Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Dexametasona/uso terapéutico , Lenalidomida/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/efectos adversos , Estudios de Seguimiento , Humanos , Lenalidomida/efectos adversos , Mieloma Múltiple/terapia , Trasplante de Células Madre , Trasplante AutólogoRESUMEN
Clinical trials of vorinostat, a Class I/II histone deacetylase inhibitor, in combination with proteasome inhibitors and immunomodulatory agents have shown activity in relapsed/refractory multiple myeloma. This phase IIb, open-label, single-institution study evaluated the efficacy of vorinostat in combination with lenalidomide and dexamethasone in lenalidomide-refractory patients. Patients were considered lenalidomide-refractory if they had no clinical response (Asunto(s)
Dexametasona/administración & dosificación
, Ácidos Hidroxámicos/administración & dosificación
, Mieloma Múltiple/tratamiento farmacológico
, Terapia Recuperativa/métodos
, Talidomida/análogos & derivados
, Anciano
, Anciano de 80 o más Años
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
, Supervivencia sin Enfermedad
, Femenino
, Humanos
, Lenalidomida
, Masculino
, Persona de Mediana Edad
, Mieloma Múltiple/complicaciones
, Inducción de Remisión
, Terapia Recuperativa/efectos adversos
, Talidomida/administración & dosificación
, Resultado del Tratamiento
, Vorinostat
RESUMEN
Research has shown that proteasome inhibitors (e.g., carfilzomib), immunomodulatory agents (e.g., lenalidomide), histone deacetylase inhibitors (e.g., vorinostat) and corticosteroids (e.g., dexamethasone) have synergistic anti-multiple myeloma (MM) activity. This phase I dose-escalation study evaluated a regimen combining carfilzomib, lenalidomide, vorinostat and dexamethasone (QUAD) in patients with relapsed and/or refractory MM. Seventeen patients received carfilzomib (15, 20, or 20/27 mg/m(2) ; 30-min infusion; days 1, 2, 8, 9, 15, 16), lenalidomide (15 or 25 mg; days 1-21), vorinostat (300 or 400 mg; days 1-7, 15-21), and dexamethasone (40 mg; days 1, 8, 15, 22) in 28-d cycles. No dose-limiting toxicities were observed; the maximum tolerated dose was not reached. The maximum administered dose was carfilzomib 20/27 mg/m(2) , lenalidomide 25 mg, vorinostat 400 mg, and dexamethasone 40 mg. Common grade ≥3 adverse events included neutropenia (53%), thrombocytopenia (53%) and anaemia (41%). The overall response rate was 53%: 12% of patients achieved a very good partial response (PR) and 41% of patients achieved a PR. At a median follow-up of 10 months, median progression-free survival was 12 months and median overall survival was not reached. Treatment with QUAD was feasible and had encouraging activity in patients with relapsed and/or refractory MM.
