamide reports. We systematically examined and compared apalutamide vs. enzalutamide vs. darolutamide efficacy and toxicity, relative to ADT according to PRISMA. We relied on PubMed search for most recent reports addressing prospective randomized trials with proven predefined OS benefit, relative to ADT: SPARTAN, PROSPER, and ARAMIS. OS represented the primary outcome and AEs represented secondary outcomes. Results Overall, data originated from 4117 observations made within the three trials that were analyzed. Regarding OS benefit relative to ADT, darolutamide ranked first, followed by enzalutamide and apalutamide, in that order. In the subgroup of PSA-doubling time (PSA-DT) ≤ 6 months patients, enzalutamide ranked first, followed by darolutamide and apalutamide in that order. Conversely, in the subgroup of PSA-DT 6–10 months patients, darolutamide ranked first, followed by apalutamide and enzalutamide, in that order. Regarding grade 3+ AEs, darolutamide was most favorable, followed by enzalutamide and apalutamide, in that order. Conclusion The current network meta-analysis suggests the highest OS efficacy and lowest grade 3+ toxicity for darolutamide. However, in the PSA-DT ≤ 6 months subgroup, the highest efficacy was recorded for enzalutamide. It is noteworthy that study design, study population, and follow-up duration represent some of the potentially critical differences that distinguish between the three studies and remained statistically unaccounted for using the network meta-analysis methodology. Those differences should be strongly considered in the interpretation of the current and any network meta-analyses.

scholarly journals Response and Toxicity to the Second Course of 3 Cycles of 177Lu-PSMA Therapy Every 4 Weeks in Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2489
Author(s):  
Sazan Rasul ◽  
Tim Wollenweber ◽  
Lucia Zisser ◽  
Elisabeth Kretschmer-Chott ◽  
Bernhard Grubmüller ◽  
...  
Keyword(s):  
Response Rate ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Radioligand Therapy ◽  
Free Survival ◽  
Castration Resistant ◽  
Kaplan Meier ◽  
Node Metastases ◽  
Grade 3

Background: We investigated the response rate and degree of toxicity of a second course of three cycles of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) every 4 weeks in mCRPC patients. Methods: Forty-three men (71.5 ± 6.6 years, median PSA 40.8 (0.87–1358 µg/L)) were studied. The response was based on the PSA level 4 weeks after the third cycle. The laboratory parameters before and one month after the last cycle were compared. Kaplan–Meier methods were used to estimate the progression-free survival (PFS) and overall survival (OS), and the Cox regression model was performed to find predictors of survival. Results: Twenty-six patients (60.5%) exhibited a PSA reduction (median PSA declined from 40.8 to 20.2, range 0.6–1926 µg/L, p = 0.002); 18 (42%) and 8 (19%) patients showed a PSA decline of ≥50% and ≥80%, respectively. The median OS and PFS were 136 and 31 weeks, respectively. The patients with only lymph node metastases survived longer (p = 0.02), whereas the patients with bone metastases had a shorter survival (p = 0.03). In the multivariate analysis, only the levels of PSA prior to the therapy remained significant for OS (p < 0.05, hazard ratio 2.43, 95% CI 1.01–5.87). The levels of hemoglobin (11.5 ± 1.7 g/dL vs. 11 ± 1.6 g/dL, p = 0.006) and platelets (208 ± 63 g/L vs. 185 ± 63 g/L, p = 0.002) significantly decreased one month after cycle three, though only two grade 3 anemia and one grade 3 thrombocytopenia were recorded. Conclusion: A further intensive PSMA-RLT course is well tolerated in mCRPC patients and associated with promising response rates and OS.

scholarly journals Tolerability of statin-based management of patients with a history of statin-associated muscle symptoms: protocol for a systematic review

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e052341
Author(s):  
Fanny Villoz ◽  
Christina Lyko ◽  
Cinzia Del Giovane ◽  
Nicolas Rodondi ◽  
Manuel R Blum
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Mean Difference ◽  
Control Group ◽  
Cochrane Central Register ◽  
Eligibility Criteria ◽  
Clinical Issue ◽  
Standard Data ◽  
Evaluation Approach ◽  
History Of

IntroductionStatin-associated muscle symptoms (SAMSs) are a major clinical issue in the primary and secondary prevention of cardiovascular events. Current guidelines advise various approaches mainly based on expert opinion. We will lead a systematic review and meta-analysis to explore the tolerability and acceptability and effectiveness of statin-based therapy management of patients with a history of SAMS. We aim to provide evidence on the tolerability and different strategies of statin-based management of patients with a history of SAMS.Methods and analysisWe will conduct a systematic review of randomised controlled trials (RCTs) and non-randomised studies with a control group. We will search in Data sources MEDLINE, EMBASE, Cochrane Central Register of Controlled Clinical Trials, Scopus, Clinicaltrials.gov and Proquest from inception until April 2021. Two independent reviewers will carry out the study selection based on eligibility criteria. We will extract data following a standard data collection form. The reviewers will use the Cochrane Collaboration’s tools and Newcastle-Ottawa Scale to appraise the study risk of bias. Our primary outcome will be tolerability and our secondary outcomes will be acceptability and effectiveness. We will conduct a qualitative analysis of all included studies. In addition, if sufficient and homogeneous data are available, we will conduct quantitative analysis. We will synthesise dichotomous data using OR with 95% CI and continuous outcomes by using mean difference or standardised mean difference (with 95% CI). We will determine heterogeneity visually with forest plots and quantitatively with I2 and Q-test. We will summarise the confidence in the quantitative estimate by using Grading of Recommendations Assessment, Development and Evaluation approach.Ethics and disseminationAs a systematic review of literature without collection of new clinical data, there will be no requirement for ethical approval. We will disseminate findings through peer-reviewed publications.PROSPERO registration numberCRD42020202619.

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.

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

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

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

Therapeutic efficacy of specific immunotherapy for glioma: a systematic review and meta-analysis

2018 ◽  
Vol 29 (4) ◽  
pp. 443-461 ◽  
Author(s):  
Sara Hanaei ◽  
Khashayar Afshari ◽  
Armin Hirbod-Mobarakeh ◽  
Bahram Mohajer ◽  
Delara Amir Dastmalchi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Overall Survival ◽  
Clinical Trials ◽  
Specific Immunotherapy ◽  
Data Extraction ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Control Group ◽  
Free Survival ◽  
Median Difference

Abstract Although different immunotherapeutic approaches have been developed for the treatment of glioma, there is a discrepancy between clinical trials limiting their approval as common treatment. So, the current systematic review and meta-analysis were conducted to assess survival and clinical response of specific immunotherapy in patients with glioma. Generally, seven databases were searched to find eligible studies. Controlled clinical trials investigating the efficacy of specific immunotherapy in glioma were found eligible. After data extraction and risk of bias assessment, the data were analyzed based on the level of heterogeneity. Overall, 25 articles with 2964 patients were included. Generally, mean overall survival did not statistically improve in immunotherapy [median difference=1.51; 95% confidence interval (CI)=−0.16–3.17; p=0.08]; however, it was 11.16 months higher in passive immunotherapy (95% CI=5.69–16.64; p<0.0001). One-year overall survival was significantly higher in immunotherapy groups [hazard ratio (HR)=0.69; 95% CI=0.52–0.92; p=0.01]. As the hazard rate in the immunotherapy approach was 0.83 of the control group, 2-year overall survival was significantly higher in immunotherapy (HR=0.83; 95% CI=0.69–0.99; p=0.04). Three-year overall survival was significantly higher in immunotherapy as well (HR=0.67; 95% CI=0.48–0.92; p=0.01). Overall, median progression-free survival was significantly higher in immunotherapy (standard median difference=0.323; 95% CI=0.110–0.536; p=0.003). However, 1-year progression-free survival was not remarkably different between immunotherapy and control groups (HR=0.94; 95% CI=0.74–1.18; p=0.59). Specific immunotherapy demonstrated remarkable improvement in survival of patients with glioma and could be a considerable choice of treatment in the future. Despite the current promising results, further high-quality randomized controlled trials are required to approve immunotherapeutic approaches as the standard of care and the front-line treatment for glioma.

scholarly journals Efficacy and Safety of Abiraterone Acetate and Enzalutamide for the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
ZhenHeng Wei ◽  
ChuXin Chen ◽  
BoWen Li ◽  
YongYue Li ◽  
Hong Gu
Keyword(s):  
Prostate Cancer ◽  
Systematic Review ◽  
Prostate Specific Antigen ◽  
Meta Analysis ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Efficacy And Safety ◽  
Castration Resistant Prostate Cancer ◽  
Randomized Controlled ◽  
Castration Resistant

ObjectiveThe androgen receptor-targeting drugs abiraterone acetate and enzalutamide have shown positive results as treatments for metastatic castration-resistant prostate cancer (mCRPC). Therefore, a meta-analysis was conducted to compare the efficacy and safety of abiraterone acetate and enzalutamide in patients with mCRPC.MethodsWe retrieved relevant articles from PubMed, Cochrane, and EMBASE published before December 31, 2020. Eleven articles were initially selected, and four phase III, double-blind, randomized controlled trials of abiraterone acetate and enzalutamide that involved 5199 patients with mCRPC were included. The end points were time to prostate-specific antigen progression (TTPP), according to the prostate-specific antigen working group criteria; overall survival (OS); and radiographic progression-free survival (rPFS).ResultsFour randomized, controlled clinical trials involving 5199 patients were included in this study. The results of the meta-analysis showed that compared with placebo alone, abiraterone significantly improved OS (HR=0.69, 95% CI: 0.60-0.8, P&lt;0.00001), rPFS (HR=0.64, 95% CI: 0.57-0.71, P &lt; 0.00001), and TTPP (HR=0.52, 95% CI: 0.45-0.59, P &lt; 0.00001) in patients with mCRPC. Compared with placebo, enzalutamide significantly improved OS (HR=0.67, 95% CI: 0.59-0.75, P&lt;0.00001), rPFS (HR=0.33, 95% CI: 0.29-0.37, P&lt; 0.00001), and TTPP (HR=0.19, 95% CI: 0.17-0.22, P &lt; 0.00001). An indirect comparison was performed to compare the efficacy of abiraterone and enzalutamide. The results showed that there was no significant difference between abiraterone and enzalutamide with regard to improving the OS of patients with mCRPC (HR=1.03, 95% CI: 0.854-1.242). Enzalutamide was superior to abiraterone with regard to improving rPFS in patients with mCRPC (HR=0.516, 95% CI: 0.438-0.608). With regard to improving TTPP, the efficacy of enzalutamide was better than that of abiraterone (HR=0.365, 95% CI: 0.303-0.441). In sAE, there was no difference between abiraterone and enzalutamide (P=0.21, I2 = 38%).ConclusionsCompared with placebo, both abiraterone and enzalutamide significantly prolonged OS, rPFS, and TTPP in patients with mCRPC. There was no difference in safety between abiraterone and enzalutamide. In addition, enzalutamide had better efficacy than abiraterone with regard to improving rPFS and TTPP but not OS, but the level of evidence was low. Therefore, a large direct comparison trial is needed to compare the efficacy of the two drugs.Systematic Review RegistrationPROSPERO, identifier (CRD42021226808)

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