RESUMO
Treatment with azacitidine (AZA), a demethylating agent, prolonged overall survival (OS) vs conventional care in patients with higher-risk myelodysplastic syndromes (MDS). As median survival with monotherapy is <2 years, novel agents are needed to improve outcomes. This phase 1b/2b trial (n=113) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of panobinostat (PAN)+AZA (phase 1b) and evaluate the early efficacy and safety of PAN+AZA vs AZA monotherapy (phase 2b) in patients with higher-risk MDS, chronic myelomonocytic leukemia or oligoblastic acute myeloid leukemia with <30% blasts. The MTD was not reached; the RP2D was PAN 30 mg plus AZA 75 mg/m2. More patients receiving PAN+AZA achieved a composite complete response ([CR)+morphologic CR with incomplete blood count+bone marrow CR (27.5% (95% CI, 14.6-43.9%)) vs AZA (14.3% (5.4-28.5%)). However, no significant difference was observed in the 1-year OS rate (PAN+AZA, 60% (50-80%); AZA, 70% (50-80%)) or time to progression (PAN+AZA, 70% (40-90%); AZA, 70% (40-80%)). More grade 3/4 adverse events (97.4 vs 81.0%) and on-treatment deaths (13.2 vs 4.8%) occurred with PAN+AZA. Further dose or schedule optimization may improve the risk/benefit profile of this regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Leucemia Mielomonocítica Crônica/tratamento farmacológico , Leucemia Mielomonocítica Crônica/patologia , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/patologia , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Azacitidina/administração & dosagem , Medula Óssea/patologia , Feminino , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Indóis/administração & dosagem , Estimativa de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidade , Leucemia Mielomonocítica Crônica/mortalidade , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Panobinostat , Resultado do TratamentoRESUMO
AIM: Quality of life (QOL) was assessed after palliative surgery for incurable metastatic colorectal cancer (CRC). METHOD: Newly diagnosed patients with incurable metastatic CRC who were offered elective palliative surgical intervention were included. The European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR29 questionnaire was used for the assessment of QOL at baseline and at 3 and 6 months after surgery. Generalized estimating equations were used to estimate the mean change in the QOL score from baseline. RESULTS: Twenty-four patients formed the study group. Sixteen underwent resection of the primary tumour and eight had a proximal diversion or bypass. The Global Health (GH) score and Social Functioning (SF) score improved at 3 and 6 months after intervention respectively (GH +11, P = 0.021; SF +15, P = 0.005). Mean anxiety scores were markedly improved from the baseline of 51 to 71 (P = 0.004, 3 months) and 76 (P = 0.002, 6 months). Weight concerns also improved significantly when compared with baseline (3 months, +20, P < 0.001; 6 months, +14, P = 0.012). Symptoms of diarrhoea (3 months, --17, P = 0.007; 6 months,--16, P = 0.008) and nausea (--8, P = 0.032) improved. CONCLUSION: In patients with incurable metastatic CRC, surgery improved QOL.
Assuntos
Neoplasias Colorretais/cirurgia , Cuidados Paliativos/psicologia , Qualidade de Vida , Idoso , Ansiedade/etiologia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/métodos , Estudos Prospectivos , Inquéritos e QuestionáriosAssuntos
Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Pessoal de Saúde , Controle de Infecções/métodos , Exposição Ocupacional , Coqueluche/epidemiologia , Coqueluche/prevenção & controle , Criança , Pré-Escolar , Transmissão de Doença Infecciosa/prevenção & controle , Hospitais Pediátricos , Humanos , Incidência , Estudos Retrospectivos , Singapura/epidemiologia , Centros de Atenção TerciáriaAssuntos
Surfactantes Pulmonares/deficiência , Síndrome do Desconforto Respiratório do Recém-Nascido/genética , Aberrações Cromossômicas , Diagnóstico Diferencial , Feminino , Genes Recessivos/genética , Humanos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Recém-Nascido , Pulmão/patologia , Proteolipídeos/genética , Surfactantes Pulmonares/genética , Síndrome do Desconforto Respiratório do Recém-Nascido/patologiaRESUMO
An interesting and unusual case of abdominal aortic aneurysm with Leriche syndrome that presented with multiple vasculopathies and peptic ulcer is being reported.