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2.
Artigo em Inglês | MEDLINE | ID: mdl-30175393

RESUMO

PURPOSE: Advanced pancreatic adenocarcinoma (PA) is an aggressive disease that has poor prognosis and frequently interferes with patient's quality of life. There has been progress in first-line regimens; however, there is no standard second-line regimen. The aim of this study is to analyze second-line gemcitabine after first-line fluorouracil (FU) + leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX) regimen. METHODS: This study included consecutive patients with advanced PA treated at Hospital Sirio-Libanês from 2011 to 2016. The patients received FOLFIRINOX as first-line treatment and upon progression, received gemcitabine alone. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 54 patients were evaluated. Most patients were male (61.1%) and most had an ECOG performance status of 0 or 1 prior to the beginning of second-line treatment (66.6%). The mean number of gemcitabine cycles was 3.4. Most patients had disease progression as the best response to treatment (75.9%), 11.1% had stable disease, and 9.3% experienced a partial response. The median progression-free survival was 1.7 months, and the median overall survival was 6.8 months. CONCLUSIONS: Gemcitabine alone did not show meaningful clinical benefit as second-line treatment after FOLFIRINOX.

3.
BMC Cancer ; 18(1): 887, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30208863

RESUMO

BACKGROUND: Ameloblastoma is a slow-growing neoplasm of the jaw, for which the standard treatment is surgical removal of the lesion with high recurrence rates and elevated morbidity. Systemic therapy is not established in the literature. CASE PRESENTATION: We present a case of a 29-year-old woman diagnosed with an ameloblastoma of the left mandible who had been subjected to several surgical procedures over twenty years due to multiple local recurrences. Molecular testing revealed a BRAF V600E mutation, and vemurafenib was started. She experienced complete resolution of symptoms related to the disease, and image scans evidenced continuous shrinkage of the neoplastic lesion after eleven months of therapy. CONCLUSION: This is the first report showing clinical benefit and radiological response with vemrafenib for recurrent ameloblastoma. Targeted therapy addressing BRAF V600E mutation has the potential to change clinical practice of this rare disease.

4.
Rev. Assoc. Med. Bras. (1992) ; 63(9): 814-823, 2017. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-896397

RESUMO

Summary Following decades of relative ostracism, advances in the treatment of melanoma have brought a new reality for patients, physicians and researchers. While antibodies targeting molecules involved in the modulation of the interaction between melanoma and immune cells changed the meaning of the term "cancer immunotherapy," a better characterization of the molecular aberrations involved in melanoma carcinogenesis prompted the development of inhibitors of the mitogen-activated protein kinase pathway (MAPK) that also led to significant improvements both in response rates and survival. As a result, new drugs have been approved for clinical use in the United States and Europe, including the immune-checkpoint blockers ipilmumab, pembrolizumab and nivolumab, the oncolytic herpesvirus talimogene laherparepvec, and the targeted-agents vemurafenib, dabrafenib, cobimetinib and trametinib. In this article, we review the results of studies that brought new approaches to the bedside and discuss how these developments are being incorporated into the care of patients in Brazil.


Resumo Após décadas de ostracismo, os recentes avanços no tratamento do melanoma trouxeram uma nova realidade para pacientes, médicos e pesquisadores. Enquanto anticorpos monoclonais voltados a moléculas envolvidas na modulação da interação entre células do melanoma e do sistema imune consolidaram o uso da "imunoterapia", um melhor conhecimento acerca das aberrações genômicas envolvidas na carcinogênese do melanoma viabilizaram o desenvolvimento de inibidores da via mitogen-activated protein kinase pathway (MAPK), o que também resultou em ganhos significativos em taxas de resposta e sobrevida. Consequentemente, novas modalidades de tratamento foram aprovadas para uso clínico nos Estados Unidos e na Europa, incluindo os bloqueadores de correceptores imunes ipilimumabe, nivolumabe e pembrolizumabe, o herpesvírus oncolítico talimogene laherparepvec (T-VEC), e os agentes-alvo vemurafenibe, dabrafenibe, cobimetinibe e trametinibe. Nesse artigo, revisamos os resultados que trouxeram novas alternativas para a prática clínica e discutimos a incorporação desses avanços ao cuidado de pacientes no Brasil.

5.
Rev Assoc Med Bras (1992) ; 63(9): 814-823, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29239458

RESUMO

Following decades of relative ostracism, advances in the treatment of melanoma have brought a new reality for patients, physicians and researchers. While antibodies targeting molecules involved in the modulation of the interaction between melanoma and immune cells changed the meaning of the term "cancer immunotherapy," a better characterization of the molecular aberrations involved in melanoma carcinogenesis prompted the development of inhibitors of the mitogen-activated protein kinase pathway (MAPK) that also led to significant improvements both in response rates and survival. As a result, new drugs have been approved for clinical use in the United States and Europe, including the immune-checkpoint blockers ipilmumab, pembrolizumab and nivolumab, the oncolytic herpesvirus talimogene laherparepvec, and the targeted-agents vemurafenib, dabrafenib, cobimetinib and trametinib. In this article, we review the results of studies that brought new approaches to the bedside and discuss how these developments are being incorporated into the care of patients in Brazil.


Assuntos
Antineoplásicos/administração & dosagem , Imunoterapia/métodos , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Humanos , Proteínas Proto-Oncogênicas B-raf/administração & dosagem
6.
Clinics (Sao Paulo) ; 72(10): 588-594, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29160420

RESUMO

OBJECTIVES: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer. METHODS: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy. RESULTS: From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months. CONCLUSION: We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.


Assuntos
Genômica/métodos , Terapia de Alvo Molecular/métodos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Análise de Sequência de DNA/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Intervalo Livre de Doença , Feminino , Genômica/tendências , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias/mortalidade , Neoplasias/patologia , Medicina de Precisão/métodos , Receptor ErbB-2/antagonistas & inibidores , Reprodutibilidade dos Testes , Análise de Sequência de DNA/tendências , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
7.
Clinics ; 72(10): 588-594, Oct. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-890681

RESUMO

OBJECTIVES: With the development of next-generation sequencing (NGS) technologies, DNA sequencing has been increasingly utilized in clinical practice. Our goal was to investigate the impact of genomic evaluation on treatment decisions for heavily pretreated patients with metastatic cancer. METHODS: We analyzed metastatic cancer patients from a single institution whose cancers had progressed after all available standard-of-care therapies and whose tumors underwent next-generation sequencing analysis. We determined the percentage of patients who received any therapy directed by the test, and its efficacy. RESULTS: From July 2013 to December 2015, 185 consecutive patients were tested using a commercially available next-generation sequencing-based test, and 157 patients were eligible. Sixty-six patients (42.0%) were female, and 91 (58.0%) were male. The mean age at diagnosis was 52.2 years, and the mean number of pre-test lines of systemic treatment was 2.7. One hundred and seventy-seven patients (95.6%) had at least one identified gene alteration. Twenty-four patients (15.2%) underwent systemic treatment directed by the test result. Of these, one patient had a complete response, four (16.7%) had partial responses, two (8.3%) had stable disease, and 17 (70.8%) had disease progression as the best result. The median progression-free survival time with matched therapy was 1.6 months, and the median overall survival was 10 months. CONCLUSION: We identified a high prevalence of gene alterations using an next-generation sequencing test. Although some benefit was associated with the matched therapy, most of the patients had disease progression as the best response, indicating the limited biological potential and unclear clinical relevance of this practice.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adulto Jovem , Genômica/métodos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Análise de Sequência de DNA/métodos , Progressão da Doença , Intervalo Livre de Doença , Genômica/tendências , Estimativa de Kaplan-Meier , Terapia de Alvo Molecular/métodos , Metástase Neoplásica , Neoplasias/mortalidade , Neoplasias/patologia , Medicina de Precisão/métodos , Receptor ErbB-2/antagonistas & inibidores , Reprodutibilidade dos Testes , Análise de Sequência de DNA/tendências , Fatores de Tempo , Resultado do Tratamento
9.
J. bras. med ; 83(4): 18-24, out. 2002. tab, graf
Artigo em Português | LILACS | ID: lil-335291

RESUMO

Os ácaros são considerados a maior fonte de alérgenos inalantes envolvidos em doenças alérgicas respiratórias. Com o objetivo de correlacionar os ácaros mais prevalentes na poeira domiciliar aos agentes etiológicos mais comuns da população atópica, realizamos um estudo randomizado, prospectivo e pioneiro no município de Bragança Paulista, entre abril de 1998 e setembro de 1999. Nas amostras de poeira encontramos as espécies D. pteronyssinus (55,36 por cento), família Tarsonemidae (16,96 por cento) e B. tropicalis (12,80 por cento). Dos 90 voluntários testados com o prick teste encontramos 71 por cento de positividade aos alérgenos poeira doméstica (60 por cento), D. pteronyssinus (56,70 por cento) e B. tropicalis (51,10 por cento). A família Tarsonemidae assume um lugar de destaque entre as espécies encontradas, fato incomum na bibliografia pesquisada


Assuntos
Humanos , Ácaros/classificação , Ácaros/patogenicidade , Alérgenos/toxicidade , Poeira , Poluentes Atmosféricos , Doenças Respiratórias/etiologia
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