Metastazující kastračně rezistentní karcinom prostaty (metastatic castration resistant prostate cancer, mCRPC) představuje nejzávažnější formu široké skupiny karcinomů prostaty. Je typický rezistencí k primární androgen deprivační terapii, proto je pro účinnou léčbu nutné rozšířit léčebné spektrum. Čím více linií terapie použijeme, tím lze život pacientů s mCRPC více prodloužit. Jednou z léčebných možností je i cílená léčba. Inhibitory poly(ADP-ribóza) polymerázy (PARP) prokázaly u těchto pacientů účinnost jednak v monoterapii, jednak v kombinaci s léčbou cílenou na androgenní receptor. Článek se věnuje postavení inhibitoru PARP talazoparibu v léčbě mCRPC.

Metastatic castration resistant prostate cancer (mCRPC) represents the most severe form of a group of prostate cancer. It is characterized by resistance to primary androgen deprivation therapy, which necessitates the expansion of the treatment spectrum for effective management. The more lines of therapy we use, the more we can prolong the survival of patients with mCRPC. One of the treatment options is targeted therapy. Poly(ADP-ribose) polymerase (PARP) inhibitors have demonstrated efficacy, both in monotherapy and in combination with androgen receptor targeted therapy in these patients. The article discusses the role of the PARP inhibitor talazoparib in the treatment of mCRPC.

Kastračně rezistentní karcinom prostaty bez průkazu metastazujícího onemocnění podle standardních zobrazovacích metod (CT a scintigrafie skeletu) či vyšetření nové generace (PET/CT) klasifikujeme jako nemetastazující CRPC (non-metastatic castration-resistant prostate cancer, nmCRPC). Ještě před několika lety nebyla k dispozici žádná účinná léčba tohoto onemocnění. Pacienti postupně progredovali do metastazujícího onemocnění, které je spojeno s rozvojem vzniku celého spektra komplikací a sníženou kvalitou života. Cílem léčby nmCRPC je proto prodloužení doby do vzniku metastatického stadia a prodloužení i celkového přežití. Toto potvrdily tři významné prospektivní klinické studie fáze III. Studie hodnotily antiandrogeny druhé generace, kam řadíme apalutamid, enzalutamid a darolutamid.

Castration-resistant prostate cancer with absence of metastatic disease according to standard imaging methods (CT and skeletal scintigraphy) or newer PET/CT is classified as non-metastatic CRPC (nmCRPC). Until a few years ago, no effective treatment was available for this disease. Patients gradually progressed to metastatic disease, which is associated with the development of a whole spectrum of complications and with a worse quality of life. The aim of nmCRPC treatment is therefore to prolong the time to the development of the metastatic disease and to prolong overall survival. This has been confirmed by three major prospective phase III clinical trials. The studies evaluated second generation antiandrogens, which include apalutamide, enzalutamide and darolutamide.

• MeSH
• lidé MeSH
• nádory prostaty * diagnóza   epidemiologie   terapie   MeSH
• prostatický specifický antigen analýza   MeSH
• protokoly protinádorové léčby MeSH
• radioterapie MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• přehledy MeSH

AIMS: The objective of this study was to investigate the association and combined prognostic significance of the PD-L1, Smoothened protein and β-catenin expressions in patients with clear cell renal cell carcinoma (ccRCC). METHODS: The PD-L1, Smoothened protein and β-catenin expression were evaluated in 104 ccRCC patients. All studied tumor samples were acquired from nephrectomy specimens of primary tumors and not from biopsies or metastases. An indirect immunohistochemistry using polyclonal rabbit anti-Smoothened antibody, monoclonal mouse anti-human β-catenin-1 antibody, immunohistochemical assay PD-L1 28-8 pharmDx using monoclonal rabbit anti-PD-L1 antibody and anti-VHL (C- terminal) rabbit antibody was used. Immunohistochemistry was scored semiquantitavely. RESULTS: Median overall survival (OS) was significantly better in patients with lower PD-L1 expression (≤5%), Smoothened protein (SMO) expression (<5%) or cytoplasmic β-catenin expression (≤75%) than in patients with higher expressions of these biomarkers (P<0.001, P=0.047, and P<0.001, respectively). Membranous β-catenin showed an opposite effect with its lower expression (≤75%) being associated with longer OS (P=0.020). There was significant association between PD-1 and PD-L1 expression (P=0.007) and significant association of tumor grade (WHO 2016) with membranous β-catenin (P<0.001), cytoplasmic β-catenin (P=0.005), pVHL (P=0.042), PD-L1 (P=0.049) and PD-1 (P=0.028) expression. CONCLUSION: The present study provides the first data on the potential association and combined prognostic significance of frequency of primary cilia, PD-L1, Smoothened protein and β-catenin expression with the outcome in clear cell renal cell carcinoma.

• MeSH
• antigeny CD274 * metabolismus   MeSH
• beta-katenin * metabolismus   MeSH
• cilie * metabolismus   patologie   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• karcinom z renálních buněk * metabolismus   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory ledvin * metabolismus   mortalita   patologie   MeSH
• prognóza MeSH
• receptor Smoothened metabolismus   MeSH
• receptory spřažené s G-proteiny * metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• komentáře MeSH

Léčba pokročilého karcinomu prostaty v posledních letech dosáhla výrazného pokroku. V případě hormonálně senzitivního onemocnění se nejedná již jen o samotnou androgen deprivační léčbu, ale její kombinaci s léčbou cílenou na androgenní receptor (androgen receptor target agents, ARTA) či chemoterapii. Poslední data ukazují, že lze postupy vzájemně zkombinovat i do tripletu. V případě metastazujícího kastračně rezistentního karcinomu prostaty se kromě chemoterapie či ARTA uplatňují i další postupy jako podání radionuklidů a cílené terapie. Zatím ve srovnání s jinými solidními nádory se méně využívají možnosti imunoterapie.

The treatment of advanced prostate cancer has made significant changes in recent years. In the case of hormone-sensitive prostate cancer, it is no longer just androgen deprivation therapy, but its combination with androgen receptor target agents (ARTA) or chemotherapy. The late data show that it is possible to combine the procedures into a triplet. In the case of metastatic castration-resistant prostate cancer, in addition to chemotherapy or ARTA, other treatment is also used, such as radionuclides, targeted therapy. In the compared to other solid tumors, immunotherapy have been used less.

AIMS: Abiraterone treatment requires regular drug intake under fasting conditions due to pronounced food effect, which may impact patient adherence. The aim of this prospective study was to evaluate adherence to abiraterone treatment in patients with prostate cancer. To achieve this aim, an abiraterone population pharmacokinetic model was developed and patients' adherence has been estimated by comparison of measured levels of abiraterone with population model-based simulations. METHODS: A total of 1469 abiraterone plasma levels from 83 healthy volunteers collected in a bioequivalence study were analysed using a nonlinear mixed-effects model. Monte Carlo simulation was used to describe the theoretical distribution of abiraterone pharmacokinetic profiles at a dose of 1000 mg once daily. Adherence of 36 prostate cancer patients treated with abiraterone was then evaluated by comparing the real abiraterone concentration measured in each patient during follow-up visit with the theoretical distribution of profiles based on simulations. Patients whose abiraterone levels were ˂5th or ˃95th percentile of the distribution of simulated profiles were considered to be non-adherent. RESULTS: Based on this evaluation, 13 patients (36%) have been classified as non-adherent. We observed significant association (P = .0361) between richness of the breakfast and rate of non-adherence. Adherent patients reported significantly better overall condition in self-assessments (P = .0384). A trend towards a higher occurrence of adverse effects in non-adherent patients was observed. CONCLUSIONS: We developed an abiraterone population pharmacokinetic model and proposed an advanced approach to medical adherence evaluation. Due to the need for administration under fasting conditions, abiraterone therapy is associated with a relatively high rate of non-adherence.

• MeSH
• adherence k farmakoterapii * statistika a číselné údaje   MeSH
• androsteny * farmakokinetika   aplikace a dávkování   terapeutické užití   MeSH
• biologické modely * MeSH
• dospělí MeSH
• interakce mezi potravou a léky MeSH
• lidé středního věku MeSH
• lidé MeSH
• metoda Monte Carlo MeSH
• nádory prostaty * farmakoterapie   MeSH
• omezení příjmu potravy MeSH
• prospektivní studie MeSH
• protinádorové látky farmakokinetika   aplikace a dávkování   MeSH
• senioři MeSH
• terapeutická ekvivalence MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH

Kazuistika poukazuje na možnost farmakologické terapie everolimem u pacientů s chirurgicky neřešitelným rozsáhlým postižením ledvin angiomyolipomy, které pacienty ohrožují závažným krvácením.

The case study highlights the possibility of pharmacological therapy with everolimus for patients with extensive kidney angiomyolipomatosis, which poses a serious risk of bleeding to the patients.

• MeSH
• angiomyolipom * farmakoterapie   komplikace   MeSH
• diagnostické zobrazování metody   MeSH
• dospělí MeSH
• everolimus * škodlivé účinky   terapeutické užití   MeSH
• krvácení etiologie   MeSH
• lidé MeSH
• nádory ledvin * diagnóza   terapie   MeSH
• stomatitida etiologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

The objective of this study was to investigate the prognostic significance of the frequency of primary cilia (PC) and β-catenin expression in 218 patients (pts) with non-small cell lung cancer (NSCLC), including 125 pts with adenocarcinoma and 93 pts with squamous cell carcinoma. In the whole group of 218 pts with NSCLC, overall survival (OS) was significantly inferior among pts with present PC than without PC (p=0.024) and with higher cytoplasmic β-catenin expression (25-75%) than with lower cytoplasmic β-catenin expression (<25%) (p=0.008). In the univariate Cox proportional hazard model, the hazard ratio was 1.653 in pts with present PC (p=0.026) and 1.851 in pts with higher cytoplasmic β-catenin (25-75%) (p=0.009). Multivariate testing of the whole group of 218 pts with NSCLC showed that the presence of PC was associated with a worse prognosis (p=0.018). In the subgroup of 125 pts with adenocarcinoma, OS was significantly improved in pts with higher membranous β-catenin expression (≥50%) than in pts with lower expression (<50%) (p=0.0300) and OS was significantly inferior in pts with higher cytoplasmic β-catenin expression (25-75%) than in pts with lower expression (<25%) (p=0.0004). Multivariate testing of the subgroup of pts with adenocarcinoma showed that cytoplasmic β-catenin (p<0.001) and pleural invasion (p=0.017) were associated with worse prognosis. The present results indicate a negative prognostic significance of PC and cytoplasmic β-catenin expression in NSCLC and a negative prognostic significance of cytoplasmic β-catenin expression in adenocarcinoma.

• MeSH
• adenokarcinom patologie   metabolismus   mortalita   MeSH
• beta-katenin * metabolismus   MeSH
• cilie * patologie   metabolismus   MeSH
• cytoplazma * metabolismus   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery metabolismus   MeSH
• nádory plic * patologie   metabolismus   mortalita   MeSH
• nemalobuněčný karcinom plic * patologie   metabolismus   mortalita   MeSH
• prognóza MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom patologie   metabolismus   mortalita   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The aim was to assess therapeutic outcomes and tolerance in patients with metastatic castration resistant prostate cancer (mCRPC) treated with androgen receptor targeted agents (ARTA) treatment at one oncological center in the Czech Republic. MATERIALS AND METHODS: Retrospective analysis of 64 patients with mCRPC treated with abiraterone (50 patients) and enzalutamide (14 patients) in the first line of this disease was conducted. Kaplan-Meier analysis was used to calculate progression free survival (PFS) and overall survival (OS). We performed a multivariate analysis of risk factors for treatment outcomes (PFS, OS) by Cox regression analysis. RESULTS: The median follow-up was 28.4 months. The median PFS was 15.4 months [95% confidence interval (CI): 12.3-18.5], median OS was 38.2 months (95% CI: 19.9-56.5). Regression analysis demonstrated a favorable prognostic effect on PFS in patients with reduction of PSA ≥ 50 %, in patients with early reduction of prostate-specific antigen (PSA) ≥ 50% within 3 months, in patients younger than 74 years and in overall performance status (PS) 0. Regression analysis demonstrated a favorable prognostic effect on OS in patients with reduction of PSA ≥ 50 %, in patients with early reduction of PSA ≥ 50 % within 3 months and in patients with overall PS 0. Adverse effects grade 3-4 were reported in 17 (27.9%) patients in abirateron arm and in 1 (7.1%) patient in enzalutamide arm. CONCLUSION: The analysis of patients with mCRPC treated with ARTA in the first line showed that ARTA represents an effective and safe therapy and contributes to longer survival.

• Publikační typ
• časopisecké články MeSH