abiraterone-acetate and Adenocarcinoma

Topics: Abiraterone Acetate; Adenocarcinoma; Adrenal Cortex Hormones; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Contraindications, Drug; COVID-19; Humans; Immunosuppressive Agents; Male; Meta-Analysis as Topic; Neoplasms, Hormone-Dependent; Oxygen; Pandemics; Practice Guidelines as Topic; Prospective Studies; Prostatic Neoplasms; Prostatic Neoplasms, Castration-Resistant; Randomized Controlled Trials as Topic; Respiration, Artificial; Risk; SARS-CoV-2

Für die Therapie des metastasierten kastrationsresistenten Prostatakarzinoms (mCRPC) stehen inzwischen mehrere moderne Wirkstoffe zur Verfügung. Sie verdrängen zunehmend die aufgrund mangelnder Alternativen lange Jahre üblichen sekundären Hormonmanipulationen, denn neuere Substanzen konnten - im Gegensatz zu den konventionellen antihormonellen Therapien - das Überleben in Phase-III-Studien verlängern. So ist der Beginn der mCRPC-Therapie gemäß Leitlinie der European Association of Urology in den letzten Jahren im Krankheitsverlauf nach vorne gerückt. Für den Androgen-Biosynthese-Inhibitor Abirateronacetat, einen dieser modernen Wirkstoffe, liefern mehrere Analysen zusätzliche Hinweise, wann die Behandlung begonnen werden könnte.

Topics: Abiraterone Acetate; Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Evidence-Based Medicine; Humans; Male; Medical Oncology; Practice Guidelines as Topic; Prostatic Neoplasms, Castration-Resistant; Secondary Prevention; Treatment Outcome

Abirateronacetat, das in Kombination mit Prednison/Prednisolon verabreicht wird, spielt eine wichtige Rolle in der Therapie des metastasierten kastrationsresistenten Prostatakarzinoms. Im Folgenden wurden besondere Aspekte der Therapie im klinischen Alltag zusammengestellt. Sie betreffen unter anderem die Dosierung - auch vor dem Hintergrund der Markteinführung einer neuen Formulierung von Abirateronacetat. Hinzu kommt die Verträglichkeit, vor allem in Bezug auf kardiovaskuläre und Kortikoid-bedingte Nebenwirkungen. Des Weiteren werden Kriterien genannt, nach denen die Therapie nicht zu früh umgestellt werden sollte.

Topics: Abiraterone Acetate; Adenocarcinoma; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Europe; Evidence-Based Medicine; Humans; Male; Prednisolone; Prostatic Neoplasms, Castration-Resistant; Treatment Outcome

Topics: Abiraterone Acetate; Adenocarcinoma; Androgen Antagonists; Androgens; Androstadienes; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase III as Topic; Disease-Free Survival; Docetaxel; Enzyme Inhibitors; Humans; Male; Molecular Targeted Therapy; Multicenter Studies as Topic; Neoplasm Proteins; Neoplasms, Hormone-Dependent; Prednisone; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Receptors, Androgen; Steroid 17-alpha-Hydroxylase; Survival Rate; Taxoids

To evaluate the potential benefit of curative radiotherapy (RT) to the primary tumor in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone.. The clinical parameters of 106 mCRPC patients treated with abiraterone were retrospectively evaluated. Patients were either oligometastatic (≤5 metastases) at diagnosis or became oligometastatic after the systemic treatment was analyzed. Local RT to the primary tumor and pelvic lymphatics was delivered in 44 patients (41%), and 62 patients (59%) did not have RT to the primary tumor. After propensity match analysis, a total of 92 patients were analyzed.. Median follow-up time was 14.2 months (range: 2.3-54.9 months). Median overall survival (OS) was higher in patients treated with local RT to the primary tumor than in those treated without local RT with borderline significance (24.1 vs. 21.4 months; p = 0.08). Local RT to the prostate and pelvic lymphatics significantly diminished the local recurrence rate (16 patients, 31% vs. 2 patients, 5%; p = 0.003). In multivariate analysis, the prostate specific antigen (PSA) response ≥50% of the baseline obtained 3 weeks after abiraterone therapy was the only significant prognostic factor for better OS and progression-free survival (PFS). Patients treated with primary RT to the prostate had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.. Local prostate RT significantly improved OS and local control in mCRPC patients treated with abiraterone. The patients treated with primary RT had significantly less progression under abiraterone and a longer abiraterone period than those treated without local prostate RT.

Topics: Abiraterone Acetate; Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Combined Modality Therapy; Drug Administration Schedule; Follow-Up Studies; Humans; Lymphatic Irradiation; Male; Middle Aged; Neoplasm Staging; Prednisone; Prognosis; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Radiotherapy Dosage; Radiotherapy, Adjuvant; Retrospective Studies

Testosterone suppression is the standard treatment for advanced prostate cancer, and it is associated with side-effects that impair patients' quality of life, like sexual dysfunction, osteoporosis, weight gain, and increased cardiovascular risk. We hypothesized that abiraterone acetate with prednisone (AAP) and apalutamide, alone or in combination, can be an effective hormonal therapy also possibly decreasing castration-associated side effects.. Phase II, open-label, randomized, efficacy trial of abiraterone acetate plus prednisone (AAP) and Androgen Deprivation Therapy (ADT) versus apalutamide versus the combination of AAP (without ADT) and apalutamide. Key eligibility criteria are confirmed prostate adenocarcinoma; biochemical relapse after definitive treatment (PSA ≥ 4 ng/ml and doubling time less than 10 months, or PSA ≥ 20 ng/ml); newly diagnosed locally advanced or metastatic prostate cancer; asymptomatic to moderately symptomatic regarding bone symptoms. Patients with other histology besides adenocarcinoma or previous use of hormonal therapy or chemotherapy were excluded.. There is an urgent need to study and validate regimens such as new hormonal agents that may add benefit to castration with an acceptable safety profile. We aim to evaluate if apalutamide in monotherapy or in combination with AAP is an effective and safety hormonal treatment that can spare patients of androgen deprivation therapy.. This trial was registered in ClinicalTrials.gov on October 16, 2017, under Identifier: NCT02867020.

Topics: Abiraterone Acetate; Adenocarcinoma; Androgen Receptor Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Goserelin; Humans; Male; Patient Reported Outcome Measures; Prednisone; Prostatic Neoplasms, Castration-Resistant; Quality of Life; Testosterone; Thiohydantoins; Treatment Outcome

Men with metastatic prostate cancer who have a poor response to initial androgen-deprivation therapy (ADT), as reflected by a prostate-specific antigen (PSA) level higher than 4.0 ng/mL after 7 months of ADT, have a poor prognosis, based on historical controls.. To determine the efficacy of abiraterone acetate with prednisone in these high-risk patients with a suboptimal response to hormonal induction.. A phase 2 single-arm study was conducted through the National Clinical Trials Network-Southwest Oncology Group. Eligible patients had metastatic prostate cancer and a PSA level higher than 4.0 ng/mL between 6 and 12 months after starting ADT. The PSA level could be rising or falling at the time of enrollment, but had to be higher than 4.0 ng/mL. No previous chemotherapy or secondary hormonal therapies were allowed, except in patients receiving a standard, first-generation antiandrogen agent with a falling PSA level at the time of enrollment; this therapy was continued in this cohort. Abiraterone acetate, 1000 mg, once daily with prednisone, 5 mg, twice daily was administered to all participants. A total of 41 men were enrolled between the trial's activation on August 9, 2011, and closure on August 1, 2013. Data analysis was conducted from March 21 to November 29, 2016.. Abiraterone acetate, 1000 mg, once daily by mouth with prednisone, 5 mg, by mouth twice daily.. The primary end point was a PSA level of 0.2 ng/mL or lower within 12 months of starting abiraterone acetate plus prednisone. A partial response (PR) was a secondary end point, defined as a PSA level reduction to lower than 4.0 ng/mL but higher than 0.2 ng/mL.. Of the 41 men enrolled, 1 did not receive any protocol treatment and was excluded from analysis. The median (range) age of the 40 participants was 66 (39-85) years. Five (13%) patients achieved a PSA level of 0.2 ng/mL or lower (95% CI, 4%-27%). Thirteen (33%) additional patients achieved a partial response, with a reduction in the PSA level to lower than 4.0 ng/mL but higher than 0.2 ng/mL. Sixteen (40%) patients had no PSA response and 6 (15%) were not assessable and assumed to be nonresponders. The median progression-free survival was 17.5 months (95% CI, 8.6-25.0 months) and the median overall survival was 25.8 months (95% CI, 15.7-25.8 months). There was 1 incident each of grade 4 adverse events of alanine aminotransferase level elevation and rectal hemorrhage. Eleven patients reported grade 3 adverse events.. This study did not reach its prescribed level of 6 PSA responses of 0.2 ng/mL or lower, although 5 responses were observed. The overall survival and progression-free survival rates observed in this trial are encouraging compared with historical controls. The therapy was generally well tolerated, without any clear signal of any unexpected adverse effects.

Topics: Abiraterone Acetate; Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Humans; Kallikreins; Male; Middle Aged; Prednisone; Prostate-Specific Antigen; Prostatic Neoplasms; Survival Analysis; Time Factors; Treatment Outcome; United States

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. Here we report on the impact of abiraterone therapy on the health-related quality of life (HRQoL) observed during this trial, assessed using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire.. All analyses were conducted using prespecified criteria for clinically meaningful improvement and deterioration in FACT-P total score as well as subscale scores; all respective thresholds were defined using an accepted methodology. Improvement was assessed only in patients with clinically significant functional status impairment at baseline.. Significant improvements in the FACT-P total score were observed in 48% of patients receiving abiraterone versus 32% of patients receiving prednisone (p < 0.0001). Also, the median time to deterioration in FACT-P total score was longer (p < 0.0001) in patients receiving abiraterone (59.9 weeks versus 36.1 weeks). Similar differences were observed in all FACT-P subscales, with the exception of the social/family well-being domain. Median time to improvement in the physical well-being domain and the trial outcome index was significantly shorter (p < 0.01) with abiraterone when compared with the prednisone arm.. The previously demonstrated survival benefit for abiraterone is accompanied by improvements in patient-reported HRQoL and a significant delay in HRQoL deterioration when compared with prednisone.

Topics: Abiraterone Acetate; Adenocarcinoma; Androstadienes; Antineoplastic Agents; Chemotherapy, Adjuvant; Docetaxel; Humans; Male; Neoplasm Metastasis; Orchiectomy; Placebos; Prostatic Neoplasms; Quality of Life; Surveys and Questionnaires; Taxoids; Treatment Failure

Abiraterone became a standard hormonal therapy for patients with metastatic castration-resistance prostate cancer (mCRPC). However, patients may experience primary resistance to treatment. To date, few predictive biomarkers of efficacy have been identified. Our aim was to investigate the association between the single nucleotide polymorphism (SNP) c.-362T>C in the CYP17A1 gene, and clinical outcome in mCRPC patients treated with abiraterone.. mCRPC patients candidate to receive abiraterone were enrolled in the present retrospective pharmacogenetic study. Based on a literature selection, CYP17A1 rs2486758 (c.-362T > C) was selected and analysed by real-time PCR on genomic DNA extracted from whole blood. Univariate analysis was performed to test the association between the SNP and treatment-related clinical outcomes.. Sixty mCRPC patients were enrolled in the present study. Patients carrying the mutant CYP17A1 c.-362CT/CC genotypes showed a shorter median progression-free survival (PFS) and prostate-specific antigen-PFS (PSA-PFS) compared to patients carrying the TT genotype (10.7 vs 14.2 months and 8 vs 16 months, respectively; p = 0.04). No association between the selected SNP and the overall survival was found.. These findings suggest an association between CYP17A1 c.-362T>C polymorphism and poorer clinical outcome with abiraterone for mCRPC patients. However, further validations on larger cohort of patients are needed to confirm its role as a predictive biomarker for abiraterone resistance.

Topics: Abiraterone Acetate; Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease Progression; Drug Resistance, Neoplasm; Humans; Kallikreins; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Grading; Polymorphism, Single Nucleotide; Prognosis; Progression-Free Survival; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies; Steroid 17-alpha-Hydroxylase

Clinical studies have demonstrated the benefits of abiraterone acetate + prednisone (AAP) and enzalutamide (ENZ) in significantly improving survival among metastatic castration-resistant prostate cancer (mCRPC) patients. However, evidence regarding patient's real-world experience, particularly with respect to fatigue, treatment satisfaction and health-related quality of life (HRQoL) is limited. Interviews were initially conducted with patients (n = 38) and carers (n = 12) to elicit qualitative data regarding their experiences. Findings informed the design of a quantitative, multinational online survey of mCRPC patients (n = 152) receiving AAP or ENZ. Participants completed validated questionnaires assessing fatigue (Brief Fatigue Inventory), treatment satisfaction (Cancer Therapy Satisfaction Questionnaire) and HRQoL (EuroQol-5-Dimensions). Results indicated that patients were generally satisfied with these therapies, more specifically with reductions in prostate-specific antigen levels and extended survival. Fatigue was commonly linked to poor HRQoL and responses indicated that significantly fewer patients in the AAP group reported feeling usually tired or fatigued in the last week compared to the ENZ group (33% vs. 55%, p = 0.006 respectively). Findings highlight the benefit of AAP and ENZ in promoting the "quality" of extended survival. That fatigue was lower among patients receiving AAP may be important for informing treatment decisions. Further research is needed to gain deeper insights.

Topics: Abiraterone Acetate; Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Fatigue; Health Status; Humans; Male; Middle Aged; Neoplasm Metastasis; Nitriles; Patient Satisfaction; Phenylthiohydantoin; Prednisone; Prostatic Neoplasms, Castration-Resistant; Qualitative Research; Quality of Life

To describe the patterns of second-line treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) after docetaxel treatment in a Spanish population, to identify the factors associated with those patterns, and to compare the efficacy and safety of the treatments most frequently administered.. Observational, prospective study conducted in patients with histologically or cytologically confirmed prostate adenocarcinoma; documented metastatic castration-resistant disease; progression after first-line, docetaxel-based chemotherapy with or without other agents.. Of the 150 patients recruited into the study, 100 patients were prescribed abiraterone acetate plus prednisone (AAP), 44 patients received cabazitaxel plus prednisone (CP), and 6 patients received other treatments. Age (odds ratio [OR] 1.06, 95% [confidence interval] CI 1.01 to 1.11) and not elevated lactate dehydrogenase (LDH) levels (OR 0.33, 95% CI 0.14 to 0.76) were independently associated with the administration of AAP. Treatment with AAP was associated with significantly longer clinical/radiographic progression-free survival (hazard ratio [HR] 0.57, 95% CI 0.38 to 0.85) and overall survival (OS; HR 0.40, 95% CI 0.21 to 0.76) compared to CP, while no significant differences between the treatments were found regarding biochemical progression-free survival (PFS; HR 0.78 [95% CI 0.49 to 1.24]). However, in a post-hoc Cox regression analysis adjusted for potential confounders there were not differences between AAP and CP in any of the time-to-event outcomes, including overall survival. We observed no new safety signals related to either regimen.. Second-line AAP for patients with mCRPC is the most common treatment strategy after progression with a docetaxel-based regimen. When controlling for potential confounders, patients receiving this treatment showed no differences in PFS and OS in comparison to those receiving CP, although these latter results should be confirmed in randomized controlled trials.

Topics: Abiraterone Acetate; Adenocarcinoma; Age Factors; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Docetaxel; Humans; Kaplan-Meier Estimate; L-Lactate Dehydrogenase; Male; Middle Aged; Multivariate Analysis; Pain; Prednisone; Progression-Free Survival; Proportional Hazards Models; Prospective Studies; Prostatic Neoplasms, Castration-Resistant; Spain; Taxoids; Treatment Outcome

Topics: Abiraterone Acetate; Adenocarcinoma; Adrenal Cortex Hormones; Aged; Antineoplastic Agents, Hormonal; Bone Neoplasms; Chlorpheniramine; Desensitization, Immunologic; Dexamethasone; Drug Administration Schedule; Histamine Antagonists; Humans; Male; Prostatic Neoplasms, Castration-Resistant; Urticaria

To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).. We conducted an analysis in 115 chemotherapy-naïve mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment. Comparative t-test was used to evaluate the serial changes of serum NED markers during AA treatment and univariate and multivariate analyses were performed to test the influence of AA treatment on NED.. Serum CgA were NSE were evaluated to be above the upper limit of normal (ULN) in 56 (48.7%) and 29 (25.2%) patients before chemotherapy. In 34 patients with serial evaluation, serum CgA level of 14 patients and NSE of 14 patients increased after the failure of AA treatment. There was no significant difference of NED markers (CgA or NSE variation (P = 0.243) between at baseline and after the failure of AA treatment. Compared with the CgA elevation group in the first 6 months of AA treatment and baseline supranormal CgA group, the CgA decline group, and baseline normal CgA group has a much longer median PSA PFS (14.34 vs 10.00 months, P < 0.001, and 14.23 vs 10.30 months, P = 0.02) and rPFS, respectively (18.33 vs 11.37 months, P < 0.001, and 17.10 vs 12.07 months, P = 0.03). In logistic univariate analysis, AA treatment and its duration were not independent factors influencing NED.. We hypothesized that AA might not significantly lead to progression of NED of mCRPC in general. Furthermore, we found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment. Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.

Topics: Abiraterone Acetate; Adenocarcinoma; Aged; Antineoplastic Agents; Biomarkers; China; Chromogranin A; Drug Monitoring; Humans; Male; Middle Aged; Neurosecretion; Prostate; Prostate-Specific Antigen; Prostatic Neoplasms, Castration-Resistant; Retrospective Studies

We evaluated the association of PSA and androgen receptor splice variant-7 (AR-V7) transcript levels in patients' blood with time to treatment failure (TTF) and overall survival (OS) with abiraterone acetate and/or enzalutamide treatment in castration-resistant prostate cancer (CRPC) patients.. RNA levels of AR-V7 and PSA in peripheral blood collected before treatment were quantified using droplet digital-PCR in retrospective cohorts treated with abiraterone acetate (N = 81) or enzalutamide (N = 51) for CRPC. Multivariable Cox regression adjusted for known prognostic factors was used for analyses.. PSA transcripts were detected in 57% of abiraterone acetate-treated patients and in 63% of enzalutamide-treated patients. PSA-positive patients had a shorter TTF than PSA-negative patients [adjusted HR = 2.27 (95% confidence interval (CI) 1.26-4.10) and 2.60 (95% CI, 1.19-5.69); P = 0.006 and 0.017 in abiraterone acetate and enzalutamide cohorts, respectively]. Patients with a higher-AR-V7 transcript level had a shorter TTF with abiraterone acetate and enzalutamide in univariate analysis (median 8.0 months vs. 15.6 months, P = 0.046 in abiraterone acetate-cohort and 3.6 months vs. 5.6 months; P = 0.050 in enzalutamide cohort). In multivariable models, the association with TTF remained significant in the enzalutamide cohort (adjusted HR = 2.02; 95% CI, 1.01-4.05; P = 0.048), but statistically insignificant in the abiraterone acetate cohort. In both cohorts, we observed potential prognostic value of both PSA and AR-V7 RNA expression on OS; patients with detectable PSA transcripts and high AR-V7 predicted the poorest OS.. PSA and AR-V7 transcripts in blood potentially serve as biomarkers predicting TTF and OS with abiraterone acetate or enzalutamide treatment. If validated prospectively, their detection could be facilitated without isolation of circulating tumor cells. Clin Cancer Res; 23(3); 726-34. ©2016 AACR.

Topics: Abiraterone Acetate; Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Benzamides; Biomarkers, Tumor; Humans; Kallikreins; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasms, Hormone-Dependent; Nitriles; Phenylthiohydantoin; Prognosis; Proportional Hazards Models; Prostate-Specific Antigen; Prostatic Neoplasms; Protein Isoforms; Receptors, Androgen; Retrospective Studies; RNA, Messenger; RNA, Neoplasm; Steroid 17-alpha-Hydroxylase