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1.
Future Oncol ; 18(36): 3961-3969, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36377973

RESUMO

Treatment with covalent Bruton tyrosine kinase inhibitors (BTKi) represents an important advance in the management of relapsed or refractory mantle cell lymphoma, but these treatments are not curative and many patients ultimately relapse. Pirtobrutinib, a highly selective, noncovalent (reversible) BTKi, inhibits both wild type and C481-mutant BTK with equal low nM potency, and has favorable oral pharmacology that enables continuous BTK inhibition throughout the dosing interval regardless of intrinsic rate of BTK turnover. Pirtobrutinib is well tolerated and has demonstrated promising efficacy in patients with poor prognosis B-cell malignancies following prior therapy, including covalent BTKi. This phase III, head-to-head, randomized study (NCT04662255) will evaluate whether pirtobrutinib is superior to investigator's choice of covalent BTKi in patients with previously treated, BTKi-naive mantle cell lymphoma.


MCL is an uncommon type of B-cell non-Hodgkin lymphoma, a cancer of the immune system. It starts in the part of the lymph node called the mantle zone, where unusual B cells gather and crowd out healthy B cells in the lymph nodes, spleen, bone marrow and/or other organs. MCL can be caused by inappropriate cell signaling. BTK has been identified as a key driver of unusual cell signaling and blocking BTK has been shown to help kill the cancer cells. Covalent (not reversible) BTK inhibitors have advanced the treatment of MCL, but the effectiveness of these treatments is limited by side effects and treatment resistance. Pirtobrutinib, a noncovalent (reversible) BTK inhibitor, has been shown to have manageable side effects and to be effective in patients with MCL following previous treatment, including treatment with covalent BTK inhibitors. The BRUIN MCL-321 study compares pirtobrutinib with three currently approved covalent BTK inhibitors (ibrutinib, acalabrutinib or zanubrutinib), in patients with MCL who have never received any form of BTK inhibitor. This trial will look at how many people live with the disease without it getting worse. Like other cancer treatments, pirtobrutinib may affect both healthy cells and tumor cells, which can result in side effects that will also be looked at in this study. This study is active and currently recruiting new patients who have received at least one previous therapy for MCL and have never been treated with a BTK inhibitor. Clinical Trial Registration: NCT04662255 (ClinicalTrials.gov).


Assuntos
Antineoplásicos , Linfoma de Célula do Manto , Humanos , Adulto , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Antineoplásicos/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Ensaios Clínicos Fase III como Assunto
5.
J Clin Med ; 11(1)2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-35011768

RESUMO

Patients with myelodysplastic syndromes (MDS) often experience chronic anemia and long-term red blood cell transfusion dependence associated with significant burden on clinical and health-related quality of life (HRQoL) outcomes. In the MEDALIST trial (NCT02631070), luspatercept significantly reduced transfusion burden in patients with lower-risk MDS who had ring sideroblasts and were refractory to, intolerant to, or ineligible for prior treatment with erythropoiesis-stimulating agents. We evaluated the effect of luspatercept on HRQoL in patients enrolled in MEDALIST using the EORTC QLQ-C30 and the QOL-E questionnaire. Change in HRQoL was assessed every 6 weeks in patients receiving luspatercept with best supportive care (+ BSC) and placebo + BSC from baseline through week 25. No clinically meaningful within-group changes and between-group differences across all domains of the EORTC QLQ-C30 and QOL-E were observed. On one item of the QOL-E MDS-specific disturbances domain, patients treated with luspatercept reported marked improvements in their daily life owing to the reduced transfusion burden, relative to placebo. Taken together with previous reports of luspatercept + BSC reducing transfusion burden in patients from baseline through week 25 in MEDALIST, these results suggest luspatercept may offer a treatment option for patients that reduces transfusion burden while providing stability in HRQoL.

6.
Rev. bras. ciênc. mov ; 12(2): 19-24, 2004. graf
Artigo em Português | LILACS | ID: lil-524479

RESUMO

O processo de envelhecimento se associa ao desenvolvimento de várias doenças, que podem ser amenizadas pela prática de atividades físicas. Porém, quando essa atividade é realizada de forma inadequada, excedendo a capacidade do praticante, pode trazer riscos. Essa inadequação é principalmente observada quando a prática é feita sem orientação, o que muitas vezes ocorre em locais públicos. Este estudo objetivou descrever nos freqüentadores maiores de 60 anos do Parque Fernando Costa, o risco cardiovascular, a atividade física praticada e a condição física. Foram avaliadas 44 pessoas (67±5 anos), que responderam um questionário (doenças e fatores de risco cardiovascular e exercícios praticados) e tiveram dados antropométricos (peso e altura), cardiovasculares (pressão arterial), bioquímicos (glicemia e colesterol) e de condição física (condicionamento cardiovascular, força de membros superiores, inferiores e abdominal, e flexibilidade de ombros e lombar) medidos. Dos entrevistados, 14% eram cardiopatas e 34% apresentaram sintomas cardiovasculares. Além disso, 70% tinham pelo menos um fator de risco cardiovascular (52% hipertensão, 14% diabetes, 23% hipercolesterolemia, 16% obesidade e 9% sedentarismo). O número de pessoas ativas foi alto (91%), sendo a atividade mais praticada a aeróbia (92%), 3 a 5 vezes por semana (57%), 30 a 60 min (96%) e de intensidade moderada (75%). Quanto à capacidade física, os idosos apresentaram resultados dentro das médias esperadas para a idade. Em conclusão, o risco cardiovascular entre os idosos do parque encontra-se elevado, porém a prática de atividade física e a aptidão física foram adequadas para a faixa etária e para a manutenção da saúde cardiovascular.


Aging process is accompanied by the development of many diseases that can be prevented by physical exercise. However, inappropriate physical activities, that overcome subjects’ fitness, can increase cardiovascular risk. This condition is commonly observed when exercise is performed without previous orientation, which frequently occurs in public parks. Thus, the aim of the present study was to evaluate cardiovascular risk, physical activity, and physical fitness of subjects older than 60 years, who frequently went to Fernando Costa Park. Forty-four subjects (67±5 years) were evaluated by a questionnaire (cardiovascular disease and risk factors, and physical activity). Moreover, anthropometric (weight and height), cardiovascular (blood pressure), and biochemical data (glycemia and cholesterol), as well as physical fitness (cardiovascular performance, leg and arms strength, and lumbar and shoulder flexibility) were measured. Fourteen percent of the subjects presented cardiac disease, and 34% cardiac symptoms. Moreover, 70% of the subjects had at least one cardiovascular risk factor (52% hypertension, 14% diabetes, 23% hypercolesterolemia, 16% obesity, and 9% sedentary lifestyle). A lot of subjects practiced physical exercise (91%), and the most prevalent activity was the aerobic one (92%), done 3 to 5 times per week (57%), for 30 to 60 minutes (96%), and with moderate intensity (75%). In regard to physical fitness, subjects presented results similar to the ones expected for their age. In conclusion, the cardiovascular risk from elderly subjects that uses the park was high, however the physical activity, and fitness of these subjects were adequate for their age and to maintain them health.


Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso , Anormalidades Cardiovasculares , Áreas Verdes , Atividade Motora , Aptidão Física , Risco
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