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1.
Medicine (Baltimore) ; 100(15): e25584, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33847689

RESUMEN

INTRODUCTION: Prednisone (10 mg/d) is often used in combination with docetaxel or abiraterone in the treatment of advanced prostate cancer. LATITUDE studies have confirmed that the combination of abiraterone and prednisone (5 mg/d) can be used for the treatment of newly diagnosed high-risk metastatic castration-sensitive prostate cancer, and have achieved satisfactory results. However, it has not been reported that abiraterone combined with prednisone (5 mg/d) in the treatment of metastatic castration-resistant prostate cancer (mCRPC). PATIENT CONCERNS: Here, we present a case of high-risk advanced prostate cancer with old pulmonary tuberculosis (PTB). The patient developed a relapse of old tuberculosis in both lungs that were discovered following 14 months of continuous application of prednisone (10 mg/d). DIAGNOSIS: The histopathological findings showed prostate adenocarcinoma carcinoma with a Gleason score of 10 (5+5). Further laboratory investigations were suggestive of positive mycobacterium tuberculosis complex DNA in pleural effusion and sputum. INTERVENTIONS: The patient underwent endocrine therapy, chemotherapy of docetaxel plus prednisone, radiotherapy, and abiraterone combined with prednisone treatment, but he eventually developed into the mCRPC stage. Then, prednisone was reduced to 5 mg/d plus abiraterone, and combined with anti-tuberculosis treatment according to multi-disciplinary diagnosis and treatment. OUTCOME: Two months later, pleural effusion and atelectasis were relieved, and PSA was remained stable at a low level. The patient achieved complete remission. CONCLUSION: We cannot, with complete certainty, say that this patient, or any patient, developed old PTB recurrence due to the use of prednisone. Based on the current evidence, endocrine therapy is the foundation, radiotherapy can reduce the tumor load, and early application of abiraterone is beneficial to survival for the high-risk mCRPC. The long-term use of prednisone can be appropriately reduced in mCRPC with old PTB, and a satisfactory curative effect can be achieved. More prospective trials are warranted before a definite recommendation could be drawn.


Asunto(s)
Glucocorticoides/administración & dosificación , Mycobacterium , Prednisona/administración & dosificación , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Tuberculosis Pulmonar/tratamiento farmacológico , Anciano , Humanos , Masculino , Ilustración Médica , Neoplasias de la Próstata Resistentes a la Castración/microbiología , Recurrencia , Resultado del Tratamiento , Tuberculosis Pulmonar/complicaciones , Tuberculosis Pulmonar/microbiología
2.
Asia Pac J Clin Oncol ; 17 Suppl 3: 39-47, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33860642

RESUMEN

INTRODUCTION: Asian prostate cancer (PC) patients are particularly susceptible to docetaxel-related febrile neutropenia (FN). We evaluated primary granulocyte colony-stimulating factor (GCSF) for preventing FN in Chinese patients with metastatic hormone-sensitive PC (mHSPC) and castration-resistant PC (mCRPC). PATIENTS AND METHODS: Data from two cohorts of 377 Chinese patients with mHSPC (100; 26.5%) and mCRPC (277; 73.5%) treated with docetaxel at six public oncology centres were analysed with multivariate regression. Primary GCSF prophylaxis was defined as administration within 5 days of starting docetaxel. The primary outcome was FN within 21 days of the first docetaxel cycle (1st FN). RESULTS: Primary GCSF was given to 71 (18.8%) patients. FN occurred in 61 patients (16.2%) including 37 (9.8%) during the first cycle. Among patients who developed 1st cycle FN (n = 37) or not (n = 340), 2 and 69 received primary GCSF (5.4 vs. 20.3%, P = .03). Primary GCSF was associated with an overall reduced risk of 1st cycle FN (odds ratio [OR] = 0.22; 95% confidence interval [CI]: 0.05-0.96, P = .04), and similar trends were observed in the mHSPC (OR = 0.36, P = .35) and mCRPC (OR = 0.16, P = .08) subgroups. Poor Eastern Cooperative Oncology Group performance status (>1) was associated with an increased risk of 1st FN (OR = 3.90; 95% CI: 1.66-9.13, P = .002). CONCLUSIONS: To alleviate the risk of docetaxel-related FN, primary GCSF prophylaxis is suggested for Asian mCRPC and mHSPC patients, particularly those with poor performance status.


Asunto(s)
Docetaxel/efectos adversos , Neutropenia Febril/inducido químicamente , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/complicaciones , Adulto , Anciano , Anciano de 80 o más Años , China , Estudios de Cohortes , Humanos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Estudios Retrospectivos
7.
J Biomed Nanotechnol ; 17(1): 78-89, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33653498

RESUMEN

Currently chemotherapy drugs are usually used as first-line treatments for castration-resistant prostate cancer (CRPC), but they are ineffective and accompanied by serious side effects. MicroRNA-34a (miR-34a) simultaneously targets multiple genes related to the cell apoptosis in CRPC cells without obvious side effects. It has shown great potential in the treatment of CRPC. Previous studies focused on miR-34a increasing the sensitivity of chemotherapy drugs to chemoresistant prostate cancer cells. There are few researches on miR-34a alone in the treatment of CRPC. But the macromolecular miR-34a is difficult to enter the cell and is easily degraded by nuclease. Therefore, we constructed methoxy polyethylene glycol-polylacticco-glycolic acid-polylysine (mPEG-PLGA-PLL) nanoparticles to encapsulate miR-34a (miR-34a/NP). The results showed that miR-34a/NP protects miR-34a from degradation by nucleases and can be phagocytized by PC-3 CRPC cells. Ultrasound induces microbubble cavitation (UIMC) improves cell membrane permeability and capillary gaps, and further promotes miR-34a/NP to enter cells PC-3 and prostate cancer xenografts. The miR-34a/NP that enters the cell and tumor tissue releases miR-34a, which suppressed CRPC cells PC-3 proliferation, promoted its apoptosis, and inhibited the growth of CRPC xenografts. Our research verified that miR-34a/NP, especially combined with UIMC, has a significant anti-tumor effect on CRPC.


Asunto(s)
MicroARNs , Nanopartículas , Neoplasias de la Próstata Resistentes a la Castración , Línea Celular Tumoral , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Microburbujas , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética
8.
Nat Commun ; 12(1): 1714, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33731701

RESUMEN

Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-ß induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling.


Asunto(s)
Neoplasias Óseas/secundario , Carcinogénesis , Transición Epitelial-Mesenquimal , Factores de Transcripción de Tipo Kruppel/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Acetilación , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencilaminas/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Ciclamas/uso terapéutico , Docetaxel/uso terapéutico , Humanos , Interleucina-11/genética , Interleucina-11/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Masculino , Ratones , Mutación , Osteogénesis , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/genética , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Receptores CXCR4/antagonistas & inhibidores , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo
9.
Int J Mol Sci ; 22(4)2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33557050

RESUMEN

Prostate cancer is the most frequent malignancy in the worldwide male population; it is also one of the most common among all the leading cancer-related death causes. In the last two decades, the therapeutic scenario of metastatic castration-resistant prostate cancer has been enriched by the use of chemotherapy and androgen receptor signaling inhibitors (ARSI) and, more recently, by immunotherapy and poly(ADP-ribose) polymerase (PARP) inhibitors. At the same time, several trials have shown the survival benefits related to the administration of novel ARSIs among patients with non-castration-resistant metastatic disease along with nonmetastatic castration-resistant cancer too. Consequently, the therapeutic course of this malignancy has been radically expanded, ensuring survival benefits never seen before. Among the more recently emerging agents, the so-called "antibody-drug conjugates" (ADCs) are noteworthy because of their clinical practice changing outcomes obtained in the management of other malignancies (including breast cancer). The ADCs are novel compounds consisting of cytotoxic agents (also known as the payload) linked to specific antibodies able to recognize antigens expressed over cancer cells' surfaces. As for prostate cancer, researchers are focusing on STEAP1, TROP2, PSMA, CD46 and B7-H3 as optimal antigens which may be targeted by ADCs. In this paper, we review the pivotal trials that have currently changed the therapeutic approach to prostate cancer, both in the nonmetastatic castration-resistant and metastatic settings. Therefore, we focus on recently published and ongoing trials designed to investigate the clinical activity of ADCs against prostate malignancy, characterizing these agents. Lastly, we briefly discuss some ADCs-related issues with corresponding strategies to overwhelm them, along with future perspectives for these promising novel compounds.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Inmunoconjugados/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Animales , Antineoplásicos Inmunológicos/farmacología , Biomarcadores de Tumor , Ensayos Clínicos como Asunto , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Humanos , Inmunoconjugados/farmacología , Masculino , Terapia Molecular Dirigida , Pronóstico , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/mortalidad , Neoplasias de la Próstata/patología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/etiología , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Nivel de Atención , Resultado del Tratamiento
10.
Int J Clin Oncol ; 26(4): 753-763, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33575828

RESUMEN

BACKGROUND: Based on results from Japanese post-marketing surveillance, exploratory analyses were performed to investigate real-world outcomes of radium-223 for metastatic CRPC (mCRPC) according to patient characteristics. METHODS: This non-interventional, prospective study enrolled mCRPC patients selected for radium-223 treatment in clinical practice. Six-month safety and effectiveness were evaluated in subgroups who had/had not received prior chemotherapy (prior-chemo/no prior-chemo groups), and a subgroup who had not received concomitant androgen-receptor axis-targeted agents (ARATs). RESULTS: In the overall population (n = 296), the prior-chemo group (n = 126) tended to have more bone metastases, more analgesic use, and higher prostate-specific antigen values than the no prior-chemo group (n = 170). Incidences of treatment-emergent adverse events (TEAEs), drug-related TEAEs, and ≥ grade 3 drug-related hematological TEAEs were 47% vs. 53%, 25% vs. 29%, and 4% vs. 7% in the no prior-chemo and prior-chemo groups, respectively. Incidences of TEAEs (61%), drug-related TEAEs (36%), and ≥ grade 3 drug-related hematological events (12%) were numerically higher in 33 patients who had received two lines of prior chemotherapy. Multivariate analysis showed that two lines of prior chemotherapy, and hemoglobin, platelet, and lactate dehydrogenase values were baseline factors significantly related to ≥ grade 2 platelet count decreased. Safety and effectiveness in patients without concomitant ARATs (n = 201) were similar to those in the overall population. CONCLUSION: In a real-life setting, radium-223 was well tolerated irrespective of prior chemotherapy, but relatively higher incidences of TEAEs and hematotoxicities were suggested in patients with two lines of prior chemotherapy, possibly reflecting more advanced disease. Radium-223 safety and effectiveness in patients without concomitant ARATs were favorable.


Asunto(s)
Neoplasias Óseas , Neoplasias de la Próstata Resistentes a la Castración , Andrógenos , Neoplasias Óseas/tratamiento farmacológico , Humanos , Japón , Masculino , Vigilancia de Productos Comercializados , Estudios Prospectivos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Radioisótopos , Radio (Elemento) , Resultado del Tratamiento
11.
Future Oncol ; 17(14): 1699-1707, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33554636

RESUMEN

This is a summary of a publication about the ARAMIS (Androgen Receptor Antagonizing Agent for Metastasis-free Survival) trial, which was published in the New England Journal of Medicine in September 2020. The trial was in adult participants with nonmetastatic, castration-resistant prostate cancer (nmCRPC) who received a trial treatment called darolutamide (brand name Nubeqa®). Darolutamide is currently available as an oral treatment for adults with nmCRPC. The ARAMIS trial looked at darolutamide taken by mouth in 1509 participants from 36 countries with nmCRPC (prostate cancer that has not spread to other parts of the body and no longer responds adequately to initial hormone therapy). The trial showed that darolutamide in addition to hormone therapy increased the length of time that the trial participants were still alive for and lowered the risk of death by 31% compared with placebo (sugar pill) and hormone therapy. The participants who received darolutamide and hormone therapy also had longer time to worsening pain, needing chemotherapy, and having cancer-related bone fractures or symptoms related to cancer-related bone fractures compared with those who received placebo and hormone therapy during the trial. In general, the percentage of participants who experienced medical problems (referred to as adverse events) was similar between those who received darolutamide and those who received placebo, in addition to hormone therapy. This summary also includes insights and perspectives from a participant who was in the ARAMIS trial and from a prostate cancer patient advocate. To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Clinical Trial Registration: NCT02200614 (ClinicalTrials.gov).


Asunto(s)
Neoplasias de la Próstata Resistentes a la Castración , Antagonistas de Receptores Androgénicos , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Pirazoles
12.
Prog Urol ; 31(5): 243-244, 2021 04.
Artículo en Francés | MEDLINE | ID: mdl-33468416
13.
Cancer Invest ; 39(3): 251-256, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33393849

RESUMEN

We investigated the efficacy and safety profiles of 4-weekly docetaxel for castration-resistant prostate cancer. Patients treated with ≥2 courses of docetaxel chemotherapy (median, 70 mg/m2) between 2008 and 2018 were included. Among 125 Japanese men, 40 (32.0%) and 85 (68.0%) were treated with 3-weekly and 4-weekly regimens, respectively. In the 4-weekly regimen, the risks of progression, treatment failure, and any-cause mortality were comparable to those in the 3-weekly regimen. The incidences of severe adverse events were also similar between the 3-weekly and 4-weekly regimens. These data suggest that the 4-weekly regimen may be an acceptable option for selected patients.


Asunto(s)
Antineoplásicos/efectos adversos , Antineoplásicos/uso terapéutico , Docetaxel/efectos adversos , Docetaxel/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Anciano , Antineoplásicos/administración & dosificación , Grupo de Ascendencia Continental Asiática , Docetaxel/administración & dosificación , Humanos , Estimación de Kaplan-Meier , Masculino , Pronóstico , Neoplasias de la Próstata Resistentes a la Castración/mortalidad , Neoplasias de la Próstata Resistentes a la Castración/patología , Insuficiencia del Tratamiento , Resultado del Tratamiento
14.
Value Health ; 24(1): 121-128, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33431146

RESUMEN

OBJECTIVES: Abiraterone acetate is registered for the treatment of metastatic castration-sensitive and resistant prostate cancer (mCRPC). Treatment outcome is associated with plasma trough concentrations (Cmin) of abiraterone. Patients with a plasma Cmin below the target of 8.4 ng/mL may benefit from treatment optimization by dose increase or concomitant intake with food. This study aims to investigate the cost-effectiveness of monitoring abiraterone Cmin in patients with mCRPC. METHODS: A Markov model was built with health states progression-free survival, progressed disease, and death. The benefits of monitoring abiraterone Cmin followed by a dose increase or food intervention were modeled via a difference in the percentage of patients achieving adequate Cmin taking a healthcare payer perspective. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainties and their impac to the incremental cost-effectiveness ratio (ICER). RESULTS: Monitoring abiraterone followed by a dose increase resulted in 0.149 incremental quality-adjusted life-years (QALYs) with €22 145 incremental costs and an ICER of €177 821/QALY. The food intervention assumed equal effects and estimated incremental costs of €7599, resulting in an ICER of €61 019/QALY. The likelihoods of therapeutic drug monitoring (TDM) with a dose increase or food intervention being cost-effective were 8.04%and 81.9%, respectively. CONCLUSIONS: Monitoring abiraterone followed by a dose increase is not cost-effective in patients with mCRPC from a healthcare payer perspective. Monitoring in combination with a food intervention is likely to be cost-effective. This cost-effectiveness assessment may assist decision making in future integration of abiraterone TDM followed by a food intervention into standard abiraterone acetate treatment practices of mCRPC patients.


Asunto(s)
Acetato de Abiraterona/uso terapéutico , Antineoplásicos/uso terapéutico , Monitoreo de Drogas/economía , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Acetato de Abiraterona/sangre , Acetato de Abiraterona/economía , Anciano , Antineoplásicos/sangre , Antineoplásicos/economía , Análisis Costo-Beneficio , Supervivencia sin Enfermedad , Humanos , Masculino , Cadenas de Markov , Antígeno Prostático Específico/sangre , Años de Vida Ajustados por Calidad de Vida
15.
J Med Chem ; 64(2): 909-924, 2021 01 28.
Artículo en Inglés | MEDLINE | ID: mdl-33470111

RESUMEN

Persistent androgen receptor (AR) activation drives therapeutic resistance to second-generation AR pathway inhibitors and contributes to the progression of advanced prostate cancer. One resistance mechanism is point mutations in the ligand binding domain of AR that can transform antagonists into agonists. The AR F877L mutation, identified in patients treated with enzalutamide or apalutamide, confers resistance to both enzalutamide and apalutamide. Compound 4 (JNJ-pan-AR) was identified as a pan-AR antagonist with potent activity against wild-type and clinically relevant AR mutations including F877L. Metabolite identification studies revealed a latent bioactivation pathway associated with 4. Subsequent lead optimization of 4 led to amelioration of this pathway and nomination of 5 (JNJ-63576253) as a clinical stage, next-generation AR antagonist for the treatment of castration-resistant prostate cancer (CRPC).


Asunto(s)
Antagonistas de Receptores Androgénicos/farmacología , Nitrilos/farmacología , Picolinas/farmacología , Piperidinas/farmacología , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata/tratamiento farmacológico , Piridinas/farmacología , Compuestos de Espiro/farmacología , Antagonistas de Receptores Androgénicos/farmacocinética , Antagonistas de Receptores Androgénicos/uso terapéutico , Animales , Biotransformación , Línea Celular Tumoral , Perros , Descubrimiento de Drogas , Resistencia a Antineoplásicos/genética , Hepatocitos/metabolismo , Humanos , Masculino , Modelos Moleculares , Mutación , Nitrilos/farmacocinética , Nitrilos/uso terapéutico , Picolinas/farmacocinética , Picolinas/uso terapéutico , Piperidinas/farmacocinética , Piperidinas/uso terapéutico , Neoplasias de la Próstata/genética , Neoplasias de la Próstata Resistentes a la Castración/genética , Piridinas/farmacocinética , Piridinas/uso terapéutico , Ratas , Compuestos de Espiro/farmacocinética , Compuestos de Espiro/uso terapéutico , Relación Estructura-Actividad
16.
Cancer Treat Rev ; 93: 102152, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33486302

RESUMEN

PURPOSE: To evaluate the impact of the hormonal treatment sequencing including abiraterone acetate plus prednisone (AAP) and enzalutamide (ENZ) in mCRPC, and determine which sequence provides more benefits for patients. METHODS: Studies published in English between 1 January 2013 and 30 September 2017 were identified in PubMed and EMBASE electronic databases. Studies assessing the efficacy of treatment sequences, based on AAP and ENZ, in mCRPC patients, were eligible for analysis. RESULTS: Seventeen studies met the inclusion criteria. Two assessed both treatment sequences AAP â†’ ENZ and ENZ â†’ AAP; it was found that sequence of AAP â†’ ENZ showed a statistically significantly longer PSA-PFS than the observed in ENZ â†’ AAP (pooled HR: 0,54; 95% CI; 0,36-0,82; p < 0,05). The nine studies analysing Doc â†’ AAP â†’ ENZ sequence, revealed favourable results in terms of PFS. The 5 studies which analysed AAP â†’ ENZ sequence, show a decrease in PSA levels ≥ 50% in 11-41% of patients treated with enzalutamide after previous treatment with AAP. In the two studies that analysed the Doc â†’ ENZ â†’ AAP sequence, PSA response rates were much lower than those reported with Doc â†’ AAP â†’ ENZ, with decreases in PSA ≥ 30 of 3-18% and PSA ≥ 50 of 8-11%. CONCLUSION: Significant clinical efficacy of AAP administered as the first-line treatment in mCRPC patients followed by enzalutamide, delaying disease progression, compared with the ENZ â†’ AAP sequence. However, more studies and randomized trials are needed, to validate the best treatment sequencing.


Asunto(s)
Acetato de Abiraterona/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Feniltiohidantoína/análogos & derivados , Prednisona/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Humanos , Masculino , Feniltiohidantoína/uso terapéutico , Resultado del Tratamiento
17.
Jpn J Clin Oncol ; 51(4): 544-551, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33324967

RESUMEN

AIM: The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. METHODS: Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon's minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. RESULTS: For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55-86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4-84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%-69.3%), median prostate-specific antigen-progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). CONCLUSIONS: Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen-progression-free survival was shorter than that reported in previous studies. Considering the benefit-risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.


Asunto(s)
Acetato de Abiraterona/efectos adversos , Acetato de Abiraterona/uso terapéutico , Andrógenos/deficiencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Prednisolona/uso terapéutico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/patología , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Prednisolona/administración & dosificación , Supervivencia sin Progresión , Resultado del Tratamiento
18.
Int Braz J Urol ; 47(2): 359-373, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33284538

RESUMEN

BACKGROUND: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. OBJECTIVE: To present survey results on management of M0 CRPC in Brazil. DESIGN, SETTING, AND PARTICIPANTS: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. CONCLUSIONS: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.


Asunto(s)
Consenso , Médicos , Neoplasias de la Próstata Resistentes a la Castración , Brasil , Humanos , Masculino , Selección de Paciente , Percepción , Neoplasias de la Próstata Resistentes a la Castración/diagnóstico , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Resultado del Tratamiento
20.
Urologe A ; 60(2): 212-221, 2021 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-33346857

RESUMEN

The treatment of advanced prostate cancer is changing. New study data and the resulting new therapeutic options have led to increasingly differentiated treatment decisions. Despite the changing therapy landscape, taxane-based chemotherapy-being a life-prolonging treatment-remains an indispensable therapeutic component for chemotherapy-fit patients in the metastatic setting. The current results of the randomized study CARD show that cabazitaxel has a higher oncological effectiveness, including a significant survival benefit and no negative impact on quality of life parameters, compared to a second androgen receptor targeted agent (ARTA) in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed after treatment with docetaxel and an androgen receptor-targeted agent (ARTA). In mCNPC the combination therapies of ADT (androgen deprivation therapy) plus docetaxel or of ADT plus ARTA have been established. In addition, three ARTAs tested in recent phase III studies in a clinical setting for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) showed that their use significantly prolongs metastasis-free survival and overall survival. The potential early use of ARTAs also has implications for the treatment of mCNPC. The aim of this publication is to provide guidance for clinical routine and to develop criteria for individual therapy decisions with a special focus on the use of chemotherapy.


Asunto(s)
Antagonistas de Andrógenos , Neoplasias de la Próstata Resistentes a la Castración , Antagonistas de Andrógenos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Docetaxel/uso terapéutico , Humanos , Masculino , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Calidad de Vida , Receptores Androgénicos , Resultado del Tratamiento
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