Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
1.
Ann Oncol ; 26(5): 973-981, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25632070

RESUMO

BACKGROUND: A subgroup of sarcomas is characterized by defining chromosomal translocations, creating fusion transcription factor oncogenes. Resultant fusion oncoproteins associate with chromatin-modifying complexes containing histone deacetylases (HDAC), and lead to epigenetic transcriptional dysregulation. HDAC inhibitors were shown to be effective in vitro, reversing gene repression by these complexes, restoring PTEN expression and apoptosis via the PI3K/Akt/mTOR pathway. PATIENTS AND METHODS: SB939 is an oral inhibitor of classes 1 and 2 HDAC. Eligible patients with recurrent or metastatic translocation-associated sarcoma (TAS) by local pathology were treated with 60 mg/day every other day for 3 of 4 weeks. Central pathology review was conducted with fusion oncogenes characterized, and HDAC2 expression correlated with efficacy in pre-specified methods. RESULTS: Twenty-two patients were treated with a median of 2 cycles. Fourteen patients were assessable for response with confirmed specific chromosomal translocations; 8 had a best response of stable disease (SD) (median duration 5.4 months) with no confirmed objective responses. The 3-month progression-free survival (PFS) rate was 49%. Among those with HDAC2 score ≥5, 7/10 had SD, versus 0/3 with HDAC2 score <5. SB939 was considered as well tolerated with <10% patients experienced ≥grade 3 toxicity. CONCLUSION: This study was stopped prematurely due to prolonged unavailability of SB939. No objective responses were seen. Although the observed SD in HDAC2 high patients was interesting, due to the small sample size, no definitive conclusion can be drawn about the efficacy of SB939 in this patient population. CLINICAL TRIAL: NCT01112384.


Assuntos
Antineoplásicos/uso terapêutico , Benzimidazóis/uso terapêutico , Biomarcadores Tumorais/genética , Histona Desacetilase 2/antagonistas & inibidores , Inibidores de Histona Desacetilases/uso terapêutico , Recidiva Local de Neoplasia , Sarcoma/tratamento farmacológico , Translocação Genética , Administração Oral , Adulto , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/provisão & distribuição , Benzimidazóis/administração & dosagem , Benzimidazóis/efeitos adversos , Benzimidazóis/provisão & distribuição , Canadá , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Término Precoce de Ensaios Clínicos , Feminino , Histona Desacetilase 2/metabolismo , Inibidores de Histona Desacetilases/administração & dosagem , Inibidores de Histona Desacetilases/efeitos adversos , Inibidores de Histona Desacetilases/provisão & distribuição , Humanos , Masculino , Pessoa de Meia-Idade , Sarcoma/enzimologia , Sarcoma/secundário , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
2.
Br J Cancer ; 105(7): 938-44, 2011 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-21878940

RESUMO

BACKGROUND: To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacokinetics (PK) and pharmacodynamics (PD) of higher doses of erlotinib. METHODS: Patients initially received erlotinib 150 mg per day. The dose was successively increased in each patient to that associated with a TR. Anticancer activity was evaluated. Plasma, skin, and hair were sampled for PK and PD studies. RESULTS: Erlotinib dose escalation to 200-475 mg per day was feasible in 38 (90%) of 42 patients. Twenty-four (57%) patients developed a TR, but 19 (79%) did so at 150 mg per day. Five (12%) patients, all of whom developed a TR, had a partial response. Median progression-free survival (PFS) was 2.3 months (95% CI: 1.61, 4.14); median PFS was 3.5 months and 1.9 months, respectively, for patients who did and did not experience a TR (hazard ratio, 0.51; P=0.051). Neither rash severity nor response correlated with erlotinib exposure. CONCLUSION: Intrapatient dose escalation of erlotinib does not appreciably increase the propensity to experience a maximal level of tolerable skin toxicity, or appear to increase the anticancer activity of erlotinib in NSCLC.


Assuntos
Adenocarcinoma/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Exantema/induzido quimicamente , Neoplasias Pulmonares/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Quinazolinas/uso terapêutico , Adenocarcinoma/patologia , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/patologia , Cloridrato de Erlotinib , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Inibidores de Proteínas Quinases/farmacocinética , Quinazolinas/farmacocinética , Distribuição Tecidual
3.
Eur J Clin Nutr ; 70(11): 1230-1238, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27273068

RESUMO

Great discrepancies exist in the reported prevalence of altered energy metabolism (hypo- or hypermetabolism) in cancer patients, which is likely due to the vast array of phenomena that can affect energy expenditure in these patients. The purpose of this review was to critically evaluate key determinants of energy expenditure in cancer and the relevance for clinical practice. Resting energy expenditure (REE) is the largest and most commonly measured component of total energy expenditure. In addition to the energetic demand of the tumor itself, REE may be increased due to changes in inflammation, body composition and brown adipose tissue activation. Energy expenditure from physical activity is often lower in cancer compared with healthy populations, and there is evidence to suggest that the thermic effect of food might also be blunted and affected by cancer therapy. Although accurate assessment of energy metabolism is a cornerstone of adequate nutritional therapy, prediction methods often do not capture the true energy expenditure of most cancer patients. In fact, limits of agreement of prediction equations may range from 40% below to 30% above measured REE. Such variability highlights the need for a more comprehensive understanding of energy expenditure in cancer and the value of accurately assessing the energy needs of these patients.


Assuntos
Metabolismo Energético , Neoplasias , Necessidades Nutricionais , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA