RESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mielomonocítica Crónica/tratamiento farmacológico , Leucemia Mielomonocítica Crónica/patología , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/patología , Administración Oral , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Azacitidina/administración & dosificación , Médula Ósea/patología , Femenino , Humanos , Ácidos Hidroxámicos/administración & dosificación , Indoles/administración & dosificación , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/mortalidad , Leucemia Mielomonocítica Crónica/mortalidad , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Síndromes Mielodisplásicos/mortalidad , Panobinostat , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Neoplasias Colorrectales/cirugía , Cuidados Paliativos/psicología , Calidad de Vida , Anciano , Ansiedad/etiología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Paliativos/métodos , Estudios Prospectivos , Encuestas y CuestionariosAsunto(s)
Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Personal de Salud , Control de Infecciones/métodos , Exposición Profesional , Tos Ferina/epidemiología , Tos Ferina/prevención & control , Niño , Preescolar , Transmisión de Enfermedad Infecciosa/prevención & control , Hospitales Pediátricos , Humanos , Incidencia , Estudios Retrospectivos , Singapur/epidemiología , Centros de Atención TerciariaAsunto(s)
Surfactantes Pulmonares/deficiencia , Síndrome de Dificultad Respiratoria del Recién Nacido/genética , Aberraciones Cromosómicas , Diagnóstico Diferencial , Femenino , Genes Recesivos/genética , Humanos , Hipertensión Pulmonar/genética , Hipertensión Pulmonar/patología , Recién Nacido , Pulmón/patología , Proteolípidos/genética , Surfactantes Pulmonares/genética , Síndrome de Dificultad Respiratoria del Recién Nacido/patologíaRESUMEN
An interesting and unusual case of abdominal aortic aneurysm with Leriche syndrome that presented with multiple vasculopathies and peptic ulcer is being reported.