BACKGROUND: Preclinical studies and results of a phase 2 trial of abiraterone and olaparib suggest a combined antitumor effect when the poly(adenosine diphosphate[ADP]-ribose) polymerase inhibitor olaparib is combined with next-generation hormonal agent abiraterone to treat metastatic castration-resistant prostate cancer (mCRPC). METHODS: We conducted a double-blind, phase 3 trial of abiraterone and olaparib versus abiraterone and placebo in patients with mCRPC in the first-line setting. Patients were enrolled regardless of homologous recombination repair gene mutation (HRRm) status. HRRm status was determined following enrollment by tumor tissue and circulating tumor DNA tests. Patients were randomly assigned (1:1) to receive abiraterone (1000 mg once daily) plus prednisone or prednisolone with either olaparib (300 mg twice daily) or placebo. The primary end point was imaging-based progression-free survival (ibPFS) by investigator assessment. Overall survival was among the secondary end points. RESULTS: At this planned primary analysis at the first data cutoff, median ibPFS was significantly longer in the abiraterone and olaparib arm than in the abiraterone and placebo arm (24.8 vs. 16.6 months; hazard ratio, 0.66; 95% confidence interval [CI], 0.54 to 0.81; P<0.001) and was consistent with blinded independent central review (hazard ratio, 0.61; 95% CI, 0.49 to 0.74). At this data cutoff, overall survival data were immature (28.6% maturity; hazard ratio, 0.86; 95% CI, 0.66 to 1.12; P=0.29). The safety profile of olaparib and abiraterone was consistent with the known safety profiles of the individual drugs. The most common adverse events in the abiraterone and olaparib arm were anemia, fatigue/asthenia, and nausea. CONCLUSIONS: At primary analysis at this first data cutoff, abiraterone combined with olaparib significantly prolonged ibPFS compared with abiraterone and placebo as first-line treatment for patients with mCRPC enrolled irrespective of HRRm status. (Funded by AstraZeneca and Merck Sharp & Dohme, LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA; ClinicalTrials.gov number, NCT03732820.)

• MeSH
• androsteny MeSH
• ftalaziny * MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   MeSH
• piperaziny * MeSH
• protokoly protinádorové kombinované chemoterapie terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• androsteny MeSH
• ftalaziny * MeSH
• olaparib MeSH Prohlížeč
• piperaziny * MeSH

Background: The aim of the present study was to examine the efficacy of carboplatin in combination with paclitaxel in patients with metastatic castration-resistant prostate cancer pretreated with multiple regimens including docetaxel and androgen receptor-targeted agents. Methods: Clinical data from patients treated with carboplatin plus paclitaxel were collected retrospectively from a single institution. Results: 43 patients with metastatic castration-resistant prostate cancer were identified. Median number of cycles was ten (range: 1 to 23), prostate-specific antigen response was observed in 18 (42%) patients, median progression-free survival was 115 days and median overall survival was 8.1 months. Conclusion: Combination chemotherapy using taxane with carboplatin is an effective and well-tolerated therapy in heavily pretreated patients with metastatic castration-resistant prostate cancer.

The prognosis of metastatic castration-resistant prostate cancer (mCRPC) refractory to docetaxel is poor, with only limited guidance on the optimal treatment strategy. We reviewed patients with mCRPC treated with weekly carboplatin/paclitaxel in a single institution, analyzing their prostate-specific antigen (PSA) response, progression-free survival, treatment duration and overall survival (OS). Potential predictive biomarkers and tolerability were evaluated. 43 patients treated between 2012 and 2020 were identified, including 40 refractory to docetaxel. 19 (44%) had received two prior chemotherapy regimens and 38 (88%) were pretreated with androgen receptor-targeted agents; 18 patients (42%) had bone-only disease and 16 (37%) had visceral disease. Median number of cycles was ten (range: 1 to 23), PSA response (>50% decline) was observed in 18 patients (42%), median progression-free survival was 115 days and median OS was 8.36 months. 11 patients (26%) experienced reversible grade 3 or 4 toxicity, two (5%) had febrile neutropenia, and no lethal adverse events were observed. The prognostic role for OS was confirmed for PSA response, higher line of therapy, pretreatment with enzalutamide, longer response to androgen-deprivation therapy and response to docetaxel. In conclusion, combination chemotherapy with carboplatin/paclitaxel is a viable, effective and well-tolerated therapy in heavily pretreated patients with mCRPC, but should be validated in a prospective trial.

• Klíčová slova
• ARTA, CRPC, biomarkers, carboplatin, castration resistant, chemotherapy, docetaxel-refractory, paclitaxel, prostate cancer, taxane,
• MeSH
• docetaxel terapeutické užití   MeSH
• karboplatina terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * patologie   MeSH
• paclitaxel * terapeutické užití   MeSH
• prostatický specifický antigen terapeutické užití   MeSH
• protokoly protinádorové kombinované chemoterapie škodlivé účinky   MeSH
• retrospektivní studie MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• docetaxel MeSH
• karboplatina MeSH
• paclitaxel * MeSH
• prostatický specifický antigen MeSH

BACKGROUND: The management of metastatic castration-resistant prostate cancer involves second-generation antiandrogen therapy, including enzalutamide. The recommended dose of 160mg/day is sometimes difficult to use in elderly patients because of the burden of comorbidities. The usefulness of a low effective dose remains unclear. METHODS: We report the first ever patient, now aged 87 years, who had progressing prostate cancer and was treated at 25% of the recommended dose for over 4 years. RESULTS: The most striking observation is that nothing extraordinary happened. The disease responded without dramatic toxicities. His follow-up has been serene on both aspects of prostate cancer and general health. CONCLUSION: Cautious dosage can have a long-lasting favorable impact in the elderly patient.

• Klíčová slova
• castration-resistant, enzalutamide, prostate cancer, prostatic neoplasms, reduced-dose drug use, treatment efficacy, treatment outcomes,
• MeSH
• benzamidy aplikace a dávkování   MeSH
• fenylthiohydantoin aplikace a dávkování   MeSH
• kalikreiny krev   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci krev   farmakoterapie   patologie   radioterapie   MeSH
• nitrily aplikace a dávkování   MeSH
• prostatektomie MeSH
• prostatický specifický antigen krev   MeSH
• protinádorové látky aplikace a dávkování   MeSH
• senioři nad 80 let MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• benzamidy MeSH
• enzalutamide MeSH Prohlížeč
• fenylthiohydantoin MeSH
• kalikreiny MeSH
• KLK3 protein, human MeSH Prohlížeč
• nitrily MeSH
• prostatický specifický antigen MeSH
• protinádorové látky MeSH

INTRODUCTION: This systematic review and meta-analysis aimed to assess the prognostic value of testosterone in patients with castration-resistant prostate cancer (CRPC). MATERIALS AND METHODS: PubMed, Web of Science, and Scopus databases were systematically searched until December 2019, according to the Preferred Reporting Items for Systemic Review and Meta-analysis statement. The endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: We identified 11 articles with 4206 patients for systematic review and nine articles with 4136 patients for meta-analysis. Higher testosterone levels were significantly associated with better OS (pooled HR 0.74, 95% CI 0.58-0.95) and better PFS (pooled HR 0.51, 95% CI 0.30-0.87). Subgroup analyses based on the treatment type revealed that higher testosterone levels were significantly associated with better OS in CRPC patients treated with androgen receptor-targeted agents (ARTAs) (pooled HR 0.64, 95% CI 0.55-0.75), but not in those treated with chemotherapy (pooled HR 0.78, 95% CI 0.53-1.14). CONCLUSION: This meta-analysis demonstrated that the PFS and OS were significantly greater in patients with CRPC in those with higher testosterone levels than that of those with lower testosterone levels. In the subgroup analyses, lower testosterone levels were a consistently poor prognostic factor for OS in patients treated with ARTAs, but not in those treated with chemotherapy. Therefore, higher testosterone levels could be a useful biomarker to identify patient subgroups in which ARTAs should be preferentially recommended in the CRPC setting.

• Klíčová slova
• Androgen receptor-targeted agents, Castration-resistant, Meta-analysis, Prostate cancer, Testosterone,
• MeSH
• androgenní receptory metabolismus   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci krev   farmakoterapie   mortalita   MeSH
• prognóza MeSH
• testosteron krev   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• androgenní receptory MeSH
• AR protein, human MeSH Prohlížeč
• testosteron MeSH

BACKGROUND: Non-metastatic castration-refractory prostate cancer (nmCRPC) is defined by increasing serum prostate specific antigen (PSA) levels despite androgen deprivation therapy in the absence of metastases on standard imaging methods including CT of the chest, abdomen and pelvis, and bone scan. Patients with nmCRPC and short PSA doubling time (PSAdt) are at high risk of developing early metastatic disease. OBJECTIVES: The objective of this review is to summarize current data on the treatment of nmCRPC. The current data support the efficacy of three novel androgen receptor targeted agents (ARTA), darolutamide, apalutamide and enzalutamide. CONCLUSIONS: The design and eligibility criteria of the three key studies with darolutamide, apalutamide and enzalutamide were similar. Patients were required to have a PSAdt.

• Klíčová slova
• androgen antagonists, antineoplastic agents, castration-refractory prostate cancer, drug toxicity, survival,
• MeSH
• androgenní receptory chemie   MeSH
• antagonisté androgenů terapeutické užití   MeSH
• cílená molekulární terapie metody   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci farmakoterapie   metabolismus   patologie   MeSH
• protinádorové látky terapeutické užití   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• androgenní receptory MeSH
• antagonisté androgenů MeSH
• AR protein, human MeSH Prohlížeč
• protinádorové látky MeSH

BACKGROUND: The evaluation of treatment outcomes and toxicity in patients with metastatic castration-resistant prostate cancer (mCRPC) treated by enzalutamide or abiraterone after previous docetaxel. PATIENTS AND METHODS: We analyzed 66 patients with mCRPC treated by enzalutamide (55 patients) or abiraterone (11 patients) after previous therapy with docetaxel. The median follow-up was 31.2 months. Enzalutamide and abiraterone were administered in daily doses of 160 mg and 1,000 mg per day, respectively. The progression free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier analysis. The prognostic influence of the factors on OS was evaluated by regression analysis. RESULTS: The progression was observed in 55 (83%) patients, and mPFS was 12.1 (95% CI 7.7-16.4) months. In total, 43 patients died, and he median OS was 21.9 (95% CI 12.2-31.7) months. In the regression analysis, we observed statistical favorable influence of the following factors on OS: PSA decrease ≥ 50%, in patients with early decrease of prostatic specific antigen (PSA) ≥ 50% in 3 months after initiation of enzalutamide or abiraterone treatment, in patients with visceral metastatic sites, in patients treated with only one regimen of previous chemotherapy and in those without anemia. We observed the toxicity grades 3-4 in 45.5% and 36.3% patients treated with enzalutamide and abiraterone, respectively. CONCLUSION: Our analysis demonstrated efficacy and good tolerance in patients with mCRPC treated with enzalutamide and abiraterone after previous docetaxel therapy.

• Klíčová slova
• Chemotherapy, abiraterone, androgen receptor, castration-resistant prostate cancer, chemother­apy, enzalutamide, metastases, neoplasm metastasis, targeted therapy,
• MeSH
• docetaxel MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   MeSH
• prostatický specifický antigen MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• docetaxel MeSH
• enzalutamide MeSH Prohlížeč
• prostatický specifický antigen MeSH

BACKGROUND: The PROpel study (NCT03732820) demonstrated a statistically significant progression-free survival benefit with olaparib plus abiraterone versus placebo plus abiraterone in the first-line metastatic castration-resistant prostate cancer (mCRPC) setting, irrespective of homologous recombination repair mutation status. OBJECTIVE: We report additional safety analyses from PROpel to increase clinical understanding of the adverse-event (AE) profiles of olaparib plus abiraterone versus placebo plus abiraterone. DESIGN, SETTING, AND PARTICIPANTS: A randomised (1:1), double-blind, placebo-controlled trial was conducted at 126 centres in 17 countries (October 2018-January 2020). Patients had mCRPC and no prior systemic mCRPC treatment. INTERVENTION: Olaparib (300 mg bid) or placebo with abiraterone (1000 mg od) plus prednisone/prednisolone (5 mg bid). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The data cut-off date was July 30, 2021. Safety was assessed by AE reporting (Common Terminology Criteria for Adverse Events v4.03) and analysed descriptively. RESULTS AND LIMITATIONS: The most common AEs (all grades) for olaparib plus abiraterone versus placebo plus abiraterone were anaemia (46.0% vs 16.4%), nausea (28.1% vs 12.6%), and fatigue (27.9% vs 18.9%). Grade ≥3 anaemia occurred in 15.1% versus 3.3% of patients in the olaparib plus abiraterone versus placebo plus abiraterone arm. The incidences of the most common AEs for olaparib plus abiraterone peaked early, within 2 mo, and were managed typically by dose modifications or standard medical practice. Overall, 13.8% versus 7.8% of patients discontinued treatment with olaparib plus abiraterone versus placebo plus abiraterone because of an AE; 3.8% versus 0.8% of patients discontinued because of anaemia. More venous thromboembolism events were observed in the olaparib plus abiraterone arm (any grade, 7.3%; grade ≥3, 6.8%) than in the placebo plus abiraterone arm (any grade, 3.3%; grade ≥3, 2.0%), most commonly pulmonary embolism (6.5% vs 1.8% for olaparib plus abiraterone vs placebo plus abiraterone). CONCLUSIONS: Olaparib plus abiraterone has a manageable and predictable safety profile. PATIENT SUMMARY: The PROpel trial showed that in patients who had not received any previous treatment for metastatic castration-resistant prostate cancer, olaparib combined with abiraterone was more effective in delaying progression of the disease than abiraterone alone. Most side effects caused by combining olaparib with abiraterone could be managed with supportive care methods, by pausing olaparib administration for a short period of time and/or by reducing the dose of olaparib.

• Klíčová slova
• Abiraterone, Metastatic castration-resistant prostate cancer, Olaparib, PROpel, Tolerability,
• MeSH
• androsteny * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• dvojitá slepá metoda MeSH
• ftalaziny * terapeutické užití   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory prostaty rezistentní na kastraci * farmakoterapie   patologie   MeSH
• piperaziny * terapeutické užití   aplikace a dávkování   škodlivé účinky   MeSH
• protokoly protinádorové kombinované chemoterapie * terapeutické užití   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• abiraterone MeSH Prohlížeč
• androsteny * MeSH
• ftalaziny * MeSH
• olaparib MeSH Prohlížeč
• piperaziny * MeSH

BACKGROUND: Investigation remains incomplete regarding potential variations in the effect of androgen receptor pathway inhibitors, including apalutamide, based on baseline tumor burden in patients with metastatic castration-sensitive prostate cancer (mCSPC). METHODS: The authors analyzed individual participant-level data from 1052 patients with mCSPC who were randomized in the TITAN trial (apalutamide vs. placebo, both with androgen-deprivation therapy). Outcomes included radiographic progression-free survival (PFS), second PFS (PFS2), and overall survival (OS). Multivariable Cox proportional hazards regression models, with and without restricted cubic splines, were used to determine the association between apalutamide benefit and bone metastasis count or visceral metastasis. Subgroup treatment effects were quantified based on inverse probability of treatment weighting-adjusted hazard ratios (HRs). RESULTS: Analysis using restricted cubic splines indicated that apalutamide provided less benefit for PFS2 and OS in patients with fewer bone metastases. The authors also found evidence of a heterogeneous effect of apalutamide on PFS2 and OS between patients with two or less bone metastases and those with three or more bone metastases. In patients who had two or less bone metastases, there was no evidence of a benefit from apalutamide for radiographic PFS (HR, 0.65; 95% confidence interval [CI], 0.35-1.22), PFS2 (HR, 1.18; 95% CI, 0.66-2.12), or OS (HR, 1.05; 95% CI, 0.60-1.83). No evidence of an association was noted between visceral metastasis and apalutamide benefit. CONCLUSIONS: The addition of apalutamide to androgen-deprivation therapy may provide less benefit in patients with mCSPC who have fewer bone metastases. Counting baseline bone metastases may help identify optimal candidates for apalutamide treatment of mCSPC. CLINICAL TRIALS REGISTRATION: NCT02489318 PLAIN LANGUAGE SUMMARY: In an analysis of individual participant data from a trial (the TITAN trial) in patients with metastatic (spreading) castration-sensitive prostate cancer, treatment intensification based on the addition new drugs to standard androgen-deprivation therapy (ADT) was analyzed and compared with the effects in patients who received only standard ADT. Compared with ADT alone, the survival benefit of adding the new drug apalutamide to standard ADT varied according to the number of bone metastases, but no association was observed between the spread of cancer to soft tissues and organs and a survival benefit from adding apalutamide. The results indicate that counting the number of bone metastases may help identify which patients with metastatic castration-sensitive prostate cancer are optimal candidates for treatment intensification with the addition of apalutamide to standard ADT.

• Klíčová slova
• apalutamide, castration‐sensitive prostate cancer, heterogeneity in treatment effect, prostate cancer,
• MeSH
• antagonisté androgenních receptorů terapeutické užití   MeSH
• antagonisté androgenů terapeutické užití   MeSH
• doba přežití bez progrese choroby MeSH
• lidé středního věku MeSH
• lidé MeSH
• metastázy nádorů MeSH
• nádory kostí sekundární   farmakoterapie   MeSH
• nádory prostaty rezistentní na kastraci farmakoterapie   patologie   mortalita   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• thiohydantoiny * terapeutické užití   aplikace a dávkování   MeSH
• tumor burden * účinky léků   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• antagonisté androgenních receptorů MeSH
• antagonisté androgenů MeSH
• apalutamide MeSH Prohlížeč
• thiohydantoiny * MeSH

Prostate cancer belongs to the most common malignant tumors in males. Almost in all patients in advanced stage, disease progression occurs despite of castration therapy. Initial treatment of metastatic disease is androgen deprivation therapy. In the case of castration-resistant disease development in asymptomatic patients, it is a combination of abiraterone acetate plus prednisone and in symptomatic patients docetaxel with prednisone are considered gold standards at the present time. The aim of therapy must be assurance of adequate quality of life, pain reduction and survival improvement. The paper presents an overview of current castration-resistant metastatic prostate cancer treatment.

• MeSH
• antagonisté androgenů terapeutické užití   MeSH
• glukokortikoidy terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci sekundární   terapie   MeSH
• orchiektomie MeSH
• progrese nemoci MeSH
• protinádorové látky terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antagonisté androgenů MeSH
• glukokortikoidy MeSH
• protinádorové látky MeSH

BACKGROUND: Cabazitaxel is an effective treatment of post-docetaxel metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the sequencing impact and identify prognostic factors of oncologic outcomes in mCRPC patients treated with cabazitaxel. METHODS: PUBMED, Web of Science, and Scopus databases were searched for articles published before January 2022 according to the PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses) statement. Studies were deemed eligible if they investigated pretreatment clinical or hematological prognostic factors of overall survival (OS) in mCRPC patients with progression after docetaxel treated with available treatments including cabazitaxel. RESULTS: Overall, 22 studies were eligible for the meta-analysis. In mCRPC patients treated with docetaxel, subsequent treatment with cabazitaxel was associated with better OS compared to that without cabazitaxel (pooled hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.56-0.89). Among the patients treated with cabazitaxel, several pretreatment clinical features and hematologic biomarkers were associated with worse OS as follows: poor performance status (PS) (pooled HR: 1.92, 95% CI: 1.33-2.77), presence of visceral metastasis (pooled HR: 2.13, 95% CI: 1.62-2.81), symptomatic disease (pooled HR: 1.47, 95% CI: 1.25-1.73), high PSA (pooled HR: 1.76, 95% CI: 1.27-2.44), high alkaline phosphatase (ALP) (pooled HR: 1.45, 95% CI: 1.28-1.65), high lactate dehydrogenase (LDH) (pooled HR: 1.54, 95% CI: 1.00-2.38), high c-reactive protein (CRP) (pooled HR: 4.40, 95% CI: 1.52-12.72), low albumin (pooled HR:1.09, 95% CI: 1.05-1.12) and low hemoglobin (pooled HR:1.55, 95% CI: 1.20-1.99). CONCLUSIONS: Sequential therapy with cabazitaxel significantly improves OS in post-docetaxel mCRPC patients. In mCRPC patients treated with cabazitaxel, patients with poor PS, visceral metastasis, and symptomatic disease were associated with worse OS. Further, pretreatment high PSA, ALP, LDH or CRP as well as low hemoglobin or albumin, were blood-based prognostic factors for OS. These findings might help guide the clinical decision-making for the use of cabazitaxel and prognostication of its OS benefit.

• Klíčová slova
• Cabazitaxel, Metastatic castration-resistant prostate cancer, Prognostic factor,
• MeSH
• docetaxel terapeutické užití   MeSH
• hemoglobiny terapeutické užití   MeSH
• lidé MeSH
• nádory prostaty rezistentní na kastraci * patologie   MeSH
• prognóza MeSH
• prostatický specifický antigen terapeutické užití   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• systematický přehled MeSH
• Názvy látek
• cabazitaxel MeSH Prohlížeč
• docetaxel MeSH
• hemoglobiny MeSH
• prostatický specifický antigen MeSH