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1.
Anticancer Res ; 39(9): 5165-5170, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519629

RESUMO

BACKGROUND/AIM: Daratumumab is a promising novel agent for relapsed/refractory multiple myeloma (RRMM). However, there are limited data on its efficacy and toxicity profiles in real-world patients, especially in the Asian population. PATIENTS AND METHODS: This was a multicenter, retrospective, longitudinal cohort study set between January 2017 and April 2019. We collected and analyzed clinical and survival data of 21 patients treated with daratumumab monotherapy. All patients were previously exposed to proteasome inhibitors and immunomodulatory drugs. RESULTS: The overall response rate was 42.1%, including one complete remission (4.8%) and three very good partial responses (14.3%). The cycles of daratumumab delivered were three (range=1-10 cycles) and the median progression-free survival was 6 months, while the overall survival was not reached. Infusion reaction was observed in nine patients (42.9%), and one discontinued permanently. Fatigue was the most common adverse event (52.4%), and there were five cases of documented infection during daratumumab treatment, two of them leading to the death of the patient. CONCLUSION: Daratumumab monotherapy showed fairly promising activity with modest tolerance in heavily treated Asian RRMM patients.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Mieloma Múltiplo/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Ásia , Linhagem Celular Tumoral , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
2.
J Cancer Res Clin Oncol ; 145(9): 2303-2311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31396700

RESUMO

BACKGROUND: Since 1997, several monoclonal antibodies (mAbs) targeting the same receptor or its ligand have been approved for use in oncology. However, no studies have summarized head-to-head trials of these mAbs. METHODS: Systematic search of the biomedical literature and ClinicalTrials.gov for randomized studies comparing mAbs targeting the same receptor or its ligand that have been completed and published, completed and unpublished, or ongoing. We extracted trial characteristics including phase, indication, enrollment or target enrollment, randomization, primary endpoint and sponsor. RESULTS: Twenty-two approved cancer mAbs had at least one other approved mAb targeting the same receptor or its ligand, totaling 41 different oncology indications. These include 5 anti-CD20 mAbs, 5 anti-PD1/PDL1 mAbs, 4 anti-HER2 mAbs, 3 anti-EGFR mAbs, 3 anti-VEGF mAbs and 2 anti-IL6/IL6R mAbs. Seventeen were completed and published and 14 were unpublished or ongoing trials. The completed and published trials enrolled 11,373 patients and tested 13 mAbs (13/22, 59%). Additionally, 13 (76%) contained drugs manufactured by the same company and 13 (76%) reached conclusions felt to be favorable to the sponsor. Of the 14 ongoing/completed unpublished trials, there is a total target enrollment of 3404 patients with 9 mAbs tested. Of these, 86% (12/14) are testing mAbs manufactured by the same company and 71% (10/14) are sponsored by the company that made the drug being tested. CONCLUSIONS: Most trials test drugs manufactured or sponsored by the same company. An overview of clinical trials agenda may lead to more uniform testing, helping clinicians make better evidence-informed prescribing decisions.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Ensaios Clínicos como Assunto/estatística & dados numéricos , Neoplasias/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Aprovação de Drogas , Humanos , Neoplasias/epidemiologia , Estados Unidos/epidemiologia , United States Food and Drug Administration
3.
Drugs Today (Barc) ; 55(8): 485-494, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31461085

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent type of malignancy in Caucasians worldwide. Several factors have been correlated with aggressiveness and likelihood of recurrence and distant metastases, which are challenging to control. Metastatic disease has a dismal prognosis, and standard chemotherapy has failed to significantly improve outcomes. Recently, it has been recognized that cSCCs are highly mutated tumors with a denoting potential likelihood of response to immune checkpoint blockade. Cemiplimab is an anti-programmed cell death protein 1 (PD-1) antibody recently approved for the treatment of unresectable locally advanced or metastatic cSCC by the U.S. Food and Drug Administration (FDA) and the European Commission with a compelling response rate and an acceptable safety profile.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia
4.
Presse Med ; 48(7-8 Pt 1): 859-870, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447331

RESUMO

Non-follicular small cell lymphomas include several entities whose clinical and pathological descriptions have been refined in the last 20 years. MALT lymphoma, developed at the expense of lymphoid tissue associated with the mucosa, is usually localized to a given organ, but can also disseminate. Some patients with MALT lymphoma can be treated by eradicating the associated infectious agent, whereas local treatment should be preferred for other cases ; disseminated forms and relapsed patients are eligible for anti-CD20 antibodies associated with cytotoxic agents. Patients with mantle cell lymphoma have benefited from many advances, including the use of cytarabine and bendamustine, anti-CD20 antibodies, intensive treatments (autograft) and recently targeted therapy (ibrutinib, inhibitor or the Bruton tyrosine kinase). Patients with splenic nodal marginal zone lymphomas should be evaluated for different options, of which immunochemotherapy remains important. For all these entities, the implementation of treatments may be delayed by several years for certain groups of patients. Although considered as incurable, the prognosis of these pathologies has improved significantly and the majority of patients will be able to live for many years with often treatment-free intervals.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Fatores Etários , Idade de Início , Anticorpos Monoclonais/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunoterapia/métodos , Imunoterapia/tendências , Linfoma de Zona Marginal Tipo Células B/classificação , Linfoma de Zona Marginal Tipo Células B/diagnóstico , Linfoma de Zona Marginal Tipo Células B/epidemiologia , Linfoma de Zona Marginal Tipo Células B/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Prognóstico , Neoplasias Esplênicas/diagnóstico , Neoplasias Esplênicas/epidemiologia , Neoplasias Esplênicas/patologia , Neoplasias Esplênicas/terapia , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia
5.
Presse Med ; 48(7-8 Pt 1): 807-815, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447332

RESUMO

Chronic lymphocytic leukemia is the most frequent adult leukemia. Eighty per cent of the patients are asymptomatic at diagnosis and 30% of the patients will be never treated. The diagnosis is based on the blood smear examination and immunophenotyping by flow cytometry of blood lymphocytes. The first line option is immunochemotherapy in 90% of the patients without genetic abnormalities associated with chemo resistance. The use of new compounds targeting different pathways is more frequent especially in relapsing patients and could be an alternative to the chemotherapy in the future. Asymptomatic patients with a stable disease assessed by the specialist can be followed by the general practitioner with a blood count and clinical examination every six months or once a year.


Assuntos
Leucemia Linfocítica Crônica de Células B , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Terapias em Estudo/métodos , Terapias em Estudo/tendências
6.
Presse Med ; 48(7-8 Pt 1): 825-831, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447337

RESUMO

Diagnosis criteria have been revised in 2014 and allow the treatment of some asymptomatic patients. Since 2015, a new prognostic score includes tumor plasma cells chromosomal abnormalities. It helps in the distinction between "standard risk" and "high risk" myelomas. Scanner, MRI and Pet Scan are the radiological reference exams to evaluate bone involvement. Alkylating agents, immunomodulators, proteasome inhibitors, and monoclonal antibodies became the most important antitumoral treatments. Risk notion will become more and more important for therapeutic choices. These choices will depend on residual disease evaluation. The next decade will be the immunotherapies development decade.


Assuntos
Detecção Precoce de Câncer/tendências , Oncologia/tendências , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Terapias em Estudo/tendências , Anticorpos Monoclonais/uso terapêutico , Terapia Combinada/tendências , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/métodos , Imunoterapia/tendências , Oncologia/métodos , Oncologia/normas , Mieloma Múltiplo/patologia , Guias de Prática Clínica como Assunto , Prognóstico , Terapias em Estudo/métodos
7.
Acta Gastroenterol Belg ; 82(2): 322-325, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314196

RESUMO

Colorectal cancer is one of the most frequently diagnosed malignancies worldwide. One of the most important developments in the management of metastatic colorectal cancer is targeted therapy. Bevacizumab, a monoclonal antibody inhibiting VEGF induced angiogenesis, has been accepted as safe and efficient in the treatment of metastatic colorectal cancer for more than a decade. Addition of bevacizumab to fluorouracil-based chemotherapy is also associated with severe adverse events. We present a case of bevacizumab-induced bowel ischaemia associated with gastrointestinal haemorrhage.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Metástase Neoplásica/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Hemorragia Gastrointestinal , Humanos
8.
N Engl J Med ; 381(2): 132-141, 2019 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-31291515

RESUMO

BACKGROUND: Episodic cluster headache is a disabling neurologic disorder that is characterized by daily headache attacks that occur over periods of weeks or months. Galcanezumab, a humanized monoclonal antibody to calcitonin gene-related peptide, may be a preventive treatment for cluster headache. METHODS: We enrolled patients who had at least one attack every other day, at least four total attacks, and no more than eight attacks per day during a baseline assessment, as well as a history of cluster headache periods lasting at least 6 weeks, and randomly assigned them to receive galcanezumab (at a dose of 300 mg) or placebo, administered subcutaneously at baseline and at 1 month. The primary end point was the mean change from baseline in the weekly frequency of cluster headache attacks across weeks 1 through 3 after receipt of the first dose. The key secondary end point was the percentage of patients who had a reduction from baseline of at least 50% in the weekly frequency of cluster headache attacks at week 3. Safety was also assessed. RESULTS: Recruitment was halted before the trial reached the planned sample size of 162 because too few volunteers met the eligibility criteria. Of 106 enrolled patients, 49 were randomly assigned to receive galcanezumab and 57 to receive placebo. The mean (±SD) number of cluster headache attacks per week in the baseline period was 17.8±10.1 in the galcanezumab group and 17.3±10.1 in the placebo group. The mean reduction in the weekly frequency of cluster headache attacks across weeks 1 through 3 was 8.7 attacks in the galcanezumab group, as compared with 5.2 in the placebo group (difference, 3.5 attacks per week; 95% confidence interval, 0.2 to 6.7; P = 0.04). The percentage of patients who had a reduction of at least 50% in headache frequency at week 3 was 71% in the galcanezumab group and 53% in the placebo group. There were no substantial between-group differences in the incidence of adverse events, except that 8% of the patients in the galcanezumab group had injection-site pain. CONCLUSIONS: Galcanezumab administered subcutaneously at a dose of 300 mg once monthly reduced the weekly frequency of attacks of episodic cluster headache across weeks 1 through 3 after the initial injection, as compared with placebo. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT02397473.).


Assuntos
Analgésicos/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Cefaleia Histamínica/prevenção & controle , Adulto , Analgésicos/administração & dosagem , Analgésicos/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Placebos/uso terapêutico
9.
Medicine (Baltimore) ; 98(27): e16236, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277139

RESUMO

Ramucirumab is a human immunoglobulin G1 monoclonal antibody that binds to vascular endothelial growth factor receptor 2 and is used for the treatment of metastatic or inoperable gastric, colorectal, and non-small cell lung cancers. However, ramucirumab can result in renal adverse events, including nephrotic syndrome, and the clinical course of this event is unclear. This study aimed to investigate the clinical course and pathological findings of patients with nephrotic syndrome after ramucirumab treatment.We evaluated 5 patients with malignancies (2 cases of gastric cancer and 3 cases of colorectal cancer) who developed nephrotic syndrome during treatment with ramucirumab. Two patients were diagnosed based on renal biopsy. We investigated the relationship between ramucirumab treatment and clinical courses, pathological findings, and renal outcomes.Four of 5 patients developed nephrotic syndrome after 1 or 2 doses of ramucirumab. All patients had hypertension, and 2 of 5 patients had renal dysfunction, defined as an increase in serum creatinine levels of ≥50% or ≥0.3 mg/dL. The 2 renal biopsy samples revealed a diffuse glomerular basement membrane double contour, intracapillary foam cell infiltration, and partial foot process effacement. Early drug discontinuation and antihypertensive therapy improved proteinuria, renal dysfunction, and hypertension in all patients.Nephrotic syndrome is a renal adverse event observed in cancer patients after ramucirumab treatment. We suggest that urinalysis, renal function, and blood pressure should be closely monitored in patients undergoing ramucirumab treatment, and treatment should be discontinued if renal adverse events are detected.


Assuntos
Anticorpos Monoclonais/efeitos adversos , Neoplasias/tratamento farmacológico , Síndrome Nefrótica/induzido quimicamente , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Humanos
10.
Arerugi ; 68(6): 701-706, 2019.
Artigo em Japonês | MEDLINE | ID: mdl-31308337

RESUMO

Defects in the skin's barrier function are known to make it more likely for skin and soft tissue infection to occur in association with atopic dermatitis. These secondary infections sometimes develop into systemic infections such as bacteremia. Here, we report on our use of anti-IL-4/13 monoclonal antibody (dupilumab) on two cases with atopic dermatitis that was refractory to conventional management techniques and who had a history of serious infection (bacteremia and associated sternal osteomyelitis, infective endocarditis) caused by Staphylococcus aureus. Both cases had underlying congenital heart disease. The dermatological symptoms of both cases showed marked improvement at 16 weeks after the start of dupilumab use. The use of dupilumab on atopic dermatitis may lead to less risk of infection of skin and soft tissues deveroping serious infections due to an underlying congenital disease. When determining the treatment strategy, the cooperation of specialists in a variety of fields as well as the primary care physician was important.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Cardiopatias/congênito , Bacteriemia , Humanos
11.
Anticancer Res ; 39(7): 3917-3921, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262921

RESUMO

AIM: To evaluate the efficacy and safety of re-treatment with anti-programmed death (PD)-L1 antibody (atezolizumab) after anti-PD-1 antibody (nivolumab/pembrolizumab) treatment in advanced non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: We retrospectively reviewed 18 NSCLC patients who received atezolizumab after anti-PD-1 antibody treatment. Data on patient characteristics, number of cycles of anti-PD-1 antibody and atezolizumab, regimens between anti-PD-1 antibody and atezolizumab, best response, and immune-related adverse events (irAEs) were collected and analyzed. RESULTS: Nine patients a had high (≥50%) PD-L1 expression. The median number of cycles of atezolizumab was 3 (range=2-7). The median progression-free survival was 2.9±1.8 months. Seven (38.9%) and 11 (61.1%) patients had stable and progressive disease, respectively. No patient achieved partial or complete response. There were no significant differences in the occurrence of irAEs between anti-PD-1 antibodies and atezolizumab. CONCLUSION: Preliminary results showed that patients previously treated with anti PD-1 antibodies received only limited benefit from subsequent atezolizumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/imunologia , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
12.
Anticancer Res ; 39(7): 3961-3965, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262928

RESUMO

BACKGROUND/AIM: Immune check point inhibitors (ICIs) are changing cancer treatment in several malignancies, including non-small cell lung cancer (NSCLC). The introduction of these active new agents is associated with a relevant increase of costs and it is, therefore, important to create a balance between the costs of treatment and the added value represented by the improvement of the clinical parameters of interest such as overall survival (OS). This analysis was conducted to assess the pharmacological costs of first- and second-line treatments with ICIs (pembrolizumab, nivolumab and atezolizumab) for metastatic NSCLC. MATERIALS AND METHODS: The present evaluation was restricted to phase III randomized controlled trials (RCTs). We calculated the pharmacological costs necessary to get the benefit in OS. RESULTS: Six phase III RCTs were evaluated. Concerning first-line, the lowest cost per month of OS-gain was associated with the use of pembrolizumab at 2,734 €. Concerning second-line, the lowest cost per month of OS-gain was associated with the use of atezolizumab at 3,724 €. CONCLUSION: Pembrolizumab and atezolizumab are cost-effective in both first and second-line treatment for metastatic NSCLC, respectively.


Assuntos
Anticorpos Monoclonais Humanizados/economia , Anticorpos Monoclonais/economia , Antineoplásicos Imunológicos/economia , Carcinoma Pulmonar de Células não Pequenas/economia , Neoplasias Pulmonares/economia , Nivolumabe/economia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Ensaios Clínicos Fase III como Assunto , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
Neuquém; Gobierno de la Provincia del Neuquém; jul. 2019.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-1017097

RESUMO

INTRODUCCIÓN: Los linfomas son neoplasias del sistema linfático. Se dividen en los linfomas de Hodgkin y linfomas no Hodgkin (LNH). El linfoma de Hodgkin (LH) es una neoplasia linfoproliferativa B clonal, potencialmente curable. Las tasas de supervivencia han mejorado en las últimas décadas gracias a las distintas opciones terapéuticas. La supervivencia relativa se calcula en 92% al año, 85% a los 5 años y 80% a los 10 años del diagnóstico. En Argentina, la incidencia calculada del linfoma Hodgkin es 1,5/100.000 habitantes. Los Linfomas No Hodking (LNH) son un grupo heterogéneo de linfomas T y B cuya incidencia en Argentina es de 7,4/100.000 habitantes. El Linfoma Anaplásico de Células Grandes (LACG) es un tipo infrecuente de linfoma cutáneo tipo T (representa el 5% de los LNH) y expresan uniformemente CD30. TECNOLOGÍAS SANITARIA DE INTERÉS: El brentuximab es un anticuerpo monoclonal anti-CD30, se une a CD30 en la superficie de las células del linfoma y se internaliza rápidamente provocando la interrupción del ciclo celular y la apoptosis. METODOLOGÍA: Se realizó una búsqueda no sistemática de bibliografía científica priorizando la inclusión de revisiones sistemáticas y metaanálisis, evaluaciones de tecnologías sanitarias e informes de seguridad, guías de Práctica Clínica basadas en la evidencia. RESULTADOS: Del ERC en pacientes LH recurrente refractario luego de TAMO, con riesgo de progresión no se hallaron diferencias en la sobrevida global al momento del análisis (HR = 1.12, IC 95% = [0.69; 1.82]) en el grupo tratado con brentuxumab. El anàlisis posterior del mismo estudio a los 5 años mostro que la SLP a 5 años fue del 59% (IC 95%, 51-66) con BV frente al 41% (IC95%, 33-49) con placebo (HR 0,521; IC 95%, 0,379 -0.717). Los estudios observacionales en linfoma Hodking clasico refractario o en recaida son de una sola rama y de baja calidad metodològica, donde no se puede evidenciar comparaciones directas. El estudio observacional más importante Europeo que involucra a mas de 400 pacientes con LH clásico concluye que BV pre-aloinjerto no tuvo impacto en la enfermedad aguda de injerto contra huésped (GVHD), la mortalidad sin recidiva, la incidencia acumulada de recaída, la SLP o SG y solo redujo el riesgo de GVHD crónica (relación de riesgo = 0 · 64; IC 95% = 0 · 45-0 · 92; P <0 · 02). CONCLUSIÓN: La evidencia científica encontrada es de baja calidad. El uso de Brentuximab Vedotina en el linfoma Hodking clássico refractário o recaído y en el linfoma anaplásico de células grandes sistêmico refractário o recaído no ha sido estudiado comparado con las alternativas disponibles en la mayoría de los casos. En estos, ha demostrado una alta tasa de respuestas, pero su impacto en la sobrevida global y en la calidad de vida es incierto. El uso de desenlaces intermedios, como la respuesta completa o la sobrevida libre de progresión, podrían encontrarse potencialmente afectados por sesgos asociados con el investigador. Por otro lado, estos desenlaces subrogados no han demostrado ser predictores de una mejor calidad de vida o una mayor sobrevida global. Brentuximab Vedotina presenta efectos adversos, un elevado costo, costo de oportunidad y potencial impacto en la equidad. Ante las limitadas opciones terapéuticas y el mal pronostico de estos pacientes, la mayoría de las sociedades internacionales y financiadores de salud de países de alto ingresos lo consideran una alternativa válida. En contextos similares al nuestro, no es recomendado por Agencias de Evaluación de Tecnologías Sanitarias de Uruguay ni de Perú. En Argentina recomendaron no cubrir Brentuximab Vedotina el Instituto de Efectividad Clínica y Sanitaria (IECS), el Instituto Nacional del Cáncer ni la COSSSPRA (Obras Sociales Provinciales). No es cubierto por el Ministerio de Desarrollo Social de Nación Argentina.


Assuntos
Humanos , Linfoma não Hodgkin/tratamento farmacológico , Doença de Hodgkin/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Argentina , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício/economia
14.
Curr Opin Ophthalmol ; 30(5): 401-406, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31313753

RESUMO

PURPOSE OF REVIEW: To offer an update on advances and controversies in the assessment, investigation and treatment of thyroid eye disease (TED), a disfiguring orbital autoimmune disease, which can manifest with diplopia and threaten not only sight - but also life. RECENT FINDINGS: Developments in biomarkers and imaging are helping to tailor the management of patients. Emerging therapies target different pathways in the disease and are informed by studies into TED pathogenesis: the last 2 years has, for example, seen the culmination of a two-decade long bench-to-bedside story in which an original focus on the IGF1 receptor has translated into an effective treatment for proptosis in thyroid eye disease. Whether this will result in a real-world reduction in TED-related morbidity will depend on access; commercial pricing decisions may preclude widespread adoption of novel therapies. SUMMARY: Thyroid eye disease research is enjoying a renaissance with advances in both monitoring and treatment coupled with a renewed emphasis on a holisitic approach, which includes aesthetic care for patients; this is perhaps the most exciting time to be part of the international thyroid eye disease community in decades - for physicians, surgeons and patients. The commercial window for break-through drugs are narrowing with an array of new therapeutic agents in the pipeline over the coming decade.


Assuntos
Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/terapia , Anticorpos Monoclonais/uso terapêutico , Descompressão Cirúrgica , Humanos , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Ácido Micofenólico/uso terapêutico , Sirolimo/uso terapêutico
15.
Artigo em Chinês | MEDLINE | ID: mdl-31315359

RESUMO

Objective: To observe the effect of tumor necrosis factor-α (TNF-α) monoclonal antibody on autophagy in allergic rhinitis (AR) mice. Methods: Thirty six weeks old BALB/c mice were randomly divided by random number table method into five groups: control group, model group (AR group), TNF-α antibody intervention group (AR+TNF-α group), autophagy inhibitor (3-methylindole, 3-NA) intervention group (AR+3-MA group), TNF-α antibody combined with autophagy inducer rapamycin (RAP) intervention group (AR+TNF-α+RAP group), with 6 mice in each group. AR model was established by conventional method, the corresponding reagent was administered before nasal cavity stimulation sensitization and during the whole experiment. Behavioral scores of mice were obtained, blood was collected from the eye socket, and mice in each group were sacrificed to collect nasal mucosa tissue samples. Pathological changes of nasal mucosa were observed by hematoxylin-eosin staining. Expression levels of inflammatory factor and IgE in serum were detected by enzyme-linked immunosorbent assay (ELISA). Expressions of autophagy related indicators microtubule-associated protein-1 light chain-3B (LC3B), Beclin-1, sequestosome1 (p62), autophagy-related 5 (ATG5), autophagy-related 7 (ATG7) were measured by Real-time PCR and Western blot. The aggregation of LC3B protein was observed by immunofluorescence. SPSS 19.0 software was used for statistical analysis. Results: Compared with the AR model group, symptoms of AR in AR+TNF-α group and AR+3-MA group were mild; the pathological changes of nasal mucosa were weak; the expression of IgE, TNF-α, interleukin 4 (IL-4), interferon-γ (IFN-γ) in serum significantly reduced (IgE: 666.19±78.35 (x±s) vs. 692.38±64.29 vs. 1 059.05±146.44, TNF-α: 112.06±12.95 vs. 113.17±15.43 vs. 161.22±17.96, IL-4: 54.05±7.14 vs. 58.26±5.67 vs. 79.95±6.33, IFN-γ: 28.58±4.51 vs. 30.67±2.60 vs. 39.83±3.31, all P<0.05), and the expression of LC3B Ⅱ/Ⅰ, Beclin-1, ATG5, ATG7 in nasal mucosa significantly decreased, the expression of p62 significantly elevated. After intervention with autophagy inducer RAP, the therapeutic effect of TNF-α monoclonal antibodies on AR was antagonized. Conclusion: TNF-α monoclonal antibody significantly improves nasal symptoms in AR mice by inhibiting autophagy levels.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Autofagia/imunologia , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos BALB C
16.
Cancer Immunol Immunother ; 68(8): 1359-1368, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31332464

RESUMO

Immune checkpoint inhibitors targeting coinhibitory pathways in T cells possess efficacy in combating cancer. In addition to PD-1/PD-L1 and CTLA-4 antibodies which are already established in tumor immunotherapy, immune checkpoints such as LAG-3 or BTLA are emerging, which may have the potential to enhance T-cell responses alone or in combination with PD-1 blockers. CD4+ T cells play a central role in the immune system and contribute to productive immune responses in multiple ways. The effects of immune checkpoint inhibitors on this cell subset may thus critically influence therapeutic outcomes. Here, we have used in vitro responses to tetanus toxoid (TT) as a model system to study the effects of immune checkpoint inhibitors on CD4+ T-cell responses. CFSE-labeled PBMCs of 65 donors were stimulated with TT in the presence of blocking antibodies to PD-L1, CTLA-4, LAG-3, or BTLA for 7 days. We found that the PD-L1 antibody greatly enhanced cytokine production and antigen-specific CD4+ T-cell proliferation, whereas blocking antibodies to BTLA or LAG-3 did not augment responses to TT. Surprisingly, the presence of the therapeutic CTLA-4 antibody ipilimumab resulted in a significant reduction of CD4+ T-cell proliferation and cytokine production. Stimulation experiments with an IgG4 variant of ipilimumab indicated that the inhibitory effect of ipilimumab was dependent on its IgG1 isotype. Our results indicate that the therapeutic CTLA-4 antibody ipilimumab can impair CD4+ effector T-cell responses and that this activity is mediated by its Fc part and CD16-expressing cells.


Assuntos
Anticorpos Monoclonais/farmacologia , Antineoplásicos/farmacologia , Linfócitos T CD4-Positivos/imunologia , Vacinas Anticâncer/imunologia , Imunoterapia/métodos , Ipilimumab/farmacologia , Neoplasias/terapia , Anticorpos Monoclonais/uso terapêutico , Antígenos CD/imunologia , Antineoplásicos/uso terapêutico , Antígeno B7-H1/imunologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Antígeno CTLA-4/imunologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Humanos , Fragmentos Fc das Imunoglobulinas/metabolismo , Ipilimumab/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Neoplasias/imunologia , Receptores Imunológicos/imunologia , Toxoide Tetânico/imunologia
17.
Cancer Treat Rev ; 78: 17-30, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31325788

RESUMO

INTRODUCTION: Immune checkpoint inhibitors, targeting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and the programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) pathways have shown remarkable potential in several types of cancer. In this review we summarize published and ongoing studies on checkpoint inhibitors in pancreatic cancer (PC). METHODS: We conducted a systematic literature search using Medline and Embase up to November 2018; additional data from a search on clinicaltrials.gov were included. Endpoints of interest encompassed overall survival (OS), progression free survival (PFS) and response rates. RESULTS: Full-length articles constituted a minority of included records. Furthermore, few patients were enrolled, and only few phase II studies were identified. Disappointing limited activity was demonstrated with single-agent checkpoint inhibitors in PC. A small number of studies on combination therapy showed promise with regards to response. But overall, PC patients treated with checkpoint inhibitors were not shown to elicit improvement in response rates or overall survival. CONCLUSION: Checkpoint inhibition monotherapy has failed to elicit efficacy in patients with pancreatic cancer. Combination regimens including chemotherapy have shown initial promise, but these results need to be verified. Numerous studies on checkpoint inhibition in PC are ongoing.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Genes cdc , Neoplasias Pancreáticas/tratamento farmacológico , Animais , Humanos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia
18.
Gan To Kagaku Ryoho ; 46(6): 1057-1059, 2019 Jun.
Artigo em Japonês | MEDLINE | ID: mdl-31273175

RESUMO

According to the REGARD and RAINBOW trials, ramucirumab(RAM)was introduced as second-line therapy for advanced or metastatic gastric cancer. Endoscopic metallic stent placement and angiogenesis inhibitor administration carry the risk of gastrointestinal perforation. The outcomes of patients who undergo endoscopic placement of metallic stents during RAM treatment have not yet been fully assessed. A 60's man was diagnosed with advanced esophagogastric junction cancer(por) with Virchow's lymph node metastases. His tumor was classified as cT4a(SE), N1(#1), M1, stage Ⅳ. He received chemotherapy, but the size of the primary tumor and metastases increased. After stenting for gastric outlet obstruction, he received a paclitaxel(PTX)plus RAM regimen as third-line treatment. Because of CTCAE Grade 2 peripheral neuropathy, PTX was discontinued after 10 courses. For 11 months, tumor control without adverse events was maintained. The patient was then switched to CPT-11 as fourth-line treatment.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Neoplasias Gástricas , Junção Esofagogástrica , Humanos , Masculino , Stents , Neoplasias Gástricas/terapia
19.
High Blood Press Cardiovasc Prev ; 26(3): 199-207, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236902

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9)-related discoveries of the turn of the century have translated into substantial novelty in dyslipidemia treatment in the last 5 years. With chronic preventable atherosclerotic cardiovascular diseases (ASCVD) representing an epidemic of morbidity and mortality worldwide, low-density lipoprotein cholesterol (LDL-c) reduction represents a public health priority. By overcoming two major statin-related issues, namely intolerance and ineffectiveness, PCSK9 inhibitors have offered a safe and effective option in selected clinical settings where LDL-c reduction is required. Herein, we recapitulate recent findings, clinical applications, and ASCVD prevention potential of PCSK9 inhibition, with focus on anti-PCSK9 monoclonal antibodies, evolocumab and alirocumab.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Anticolesterolemiantes/uso terapêutico , Aterosclerose/prevenção & controle , LDL-Colesterol/sangue , Dislipidemias/tratamento farmacológico , Pró-Proteína Convertase 9/antagonistas & inibidores , Inibidores de Serino Proteinase/uso terapêutico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticolesterolemiantes/efeitos adversos , Aterosclerose/sangue , Aterosclerose/enzimologia , Aterosclerose/epidemiologia , Biomarcadores/sangue , Dislipidemias/sangue , Dislipidemias/enzimologia , Dislipidemias/epidemiologia , Humanos , Guias de Prática Clínica como Assunto , Pró-Proteína Convertase 9/metabolismo , Fatores de Risco , Inibidores de Serino Proteinase/efeitos adversos , Resultado do Tratamento
20.
An Bras Dermatol ; 94(2 Suppl 1): 76-107, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31166402

RESUMO

Psoriasis is a chronic inflammatory disease that affects 1.3% of the Brazilian population. The most common clinical manifestations are erythematous, scaling lesions that affect both genders and can occur on any anatomical site, preferentially involving the knees, elbows, scalp and genitals. Besides the impact on the quality of life, the systemic nature of the disease makes psoriasis an independent risk factor for cardiovascular disease, especially in young patients with severe disease. By an initiative of the Brazilian Society of Dermatology, dermatologists with renowned clinical experience in the management of psoriasis were invited to form a work group that, in a partnership with the Brazilian Medical Association, dedicated themselves to create the Plaque Psoriasis Diagnostic and Treatment Guidelines. The relevant issues for the diagnosis (evaluation of severity and comorbidities) and treatment of plaque psoriasis were defined. The issues generated a search strategy in the Medline-PubMed database up to July 2018. Subsequently, the answers to the questions of the recommendations were devised, and each reference selected presented the respective level of recommendation and strength of scientific evidence. The final recommendations for making up the final text were worded by the coordinators.


Assuntos
Psoríase/diagnóstico , Psoríase/terapia , Corticosteroides/uso terapêutico , Antralina/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Brasil , Inibidores de Calcineurina/uso terapêutico , Comorbidade , Ciclosporina/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Dermatologia , Combinação de Medicamentos , Feminino , Humanos , Masculino , Metotrexato/uso terapêutico , Fototerapia/métodos , Psoríase/epidemiologia , Índice de Gravidade de Doença , Sociedades Médicas , Fatores de Tempo , Vitamina D/análise
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