Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.724
Filtrar
3.
N Engl J Med ; 385(8): 683-694, 2021 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-34407342

RESUMO

BACKGROUND: Patients with renal-cell carcinoma who undergo nephrectomy have no options for adjuvant therapy to reduce the risk of recurrence that have high levels of supporting evidence. METHODS: In a double-blind, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with clear-cell renal-cell carcinoma who were at high risk for recurrence after nephrectomy, with or without metastasectomy, to receive either adjuvant pembrolizumab (at a dose of 200 mg) or placebo intravenously once every 3 weeks for up to 17 cycles (approximately 1 year). The primary end point was disease-free survival according to the investigator's assessment. Overall survival was a key secondary end point. Safety was a secondary end point. RESULTS: A total of 496 patients were randomly assigned to receive pembrolizumab, and 498 to receive placebo. At the prespecified interim analysis, the median time from randomization to the data-cutoff date was 24.1 months. Pembrolizumab therapy was associated with significantly longer disease-free survival than placebo (disease-free survival at 24 months, 77.3% vs. 68.1%; hazard ratio for recurrence or death, 0.68; 95% confidence interval [CI], 0.53 to 0.87; P = 0.002 [two-sided]). The estimated percentage of patients who remained alive at 24 months was 96.6% in the pembrolizumab group and 93.5% in the placebo group (hazard ratio for death, 0.54; 95% CI, 0.30 to 0.96). Grade 3 or higher adverse events of any cause occurred in 32.4% of the patients who received pembrolizumab and in 17.7% of those who received placebo. No deaths related to pembrolizumab therapy occurred. CONCLUSIONS: Pembrolizumab treatment led to a significant improvement in disease-free survival as compared with placebo after surgery among patients with kidney cancer who were at high risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck; KEYNOTE-564 ClinicalTrials.gov number, NCT03142334.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nefrectomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Método Duplo-Cego , Feminino , Humanos , Análise de Intenção de Tratamento , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva , Análise de Sobrevida
4.
Front Immunol ; 12: 711915, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276706

RESUMO

Passive antibody therapy has been used to treat outbreaks of viral disease, including the ongoing pandemic of severe respiratory acute respiratory syndrome (SARS) coronavirus 2 (SARS-CoV-2) or COVID-19. However, the real benefits of the procedure are unclear. We infused a concentrated solution of neutralizing anti-SARS-CoV-2 antibodies obtained from a convalescent donor with a single session of double filtration plasmapheresis (DFPP) into a 56-year-old woman with long history of unremitting, severe COVID-19. She was unable to establish an adequate antiviral immune response because of previous chemotherapy, including the infusion of the anti-CD20 monoclonal antibody rituximab, administered to treat a diffuse large B-cell lymphoma. The disease promptly recovered despite evidence of no endogenous anti-SARS-CoV-2 antibody production. The observation that passive antibody therapy might prove particularly effective in immunodepressed COVID-19 patients requires evaluation in prospective randomized controlled trial.


Assuntos
Anticorpos Neutralizantes/uso terapêutico , Anticorpos Antivirais/uso terapêutico , COVID-19/terapia , Imunização Passiva/métodos , Hospedeiro Imunocomprometido , Imunoglobulina G/uso terapêutico , Plasmaferese/métodos , SARS-CoV-2/genética , Antineoplásicos Imunológicos/efeitos adversos , Antivirais/uso terapêutico , COVID-19/imunologia , COVID-19/virologia , Feminino , Humanos , Imunidade/efeitos dos fármacos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , RNA Viral/genética , Rituximab/efeitos adversos , Resultado do Tratamento
5.
Ann Hematol ; 100(9): 2155-2172, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34318356

RESUMO

Multiple myeloma (MM) remains an incurable disease with the majority of patients experiencing disease relapse despite response to initial therapy. Antibody-drug conjugates (ADCs) and bispecific T-cell engagers are innovative immunotherapeutic approaches currently in development for the treatment of MM. This systematic review summarizes the efficacy and safety of ADCs and bispecific T-cell engagers in relapsed refractory (RR) MM patients from 2010 to date. Comprehensive literature search was conducted on PubMed, EMBASE, Wiley Cochrane Library, Web of Science, and Clinicaltrials.gov . A total of 13 studies (n = 529) met inclusion eligibility. All studies were prospective in nature investigating ADCs or bispecific T-cell engagers in RR MM; 10 trials were phase 1 and 3 were phase 2. The median age of patients ranged from 24 to 82 years. Among trials with ADC regimens, the overall response (OR) ranged from 34 to 60% and complete response (CR) ranged from 3 to 6%. The most common non-hematologic adverse event (AE) of ADCs was keratopathy, while anemia and thrombocytopenia were the most common hematological AEs. With bispecific T-cell engagers , ORR ranged from 31 to 83%, CR ranged from 7 to 22%, and partial response (PR) ranged from 5 to 16%. The most common non-hematologic AE of bispecific T-cell engagers was cytokine release syndrome (CRS) while the most common hematological AE was neutropenia. Initial data appears to show good clinical activity and tolerable safety profiles, making ADCs and bispecific T-cell engagers promising agents for RRMM. Future studies with newer combinations and a longer follow-up are needed to determine the precise role of these novel therapies in the evolving paradigm of MM treatment.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Imunoconjugados/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Animais , Anticorpos Biespecíficos/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Humanos , Imunoconjugados/efeitos adversos , Recidiva Local de Neoplasia/tratamento farmacológico
6.
Adv Ther ; 38(8): 4581-4591, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34241781

RESUMO

INTRODUCTION: Patients with advanced cutaneous squamous cell carcinoma (CSCC) have a poor prognosis. Blocking the PD-1-PD-L1 axis has shown promising activity in this patient population. We assessed the safety and antitumor activity of PD-1 inhibitor pembrolizumab in patients with refractory advanced CSCC. METHODS: This was a prespecified subgroup analysis of patients with advanced CSCC who enrolled in an open-label, phase II clinical trial for pembrolizumab in patients with refractory rare cancers during 2016-2018. Patients received pembrolizumab 200 mg intravenously every 21 days until progressive disease, unacceptable adverse event, or completion of 24 months of treatment. The primary endpoint was nonprogression rate (NPR) at 27 weeks; secondary endpoints included safety, objective response rate (ORR) per irRECIST, clinical benefit rate (CBR), progression-free survival, and overall survival. RESULTS: Twenty patients with refractory CSCC enrolled; 19 were evaluable for efficacy. Median follow-up time was 44.1 months. The NPR at 27 weeks was 37% (95% CI 0.16-0.62). Three patients had a complete response (CR), three had a partial response, and one had stable disease, for an ORR of 32% and a CBR of 37%; median duration of response was 27.3 months. All three patients with a CR remained free of recurrence at the time of writing. Severe treatment-related adverse events (grade ≥ 3) occurred in 10% of patients (2/20). PD-L1 expression was not correlated with response to pembrolizumab. CONCLUSION: A long-term follow-up confirms pembrolizumab's antitumor activity and safety profile in patients with refractory CSCC. Patients with a CR may experience cure. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02721732, Registered March 29, 2016.


Assuntos
Antineoplásicos Imunológicos , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico
8.
Lancet Haematol ; 8(8): e593-e604, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34329579

RESUMO

Progressive multifocal leukoencephalopathy (PML) is a serious and usually fatal CNS infection caused by the John Cunningham virus. CD4+ and CD8+ T-cell lymphopenia, resulting from HIV infection, chemotherapy, or immunosuppressive therapy, are primary risk factors for PML. Following its introduction in 1997, the immunomodulatory anti-CD20 monoclonal antibody, rituximab, has received regulatory approval worldwide for treatment of non-Hodgkin lymphoma, rheumatoid arthritis, chronic lymphocytic leukaemia, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulagris. Rituximab leads to prolonged B-lymphocyte depletion, potentially allowing John Cunningham viral infection to occur. Six unexpected cases of PML infection developing in rituximab-treated patients were first reported in 2002. We review 20 years of information on clinical findings, pathology, epidemiology, proposed pathogenesis, and risk-management issues associated with PML infection developing after rituximab treatment. Since the first case series report of 52 cases of rituximab-associated PML among patients with non-Hodgkin lymphoma or chronic lymphocytic leukaemia in 2009, updated and diligent pharmacovigilance efforts have provided reassurance that this fatal toxicity is a rare clinical event with concurring causal factors. International harmonisation of safety warnings around rituximab-associated PML should be considered, with these notifications listing rituximab-associated PML under a section titled warnings and precautions as is the case in most countries, rather than a boxed warning as is the case in the USA.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Leucoencefalopatia Multifocal Progressiva/patologia , Neoplasias/tratamento farmacológico , Rituximab/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Humanos , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Prognóstico
9.
Anticancer Res ; 41(8): 3899-3904, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34281852

RESUMO

BACKGROUND/AIM: This phase II trial evaluated the efficacy and safety of neoadjuvant nab-paclitaxel plus cyclophosphamide (CPA) plus trastuzumab (AbraC-HER) in patients with early HER2-positive breast cancer. PATIENTS AND METHODS: This was a single-arm, open-label, single-center prospective phase II study. The primary endpoint was pathological complete response rate (pCR rate). The secondary endpoints were clinical antitumor efficacy and the frequency and severity of adverse events. RESULTS: Fifty-nine patients were enrolled in this study. pCR (ypT0/is ypN0) was achieved in 29 patients (49%). The overall response rate was 88.1% (52/59) in all patients. Dose reductions because of adverse events occurred in 3 patients (5.1%) and relative dose intensity was 98%. Compared to Abra-HER, AbraC-HER induced fewer adverse effects. CONCLUSION: Treatment with nab-paclitaxel plus CPA plus trastuzumab was tolerable and effective with a high pCR rate. This AbraC-HER neoadjuvant therapy may be a feasible new treatment option for patients with early HER2-positive breast cancer.


Assuntos
Albuminas/uso terapêutico , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Paclitaxel/uso terapêutico , Trastuzumab/uso terapêutico , Adulto , Idoso , Albuminas/efeitos adversos , Antineoplásicos Alquilantes/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/mortalidade , Ciclofosfamida/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Terapia Neoadjuvante , Paclitaxel/efeitos adversos , Receptor ErbB-2 , Trastuzumab/efeitos adversos
10.
Int J Mol Sci ; 22(12)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200673

RESUMO

Pembrolizumab (mAb to PD-1) has been recently approved for the therapy of pretreated urothelial cancer. Despite the efficacy, it is often accompanied by unpredictable and sometime severe immune-related (ir) adverse events (AEs). Here, we report the clinical and immune-biological characterization of a patient with a metastatic bladder cancer who developed myositis signs (M) and a myasthenia-like syndrome (MLS) during treatment with pembrolizumab. The patient presented an autoimmunity-associated HLA haplotype (HLA-A*02/HLA-B*08/HLA-C*07/HLA-DRB1*03) and experienced an increase in activated CD8 T-cells along the treatment. The symptomatology regressed after pembrolizumab discontinuation and a pyridostigmine and steroids-based therapy. This is the first report of concurrent M and MLS appearance in cancer patients receiving pembrolizumab. More efforts are needed to define early the risk and the clinical meaning of irAEs in this setting.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Autoimunidade , Antígenos HLA/imunologia , Miastenia Gravis/patologia , Miosite/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Idoso , Humanos , Masculino , Miastenia Gravis/induzido quimicamente , Miastenia Gravis/imunologia , Miosite/induzido quimicamente , Miosite/imunologia , Prognóstico
11.
Intern Med J ; 51(7): 1016-1020, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34278695

RESUMO

Immune checkpoint inhibitors are increasingly being utilised as an effective therapy for a variety of cancers. However, they have the potential to cause serious autoimmune toxicities in multiple organ systems termed 'immunotherapy-related adverse events'. Endocrine toxicities are common, can occur well after commencement of therapy and can result in significant morbidity and mortality if not recognised. This makes it important for all physicians, in addition to endocrinologists and oncologists, to understand the nature of these reactions and the general approach to their diagnosis and management. This review aims to provide an overview of the epidemiology, pathophysiology, clinical presentation and management of the endocrine adverse events.


Assuntos
Antineoplásicos Imunológicos , Sistema Endócrino/efeitos dos fármacos , Inibidores de Checkpoint Imunológico , Neoplasias , Antineoplásicos Imunológicos/efeitos adversos , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias/tratamento farmacológico
12.
Med Clin North Am ; 105(4): 737-755, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34059248

RESUMO

The cutaneous lymphomas are malignancies of T-cell and B-cell lymphocytes in which the skin is the primary organ of involvement. The cutaneous T-cell lymphomas include variants that can mimic the presentation of common skin diseases or arthropod bites. Mycosis fungoides, the most common cutaneous T-cell lymphoma, usually presents as fixed asymptomatic patches or plaques in sun-protected areas. The cutaneous B-cell lymphomas have fewer variants that often present as papules or nodules that can mimic nonmelanoma skin cancers. Some therapies for cutaneous lymphoma have unique side effects such as central hypothyroidism, hyperlipidemia, and peripheral neuropathy.


Assuntos
Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/terapia , Dermatopatias/diagnóstico , Neoplasias Cutâneas/patologia , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Artrópodes , Bexaroteno/efeitos adversos , Mordeduras e Picadas/diagnóstico , Brentuximab Vedotin/efeitos adversos , Diagnóstico Diferencial , Humanos , Hiperlipidemias/induzido quimicamente , Hipotireoidismo/induzido quimicamente , Linfoma Anaplásico Cutâneo Primário de Células Grandes/diagnóstico , Linfoma Cutâneo de Células T/classificação , Papulose Linfomatoide/diagnóstico , Micose Fungoide/diagnóstico , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Prognóstico , Síndrome de Sézary/diagnóstico , Dermatopatias/patologia
15.
Medicine (Baltimore) ; 100(19): e25773, 2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34106609

RESUMO

RATIONALE: Anti-PD-1 antibody is the standard therapy for treatment-resistant gastric cancer, but only a limited number of patients respond. Additionally, cases of hyper-progressive disease (HPD) in which tumor growth accelerates after anti-PD-1 antibody administration have been reported; however, the biological mechanism has not been elucidated. PATIENT CONCERNS: In the present case, metastatic gastric cancer was treated with the anti-PD-1 antibody, nivolumab, as third-line treatment. DIAGNOSIS: After the initiation of nivolumab therapy, a rapidly enlarging para-aortic lymph nodes were observed leading to the diagnosis of HPD. INTERVENTIONS: Multiplex immunohistochemistry was used to examine immune cells infiltrating in the primary tumor and in liver metastasis which were obtained before nivolumab treatment, and in lymph node metastasis which presented with HPD after nivolumab therapy. OUTCOMES: In the primary tumor, helper T (Th) cells, cytotoxic T lymphocytes (CTLs), regulatory T (Treg) cells, and PD-L1-negative macrophages were observed. On the other hand, in metastatic lymph nodes presenting with HPD, PD-L1-positive macrophages prominently increased, while Treg cells, CTLs, and Th cells decreased. PD-L1 expression was not observed in gastric cancer cells among the three specimens. LESSONS: The findings suggest the possibility that PD-L1-positive M2 macrophage might contribute to acceleration of tumor growth with anti-PD-1 therapy in the present case.


Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos Imunológicos/efeitos adversos , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Macrófagos Associados a Tumor/efeitos dos fármacos , Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Biomarcadores Tumorais/antagonistas & inibidores , Progressão da Doença , Evolução Fatal , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Nivolumabe/uso terapêutico , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/patologia , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia
16.
Am J Clin Oncol ; 44(7): 340-349, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34151896

RESUMO

OBJECTIVE: Ado-trastuzumab emtansine (T-DM1) was recently approved for patients with human epidermal growth factor receptor 2 positive (HER2+) early breast cancer (eBC) with residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment. Cost-effectiveness analysis was conducted to compare T-DM1 versus trastuzumab in the United States. MATERIALS AND METHODS: A Markov cohort-based model tracked clinical and economic outcomes over a lifetime horizon from a US payer perspective. The model included 6 health states: invasive disease-free, nonmetastatic (locoregional) recurrence, remission, first-line and second-line metastatic BC and death. Model state transitions were based on statistical extrapolation of the head-to-head KATHERINE study and published sources. Dosing and treatment duration reflected prescribing information and trials. Costs (2019 US dollars) associated with pharmaceutical treatment (wholesale acquisition costs), health state specific care, adverse events, and end-of-life care were included. Health state utilities were obtained from KATHERINE and published literature. RESULTS: T-DM1 dominated trastuzumab, yielding lower lifetime costs (-$40,271), and higher life-years (2.980) and quality-adjusted life-years (2.336). Results were driven by patients receiving T-DM1 spending less time in more costly downstream health states, as these patients are less likely to experience a recurrence overall, despite having a higher likelihood of metastatic disease (distant recurrence) in the subset of patients who experience recurrence. Probabilistic sensitivity analysis indicated robust results, with 96.7% of 5000 stochastic simulations producing dominance for T-DM1. The most influential variables were related to treatment costs, off treatment utilities, and health state costs. Additional scenario analyses tested a range of model inputs and assumptions, and produced consistent results. CONCLUSION: Relative to trastuzumab, T-DM1 treatment for patients with HER2+ eBC who have residual invasive disease after neoadjuvant taxane and trastuzumab-based treatment is likely to reduce the overall financial burden of cancer, while simultaneously improving patient outcomes.


Assuntos
Ado-Trastuzumab Emtansina/economia , Ado-Trastuzumab Emtansina/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante/economia , Ado-Trastuzumab Emtansina/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/economia , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias da Mama/economia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Análise Custo-Benefício , Custos de Medicamentos , Feminino , Humanos , Recidiva Local de Neoplasia , Qualidade de Vida , Trastuzumab/efeitos adversos , Trastuzumab/economia , Trastuzumab/uso terapêutico , Estados Unidos
17.
J Hematol Oncol ; 14(1): 88, 2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090506

RESUMO

Antibody-drug conjugates (ADCs) are a promising class of immunotherapies with the potential to specifically target tumor cells and ameliorate the therapeutic index of cytotoxic drugs. ADCs comprise monoclonal antibodies, cytotoxic payloads with inherent antitumor activity, and specialized linkers connecting the two. In recent years, three ADCs, brentuximab vedotin, polatuzumab vedotin, and loncastuximab tesirine, have been approved and are already establishing their place in lymphoma treatment. As the efficacy and safety of ADCs have moved in synchrony with advances in their design, a plethora of novel ADCs have garnered growing interest as treatments. In this review, we provide an overview of the essential elements of ADC strategies in lymphoma and elucidate the up-to-date progress, current challenges, and novel targets of ADCs in this rapidly evolving field.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Imunoconjugados/uso terapêutico , Linfoma/tratamento farmacológico , Animais , Antineoplásicos Imunológicos/efeitos adversos , Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos , Humanos , Imunoconjugados/efeitos adversos
18.
Radiol Med ; 126(9): 1249-1254, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34081269

RESUMO

BACKGROUND: High-grade gliomas are among the most aggressive central nervous system primary tumors, with a high risk of recurrence and a poor prognosis. Re-operation, re-irradiation, chemotherapy are options in this setting. No-best therapy has been established. Bevacizumab was approved on the basis of two Phase 2 trials that evaluated its efficacy in patients with recurrent glioblastoma. MATERIALS AND METHODS: We have retrospectively review data of patients with high-grade glioma treated at our institution that undergone radiological or histological progression after at least one systemic treatment for recurrent disease. Bevacizumab was administered alone or in combination with chemotherapy until disease progression or unacceptable toxicity. Bevacizumab regimen was analyzed to assess PFS and OS. Histological, molecular and clinical features of the entire cohort were collected. RESULTS: We reviewed data from 92 patients, treated from April 2009 to November 2019, with histologically confirmed diagnosis of high-grade gliomas and recurrent disease. A PFS of 55.2%, 22.9% and 9.6% was observed at 6, 12 and 24 months, respectively. Performance status, age at diagnosis (< 65 or > 65 ys.) and use of corticosteroids during bevacizumab therapy were strongly associated with PFS. The OS was 74.9% at 6 months, 31.7% at 12 months, 10.1% at 24 months. In our cohort, 51.1% were long-term responders (PFS > 6 months). Globally, bevacizumab treatment was well tolerated. CONCLUSION: Our analysis confirms the efficacy of bevacizumab in recurrent high-grade glioma patients with an acceptable toxicity profile, in keeping with its known safety in the literature.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Glioma/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/mortalidade , Glioblastoma/patologia , Glioma/mortalidade , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Análise de Sobrevida
19.
In Vivo ; 35(4): 2321-2326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34182512

RESUMO

BACKGROUND: The development of immune-related adverse events (irAEs) has been found to be associated with survival benefits in some cancers. However, data on the relation between irAEs and gastroesophageal adenocarcinoma (GEA) or esophageal squamous cell carcinoma (ESCC) are scarce. PATIENTS AND METHODS: We retrospectively reviewed the data of 29 GEA and 21 ESCC patients treated with nivolumab. We investigated the impact of the development of irAEs in GEA and ESCC patients on best overall response and survival. RESULTS: Patients with irAEs had significantly better best overall response, overall survival and progression-free survival than those without irAEs (p=0.007, p<0.001 and p=0.005, respectively). Multivariate analyses identified an Eastern Cooperative Oncology Group performance status ≥2 and the absence of an irAE as independent poor prognostic factors (p<0.001 and 0.016, respectively). CONCLUSION: The development of irAEs has the potential to predict survival outcomes in patients with GEA and ESCC treated with nivolumab.


Assuntos
Antineoplásicos Imunológicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Neoplasias Pulmonares , Antineoplásicos Imunológicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/efeitos adversos , Estudos Retrospectivos
20.
Am J Case Rep ; 22: e931702, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34185763

RESUMO

BACKGROUND Immune checkpoint inhibitors (ICIs) are a novel class of antibodies, which have been increasingly utilized in cancer immunotherapies. Pembrolizumab is a humanized IgG4 monoclonal antibody, which acts against programmed cell death (PD)-1 receptors to help restore the body's T-cell and immune response. CASE REPORT In this case, we present a 51-year-old woman with a past medical history of lung adenocarcinoma and triple-positive breast cancer who was actively receiving therapy with pembrolizumab. Following her second chemotherapy cycle, she developed a severe case of diabetic ketoacidosis (DKA), with concern for new-onset autoimmune type 1 diabetes mellitus (T1DM), secondary to her recent ICI therapy. The patient was initiated on a high-dose insulin infusion for rapid glycemic control and was successfully transitioned to a subcutaneous regimen approximately 24 h after presentation. She additionally developed other autoimmune-related complications, including hepatoxicity, duodenitis, and a maculopapular rash, which all resolved upon discontinuation of the ICI treatment. Her laboratory test results were consistent with positive anti-glutamic acid decarboxylase (anti-GAD) antibodies and undetectable c-peptides, illustrating the uniqueness of an ICI potentially precipitating an autoimmune T1DM. CONCLUSIONS Immune-related adverse events from ICI therapy warrant further investigation to acknowledge the risk of potentially life-threatening adverse reactions, such as the development of DKA. Patients receiving ICI therapy should be educated on signs and symptoms of hyperglycemia, and routine measurements of blood glucose levels should be completed during each chemotherapy cycle. Future research in assessing potential biomarkers of beta cell dysfunction, such as anti-GAD antibodies and c-peptides, is of interest, particularly for patients receiving ICI therapies.


Assuntos
Antineoplásicos Imunológicos , Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/efeitos adversos , Cetoacidose Diabética/induzido quimicamente , Feminino , Humanos , Imunoterapia/efeitos adversos , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...