Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.124
Filtrar
1.
J Clin Neurosci ; 88: 226-231, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33992189

RESUMO

INTRODUCTION: Previous studies have suggested a significant increase in plasma homocysteine (Hcy) levels in levodopa-treated Parkinson's disease (PD) patients, and vitamin B12 and folate supplementation may decrease Hcy levels. However, the effects of catechol-O-methyltransferase inhibitors on levodopa-induced increase in Hcy levels were conflicting. The aim of this study was to evaluate whether Hcy levels are increased in levodopa-treated PD patients and to evaluate the effects of vitamin B12 and folate or entacapone on Hcy levels in levodopa-treated PD patients. METHODS: We analyzed and compared plasma Hcy levels in 20 levodopa-naïve PD patients and 42 levodopa-treated PD patients, followed by randomized assignment of 42 levodopa-treated patients to treatment groups with either vitamin B12 and folate, entacapone, or no medication. RESULTS: Plasma Hcy levels in levodopa-treated PD patients were higher than those in the control group, but the difference was not statistical significant (15.25 ± 6.70 and 13.13 ± 4.68, P = 0.216). Patients treated with vitamin B12 and folate had a significant decrease in plasma Hcy levels (P < 0.001). In the entacapone group, Hcy levels were mildly decreased, but the change did not reach statistical significance. CONCLUSION: Levodopa-treated PD patients had higher plasma Hcy than levodopa-naive PD patients. Unlike entacapone, combination supplementation with vitamin B12 and folate was associated with significantly decreased plasma Hcy. We suggest that plasma Hcy levels should be monitored during levodopa treatment, and supplementation with inexpensive vitamin B12 and folate is beneficial for levodopa-treated patients.


Assuntos
Antiparkinsonianos/uso terapêutico , Catecóis/uso terapêutico , Homocisteína/sangue , Nitrilas/uso terapêutico , Doença de Parkinson/sangue , Doença de Parkinson/tratamento farmacológico , Idoso , Feminino , Ácido Fólico/uso terapêutico , Homocisteína/efeitos dos fármacos , Humanos , Hiper-Homocisteinemia/induzido quimicamente , Hiper-Homocisteinemia/prevenção & controle , Levodopa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Projetos de Pesquisa , Vitamina B 12/uso terapêutico
2.
Breast Cancer Res Treat ; 188(2): 433-439, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33860388

RESUMO

INTRODUCTION: Neoadjuvant endocrine therapy is often utilized to downstage Estrogen Receptor-positive (ER+) breast cancer prior to surgery. However, this approach is sometimes met with endocrine resistance mechanisms within the tumor. This trial examines the safety and efficacy of tamoxifen in combination with an mTORC1/2 inhibitor, TAK-228, in the neoadjuvant treatment of ER+ breast cancer. METHODS: In this single-arm, open-label trial, pre- and post-menopausal women were enrolled to receive neoadjuvant tamoxifen (20 mg daily) with TAK-228 (30 mg weekly) for 16 weeks prior to surgery. Patient had tissue sampling at baseline, week 6, and week 16. The primary endpoint was change in Ki-67 from baseline to 6 weeks. The toxicity, change in tumor size, pathologic complete response rate, PEPI score, and baseline Oncotype Dx score were also assessed. RESULTS: Twenty-eight women were enrolled on the trial, and 25 completed the entire study course. The combination of tamoxifen and TAK-228 resulted in a significant reduction in Ki-67 from 18.3 to 15.2% (p = 0.0023). The drug was also found to be safe and tolerable. While nausea and hyperglycemia were common side effects, these were manageable. The tumor size also significantly decreased with the treatment, with a median decrease of 0.75 cm (p < 0.0001). There were no pathologic complete responses. CONCLUSION: Tamoxifen and TAK-228 was safe and well tolerated neoadjuvant treatment for ER+ breast cancer, preliminary evidence of activity with significant reduction in both Ki-67 and tumor size, warranting further evaluation in a larger study.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzoxazóis , Neoplasias da Mama/tratamento farmacológico , Feminino , Hormônios/uso terapêutico , Humanos , Nitrilas/uso terapêutico , Pirimidinas , Receptor ErbB-2/genética , Receptores de Estrogênio , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Triazóis/uso terapêutico
3.
Int J Hematol ; 114(1): 65-78, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33851349

RESUMO

Bosutinib is approved in the United States, Europe, Japan, and other countries for treatment of newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML), and CML resistant/intolerant to prior therapy. In the phase 3 BFORE trial (Clinicaltrials.gov, NCT02130557), patients were randomized 1:1 to first-line bosutinib or imatinib 400 mg once daily. We examined efficacy, safety, and patient-reported outcomes of bosutinib vs imatinib and pharmacokinetics of bosutinib in the Asian (n = 33 vs 34) and non-Asian (n = 235 vs 234) subpopulations of BFORE followed for at least 24 months. At the data cutoff date, 72.7 vs 66.7% of Asian and 70.6 vs 66.4% of non-Asian patients remained on treatment. The major molecular response rate at 24 months favored bosutinib vs imatinib among Asian (63.6 vs 38.2%) and non-Asian (60.9 vs 52.6%) patients, as did the complete cytogenetic response rate by 24 months (86.7 vs 76.7%, 81.5 vs 76.3%). Treatment-emergent adverse events in both subpopulations were consistent with the primary BFORE results. Trough bosutinib concentration levels tended to be higher in Asian patients. Health-related quality of life was maintained after 12 months of bosutinib in both subpopulations. These results support bosutinib as a first-line treatment option in Asian patients with CP CML.


Assuntos
Compostos de Anilina/uso terapêutico , Antineoplásicos/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Nitrilas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/efeitos adversos , Compostos de Anilina/sangue , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Ásia/epidemiologia , Feminino , Humanos , Mesilato de Imatinib/efeitos adversos , Mesilato de Imatinib/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/epidemiologia , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/sangue , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/sangue , Quinolinas/efeitos adversos , Quinolinas/sangue , Resultado do Tratamento , Adulto Jovem
4.
J Med Case Rep ; 15(1): 207, 2021 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33910628

RESUMO

BACKGROUND: Adjuvant endocrine therapy is recommended for the treatment of hormone-receptor-positive breast cancer. Aromatase inhibitors are associated with significant musculoskeletal adverse effects, likely through growth hormone/insulin-like growth factor 1 modulation, while tamoxifen reduces insulin-like growth factor 1 production. We describe the case of a patient who was treated successfully with tamoxifen for her hormone-receptor-positive breast cancer and acromegaly. CASE PRESENTATION: A 57-year old White female with hormone-receptor-positive breast cancer was diagnosed with acromegaly. She received adjuvant endocrine therapy with anastrozole but could not tolerate this medication because of severe arthralgia, so she was switched to tamoxifen. Shortly after starting tamoxifen, the patient's musculoskeletal symptoms resolved and her insulin-like growth factor 1 levels normalized. She has remained in remission of her acromegaly and breast cancer since initiating tamoxifen. CONCLUSION: This case highlights the dual benefit of tamoxifen therapy in the treatment of hormone-receptor-positive breast cancer and acromegaly. Unlike anastrozole, tamoxifen has the benefit of lowering insulin-like growth factor 1 levels, which underscores its advantage in reducing adverse musculoskeletal symptoms during the treatment of hormone-receptor-positive breast cancer. We offer the first reported use of tamoxifen monotherapy for the successful treatment of acromegaly and hormone-receptor-positive breast cancer. While tamoxifen may offer an additional, oral option for acromegaly patients who do not respond to or tolerate conventional growth-hormone-lowering therapy, additional studies are necessary.


Assuntos
Acromegalia , Neoplasias da Mama , Acromegalia/tratamento farmacológico , Anastrozol/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Nitrilas/uso terapêutico , Tamoxifeno/uso terapêutico
6.
Int J Hematol ; 113(5): 624-631, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33782818

RESUMO

The advent of tyrosine kinase inhibitors (TKIs) has dramatically improved the outcome of patients with chronic myeloid leukemia (CML). Currently, four TKIs are available for the frontline treatment, including the first-generation TKI (imatinib) and the second-generation TKIs (dasatinib, nilotinib, and bosutinib). The second-generation TKIs lead to a faster and deeper molecular response without a survival benefit compared with imatinib. However, the opportunity for the treatment discontinuation and functional cure requires the achievement of durable deep molecular remission. Therefore, the second-generation TKIs should be considered as initial therapy for chronic-phase CML. Switch of therapy is warranted in case of treatment failure, including resistance and/or intolerance. The life expectancy of patients with CML is approaching that of the general population. Given an expected lifespan, future perspectives should consider the strategy for the optimal choice of TKIs, allowing for long-duration of effective TKI therapy with less toxicity to aim for a functional cure. A novel prediction approach such as artificial intelligence-driven analysis on the accumulated data from clinical trials paves a promising path for the personalized recommendation on frontline TKIs and precise survival prediction.


Assuntos
Antineoplásicos/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Inibidores de Proteínas Quinases/uso terapêutico , Transplante de Células-Tronco , Compostos de Anilina/uso terapêutico , Animais , Inteligência Artificial , Dasatinibe/uso terapêutico , Gerenciamento Clínico , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Nitrilas/uso terapêutico , Pirimidinas/uso terapêutico , Quinolinas/uso terapêutico , Transplante de Células-Tronco/métodos , Transplante Homólogo/métodos
7.
Breast Cancer Res Treat ; 187(3): 769-775, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33710439

RESUMO

PURPOSE: To analyze whether monitoring serum estradiol (E2) levels using a highly sensitive and specific liquid chromatography tandem mass spectrometry (LC-MS/MS) method may identify patients with AI failure with E2 levels below the lower limit of quantification (LLOQ) after schwitching from tamoxifen to letrozole. METHODS: In a prospective study of breast cancer patients switching to letrozole treatment after previous tamoxifen, plasma estrogen levels were measured at baseline and after 3- and 12-months using LC-MS/MS. RESULTS: Forty-six patients were classified postmenopausal and entered into the final analysis. Thirty-nine (85%) patients had three- and 12-month E2 concentrations below the LLOQ (5 pmol/L). In the seven patients classified as AI-failures during letrozole treatment, serum E2-MS level rose above 5 pmol/L at 3 months with a mean E2-MS 77.5 pmol/L or 12 months with a mean E2-MS 21 pmol/L. None of the baseline variables i.e., age at diagnosis, age at study entry, age at menarche, BMI, endometrial thickness, total ovarian volume, baseline FSH, E2-IA, or E2-MS were significantly associated with the risk of AI failure in logistic regression. E2 levels at baseline measured by E2-IA did not significantly correlate to the levels measured by E2-MS. CONCLUSIONS: There is a relatively high risk of inadequate estrogen suppression in patients who switch from tamoxifen treatment to AIs. The use of sensitive and specific assays, such as LC-MS/MS methods, to monitor estrogen levels during AI treatment is essential to minimize the risk of a proceeding inefficient endocrine therapy.


Assuntos
Neoplasias da Mama , Tamoxifeno , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Cromatografia Líquida , Estradiol/uso terapêutico , Feminino , Humanos , Letrozol/uso terapêutico , Nitrilas/uso terapêutico , Estudos Prospectivos , Tamoxifeno/uso terapêutico , Espectrometria de Massas em Tandem
9.
Bull Cancer ; 108(4): 359-368, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33743960

RESUMO

BACKGROUND: Overexpression of certain long non-coding RNAs (lncRNAs) promotes the progression of castration-resistant prostate cancer (CRPC). The significance and potential role of the lncRNA designated pituitary tumour-transforming 3, pseudogene (PTTG3P) in CRPC is unknown. METHODS: We detected PTTG3P expression by qPCR. Upregulated PTTG3P expression was performed to explore the role of PTTG3P in PCa cells resistant to ADT (androgen deprivation therapy). The relationship among PTTG3P, mir-146a-3p and PTTG1 were validated by qPCR, western blot and luciferase assay. RESULTS: PTTG3P levels were significantly increased in the androgen-independent PC cell lines, as well as in CRPC tissues compared with those of the androgen-dependent prostate cancer cell line LNCaP and tumour tissues of patients with hormone-naive prostate cancers. Enforced expression of PTTG3P in androgen-deprived LNCaP cells significantly enhanced survival, clonogenicity, and tumorigenicity. Further, PTTG3P acted as a competing endogenous RNA (ceRNA, natural miRNA sponge) to upregulate PTTG1 expression by competing for mir-146a-3p in the progression to CRPC. CONCLUSION: Our findings suggest that PTTG3P promotes the resistance of prostate cancer cells to androgen-deprivation therapy via upregulating PTTG1. PTTG3P may therefore represent a potential target for therapy of CRPC.


Assuntos
Adenocarcinoma/patologia , Neoplasias de Próstata Resistentes à Castração/patologia , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Securina/biossíntese , Securina/genética , Adenocarcinoma/genética , Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Animais , Antineoplásicos Hormonais/uso terapêutico , Ligação Competitiva , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Xenoenxertos , Humanos , Masculino , Camundongos Nus , MicroRNAs/genética , MicroRNAs/metabolismo , Transplante de Neoplasias , Nitrilas/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/genética , Pseudogenes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Compostos de Tosil/uso terapêutico , Ensaio Tumoral de Célula-Tronco , Regulação para Cima
10.
Neurología (Barc., Ed. impr.) ; 36(2): 95-100, mar. 2021. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-ET6-2393

RESUMO

INTRODUCCIÓN: La esclerosis múltiple (EM) es una enfermedad crónica del sistema nervioso central que se caracteriza por la existencia de inflamación, desmielinización, gliosis y daño axonal. La introducción de dimetilfumarato y teriflunomida ha supuesto un aumento de las alternativas terapéuticas en la primera línea de tratamiento de la EM. El objetivo de este estudio fue evaluar el impacto económico de la incorporación de estas nuevas terapias orales en la Unidad de Referencia (CSUR) del Hospital Universitario Puerta de Hierro Majadahonda. MATERIAL Y MÉTODOS: Se realizó un estudio observacional retrospectivo en la población de pacientes diagnosticados de EM, en tratamiento con fármacos modificadores de la enfermedad durante el año 2015, y su seguimiento se prolongó hasta obtener un seguimiento medio superior a un año de tratamiento. Los datos se recogieron de la historia clínica electrónica y del programa de dispensación de medicamentos a pacientes externos y ambulantes del Servicio de Farmacia. RESULTADOS: Evaluando el coste del cambio del tratamiento en 125 pacientes desde otros fármacos a dimetilfumarato o teriflunomida y comparando con el coste que habría supuesto el mantenimiento de los tratamientos previos, el ahorro total durante el periodo de observación fue de 169.107,31 (Euro). CONCLUSIONES: Dimetilfumarato y teriflunomida, además de aportar nuevas alternativas terapéuticas, no solo no han supuesto un incremento sino, por el contrario, una disminución en los costes del tratamiento de la EM en nuestro hospital


INTRODUCTION: Multiple sclerosis (MS) is a chronic disease affecting the central nervous system and is characterised by inflammation, demyelination, gliosis, and axonal damage. The introduction of dimethyl fumarate and teriflunomide has led to an increase in the number of alternative first-line therapies for MS. The objective of this study was to evaluate the economic impact of the incorporation of new oral therapies at the reference unit (CSUR) at Hospital Universitario Puerta de Hierro Majadahonda. MATERIALS AND METHODS: We performed a retrospective observational study including patients diagnosed with MS, who underwent treatment with disease-modifying drugs in 2015 and were followed up for a minimum mean time of one year. Data were collected from patients' electronic clinical histories and the pharmacy service's programme for dispensing drugs to outpatients. RESULTS: Evaluating the cost of changing 125 patients' treatment from other drugs to dimethyl fumarate and teriflunomide, and comparing this with the cost that would have resulted from maintaining their previous treatment, demonstrated a total saving of (Euro)169,107.31 over the study period. CONCLUSIONS: In addition to contributing new therapeutic alternatives, dimethyl fumarate and teriflunomide produced an economic saving in MS treatment at our hospital


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Esclerose Múltipla/economia , Fumarato de Dimetilo/economia , Imunossupressores/economia , Crotonatos/economia , Hidroxibutiratos/economia , Nitrilas/economia , Toluidinas/economia , Estudos Retrospectivos , Esclerose Múltipla/tratamento farmacológico , Fumarato de Dimetilo/uso terapêutico , Imunossupressores/uso terapêutico , Crotonatos/uso terapêutico , Hidroxibutiratos/uso terapêutico , Nitrilas/uso terapêutico , Toluidinas/uso terapêutico , Adesão à Medicação
11.
Jpn J Clin Oncol ; 51(7): 1142-1148, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33621330

RESUMO

OBJECTIVE: This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). METHODS: The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. RESULTS: In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40-0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. CONCLUSIONS: This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.


Assuntos
Androstenos/uso terapêutico , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Docetaxel/uso terapêutico , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Idoso , Humanos , Masculino , Prognóstico , Neoplasias de Próstata Resistentes à Castração/mortalidade , Análise de Sobrevida
12.
J Urol ; 205(6): 1648-1654, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33577365

RESUMO

PURPOSE: Long-term androgen deprivation therapy has been associated with decreased bone mineral density in men with prostate cancer. Some evidence suggests that there is no impact on fracture risk despite this bone mineral density loss. Our study aimed to quantify changes in bone mineral density in men with high risk prostate cancer on long-term androgen deprivation therapy and calcium and vitamin D supplementation. MATERIALS AND METHODS: Bone mineral density analysis was conducted for localized high risk prostate cancer patients enrolled in the phase III randomized trial PCS-V (Prostate Cancer Study 5), comparing conventional and hypofractionated radiation therapy. Patients received 28 months of luteinizing hormone-releasing hormone agonist and calcium and vitamin D supplementation (500 mg calcium BID+400 IU vitamin D3 BID). The areal density and T-scores (spine, femoral neck and total femur) at baseline and 30 months of followup were extracted, and the absolute change was calculated. Clinical bone density status (normal, osteopenia, osteoporosis) was monitored. RESULTS: The lumbar spine, femoral neck and total femoral bone mineral density were measured for 226, 231, and 173 patients, respectively. The mean percent change in bone mineral density was -2.65%, -2.76% and -4.27% for these respective sites (p <0.001 for all). The average decrease in bone mineral density across all sites was -3.2%, with no decline in bone mineral density category in most patients (83%). Eight patients (4%) became osteoporotic. CONCLUSIONS: Despite a mild decline in bone mineral density, the change in clinical bone mineral density category remained low with long-term androgen deprivation therapy. Consequently, calcium and vitamin D supplementation alone may suffice for most localized prostate cancer patients on long-term androgen deprivation therapy.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Densidade Óssea , Hormônio Liberador de Gonadotropina/agonistas , Nitrilas/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/fisiopatologia , Compostos de Tosil/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Humanos , Leuprolida , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
13.
Clin Adv Hematol Oncol ; 19(2): 108-118, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33596192

RESUMO

Recent population-based studies suggest that the incidence of advanced and metastatic prostate cancer may be increasing. Concurrently with this apparent stage migration toward advanced disease, several major developments have occurred in the treatment paradigm for men with advanced prostate cancer. These include the US Food and Drug Administration approval of 8 novel agents over the last decade. In addition to novel pharmaceuticals, rapidly evolving diagnostic tools have emerged. This review provides a primer for clinicians who treat men with advanced prostate cancer, including medical oncologists, radiation oncologists, and urologists.


Assuntos
Adenocarcinoma/terapia , Neoplasias da Próstata/terapia , Terapias em Estudo , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/secundário , Androstenos/uso terapêutico , Benzamidas/uso terapêutico , Ensaios Clínicos como Assunto , Terapia Combinada , Diagnóstico por Imagem/métodos , Gerenciamento Clínico , Docetaxel/uso terapêutico , Humanos , Masculino , Estudos Multicêntricos como Assunto , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Medicina de Precisão , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/terapia , Radioterapia Adjuvante , Rádio (Elemento)/uso terapêutico , Taxoides/uso terapêutico
14.
Clin Nucl Med ; 46(7): 582-583, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33630794

RESUMO

ABSTRACT: Radioligand therapy with 177Lu-PSMA-617 has emerged as a promising treatment modality for patients with mCRPC (metastatic castration resistant prostate cancer). However, genomic defects in DNA damage repair mechanisms have been proposed to affect the radiosensitivity of prostate cancers. Patients harboring such deleterious mutations are, thus, unlikely to respond to 177Lu-PSMA-617 alone and would need a more tailored therapeutic approach. We report the case of a 68-year-old man with ATM mutation-positive mCRPC who showed exceptional response to concomitant administration of enzalutamide with 177Lu-PSMA-617.


Assuntos
Benzamidas/uso terapêutico , Dipeptídeos/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Idoso , Humanos , Ligantes , Masculino , Metástase Neoplásica , Neoplasias de Próstata Resistentes à Castração/patologia , Resultado do Tratamento
15.
J Urol ; 205(6): 1689-1697, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33502237

RESUMO

PURPOSE: We report on the post-radical prostatectomy outcomes of patients enrolled in 3 randomized, multicenter, clinical trials of intense neoadjuvant androgen deprivation therapy prior radical prostatectomy. MATERIALS AND METHODS: All patients included were enrolled in trials evaluating intense androgen deprivation therapy followed by radical prostatectomy. The primary end point was time to biochemical recurrence, defined as the time from radical prostatectomy to prostate specific antigen >0.1 ng/ml or start of first post-radical prostatectomy therapy, stratified by pathological response at radical prostatectomy (presence or absence of exceptional pathological response defined as residual tumor at radical prostatectomy measuring 0-5 mm). Secondary end points included metastasis-free survival, overall survival, and time to testosterone recovery. RESULTS: Overall, 117 patients were included in the analysis, of whom 78.6% (92) had high risk disease. Following neoadjuvant therapy, 21.4% (25) had 0-5 mm of residual tumor, including 9.4% (11) with a pathological complete response. Overall, 49 patients (41.9%) experienced biochemical recurrence and the 3-year biochemical recurrence-free rate was 59.1% (95% CI 49.0-67.9). Of the 25 patients with an exceptional pathological response, 2 patients (8.0%) developed biochemical recurrence while 51.1% of nonresponders (47/92) developed biochemical recurrence. Testosterone recovery was observed in 93.8% of patients (106/113). PTEN loss and intraductal carcinoma were associated with shorter time to biochemical recurrence. CONCLUSIONS: In this pooled analysis of prospective trials, we demonstrate that exceptional pathological response following neoadjuvant therapy is associated with a favorable impact on biochemical recurrence. PTEN loss and intraductal carcinoma were associated with biochemical recurrence. Additional followup is warranted to evaluate the impact on long-term outcomes.


Assuntos
Androstenos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Benzamidas/uso terapêutico , Nitrilas/uso terapêutico , Feniltioidantoína/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/cirurgia , Idoso , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estudos Prospectivos , Neoplasias da Próstata/patologia , Medição de Risco , Resultado do Tratamento
16.
Prostate ; 81(3): 194-201, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33393676

RESUMO

BACKGROUND: To evaluate the possible major adverse cardiovascular events (MACE) associated with second-line hormonal therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We performed a population-based real-world cohort study of 4962 prostate cancer patients between 2014 and 2017 utilizing the Chang Gung Research Database of Taiwan. The second-line hormonal therapies included enzalutamide and abiraterone acetate. The outcomes of interest were MACE, including acute coronary syndrome (ACS), ischemic stroke (IS), and heart failure (HF) events that resulted in hospitalization. Cox proportional-hazards models with inverse probability of treatment weighting (IPTW) with propensity scores were used. RESULTS: After IPTW, 288 patients were prescribed second-line hormonal therapy and 1575 received first-line androgen-deprivation therapy (ADT). Of all patients diagnosed with MACE, the event rates were 2.92% in the second-line hormonal group and 2.22% in the first-line ADT group. The mean follow-up period was 9.52 months for the second-line hormonal group. Patients who received second-line hormonal therapy exhibited a significantly increased risk for MACE (hazard ratio [HR]: 3.15; 95% confidence interval [CI]: 2.03-4.89), ACS (HR: 4.94; 95% CI: 2.36-10.33), and HF (HR: 2.83; 95% CI: 1.53-5.25), compared with the first-line ADT group, but a similar risk for IS was observed in both groups (HR: 1.70; 95% CI: 0.95-3.04). CONCLUSIONS: The real-world evidence study revealed increased risks for MACE in mCRPC patients receiving second-line hormonal therapy.


Assuntos
Doenças Cardiovasculares/epidemiologia , Metástase Neoplásica/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Acetato de Abiraterona/efeitos adversos , Acetato de Abiraterona/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/uso terapêutico , Benzamidas/efeitos adversos , Benzamidas/uso terapêutico , Estudos de Coortes , Humanos , Masculino , Pessoa de Meia-Idade , Nitrilas/efeitos adversos , Nitrilas/uso terapêutico , Feniltioidantoína/efeitos adversos , Feniltioidantoína/uso terapêutico , Neoplasias de Próstata Resistentes à Castração/patologia , Fatores de Risco , Inibidores da Síntese de Esteroides , Taiwan/epidemiologia , Resultado do Tratamento
17.
JAMA Netw Open ; 4(1): e2034633, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33496795

RESUMO

Importance: Black patients have been underrepresented in prospective clinical trials of advanced prostate cancer. This study evaluated the efficacy of enzalutamide compared with bicalutamide, with planned subset analysis of Black patients with metastatic hormone-sensitive prostate cancer (mHSPC), which is a disease state responsive to androgen deprivation therapy (ADT). Objective: To compare the efficacy of enzalutamide vs bicalutamide in combination with ADT in men with mHSPC, with a subset analysis of Black patients. Design, Setting, and Participants: In this randomized clinical trial, a phase 2 screening design enabled a nondefinitive comparison of the primary outcome by treatment. Patients were stratified by race (Black or other) and bone pain (present or absent). Accrual of at least 30% Black patients was required. This multicenter trial was conducted at 4 centers in the US. Men with mHSPC with no history of seizures and adequate marrow, renal, and liver function were eligible. Data analysis was performed from February 2019 to March 2020. Interventions: Participants were randomized 1:1 to receive oral enzalutamide (160 mg daily) or bicalutamide (50 mg daily) in addition to ADT. Main Outcomes and Measures: The primary end point was the 7-month prostate-specific antigen (PSA) response (SMPR) rate, a previously accepted surrogate for overall survival (OS) outcome. Secondary end points included adverse reactions, time to PSA progression, and OS. Results: A total of 71 men (median [range] age, 65 [51-86] years) were enrolled; 29 (41%) were Black, 41 (58%) were White, and 1 (1%) was Asian. Thirty-six patients were randomized to receive enzalutamide, and 35 were randomized to receive bicalutamide. Twenty-six patients (37%) had bone pain and 37 patients (52%) had extensive disease. SMPR was achieved in 30 of 32 patients (94%; 95% CI, 80%-98%) taking enzalutamide and 17 of 26 patients (65%; 95% CI, 46%-81%) taking bicalutamide (P = .008) (difference, 29%; 95% CI, 5%-50%). Among Black patients, the SMPR was 93% (95% CI, 69%-99%) among those taking enzalutamide and 42% (95% CI, 19%-68%) among those taking bicalutamide (P = .009); among non-Black patients, the SMPR was 94% (95% CI, 74%-99%) among those taking enzalutamide and 86% (95% CI, 60%-96%) among those taking bicalutamide. The 12-month PSA response rates were 84% with enzalutamide and 34% with bicalutamide. Conclusions and Relevance: The findings of this randomized clinical trial comparing enzalutamide with bicalutamide suggest that enzalutamide is associated with improved outcomes compared with bicalutamide, in terms of the rate and duration of PSA response, in Black patients with mHSPC. Trial Registration: ClinicalTrials.gov Identifier: NCT02058706.


Assuntos
Afro-Americanos , Antagonistas de Androgênios/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Nitrilas/uso terapêutico , Feniltioidantoína/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Compostos de Tosil/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Feniltioidantoína/uso terapêutico , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/etnologia , Resultado do Tratamento
18.
Cancer Res ; 81(6): 1583-1594, 2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33483372

RESUMO

Ferroptosis is a type of programmed cell death induced by the accumulation of lipid peroxidation and lipid reactive oxygen species in cells. It has been recently demonstrated that cancer cells are vulnerable to ferroptosis inducers (FIN). However, the therapeutic potential of FINs in prostate cancer in preclinical settings has not been explored. In this study, we demonstrate that mediators of ferroptosis, solute carrier family 7 member 11, SLC3A2, and glutathione peroxidase, are expressed in treatment-resistant prostate cancer. We further demonstrate that treatment-resistant prostate cancer cells are sensitive to two FINs, erastin and RSL3. Treatment with erastin and RSL3 led to a significant decrease in prostate cancer cell growth and migration in vitro and significantly delayed the tumor growth of treatment-resistant prostate cancer in vivo, with no measurable side effects. Combination of erastin or RSL3 with standard-of-care second-generation antiandrogens for advanced prostate cancer halted prostate cancer cell growth and migration in vitro and tumor growth in vivo. These results demonstrate the potential of erastin or RSL3 independently and in combination with standard-of-care second-generation antiandrogens as novel therapeutic strategies for advanced prostate cancer. SIGNIFICANCE: These findings reveal that induction of ferroptosis is a new therapeutic strategy for advanced prostate cancer as a monotherapy and in combination with second-generation antiandrogens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carbolinas/farmacologia , Ferroptose/efeitos dos fármacos , Piperazinas/farmacologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Sistema y+ de Transporte de Aminoácidos/metabolismo , Antagonistas de Androgênios/farmacologia , Antagonistas de Androgênios/uso terapêutico , Androstenos/farmacologia , Androstenos/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzamidas/farmacologia , Benzamidas/uso terapêutico , Carbolinas/uso terapêutico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Cadeia Pesada da Proteína-1 Reguladora de Fusão/metabolismo , Humanos , Masculino , Camundongos , Estadiamento de Neoplasias , Nitrilas/farmacologia , Nitrilas/uso terapêutico , Feniltioidantoína/farmacologia , Feniltioidantoína/uso terapêutico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Piperazinas/uso terapêutico , Próstata/patologia , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
20.
BMC Infect Dis ; 21(1): 82, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461505

RESUMO

BACKGROUND: Keratitis due to by filamentous fungi are not easy to diagnose thus causing a delay in correct therapy. There are many descriptions of keratitis due to Candida, Fusarium and Aspergillus genera. Subramaniula genus has only recently been reported to cause human infections and there are few descriptions of eye infections due to this filamentous fungus. Diagnosis of fungal keratitis is usually based on microscopic and cultural techniques of samples obtained by corneal swabbing or scraping. Considering the amount of time required to obtain culture results it is wise to use other diagnostic methods, such as molecular analyses. Therapeutic options against these fungi are limited by low tissue penetration in the eye due to ocular barriers. We describe the first case of S. asteroides human keratitis treated with isavuconazole. CASE PRESENTATION: We describe a rare case of fungal keratitis unresponsive to antimicrobial treatment in a 65-year-old male patient without a history of diabetes or immunological diseases. He reported that the onset of symptoms occurred during a long holiday in Cape Verde Island. Initial treatment with topical antibiotics associated to steroids were ineffective, allowing a slow clinical progression of disease to corneal perforation. On admission in our Hospital, slit-lamp examination of the left eye showed conjunctival congestion and hyperemia, a large inferior corneal ulceration with brown pigment, corneal edema, about 3 mm of hypopyon and irido-lenticular synechiae. The slow clinical progression of the disease to corneal perforation and the aspect of the ulcer were consistent with a mycotic etiology. Molecular methods used on fungal colonies isolated by Sabouraud's dextrose agar cultures allowed the identification of Subramaniula asteroids from corneal scraping. Antimicrobial test showed a good susceptibility of this filamentous fungus to voriconazole and isavuconazole. Moreover, this fungal keratitis was successfully treated with isavuconazole, without side effects, observing a progressive clinical improvement. CONCLUSIONS: Molecular methods may be useful for the identification of filamentous fungal keratitis on scraping samples thus shortening the time of diagnosis. Systemic therapy by isavuconazole could be useful to treat the filamentous fungal keratitis, reducing the possible adverse effects due to the use of voriconazole by systemic administration.


Assuntos
Úlcera da Córnea/diagnóstico , Infecções Oculares Fúngicas/diagnóstico , Sordariales/isolamento & purificação , Idoso , Antifúngicos/administração & dosagem , Antifúngicos/uso terapêutico , Úlcera da Córnea/tratamento farmacológico , Úlcera da Córnea/microbiologia , Diagnóstico Diferencial , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Humanos , Masculino , Nitrilas/administração & dosagem , Nitrilas/uso terapêutico , Soluções Oftálmicas , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Triazóis/administração & dosagem , Triazóis/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...