Asunto(s)
Anemia de Células Falciformes , Transfusión de Eritrocitos/métodos , Hipertensión , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/complicaciones , Anemia de Células Falciformes/fisiopatología , Anemia de Células Falciformes/terapia , Transfusión de Eritrocitos/instrumentación , Femenino , Estudios de Seguimiento , Humanos , Hipertensión/sangre , Hipertensión/etiología , Hipertensión/fisiopatología , Hipertensión/terapia , MasculinoRESUMEN
This multicenter phase I/II study investigated the maximum tolerated dose (MTD), safety, and efficacy of low dose intravenous (IV) melphalan in combination with bortezomib for patients with relapsed multiple myeloma (MM). Patients received bortezomib 1.3 mg/m(2) on days 1, 4, 8, and 11 and escalating doses of IV melphalan (2.5-10.0 mg/m(2)) on day 2 of a 28-day cycle for a maximum of eight cycles. Dexamethasone 20 mg was added for progressive or stable disease. Fifty-three patients were enrolled. The MTD was defined at melphalan 7.5 mg/m(2) and bortezomib 1.3 mg/m(2). The overall response rate (ORR) was 68% (23% complete or near-complete responses [CR/nCR]) whilst at the MTD (n = 33) the ORR was 76% (34% CR/nCR). After median follow-up of 17 months, the median progression free survival was 10 months, rising to 12 months at the MTD (P < 0.05 vs. non-MTD regimens). The median overall survival was 28 months, but was not yet reached at the MTD. Grade 3/4 adverse events included thrombocytopenia (62%), neutropenia (57%), infection (21%), and neuropathy (15%). Bortezomib and low-dose IV melphalan combination therapy is a safe and highly effective regimen for patients with relapsed MM. These data suggest further investigation of this combination is warranted.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/administración & dosificación , Ácidos Borónicos/efectos adversos , Ácidos Borónicos/uso terapéutico , Bortezomib , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Dexametasona/uso terapéutico , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intravenosas , Estimación de Kaplan-Meier , Masculino , Dosis Máxima Tolerada , Melfalán/administración & dosificación , Melfalán/efectos adversos , Melfalán/uso terapéutico , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , Pirazinas/uso terapéutico , Recurrencia , Estadísticas no Paramétricas , Trombocitopenia/inducido químicamenteRESUMEN
Bortezomib, doxorubicin and dexamethasone (PAD) was evaluated as induction before stem cell transplantation in newly diagnosed multiple myeloma (MM) patients, using bortezomib 1.3 mg/m(2) (PAD1, N = 21) or 1.0 mg/m(2) (PAD2, N = 20). Complete/very good partial response rates with PAD1/PAD2 were 62%/42% postinduction and 81%/53% post-transplant. Progression-free survival (29 vs. 24 months), time to re-treatment (36 vs. 29 months) and overall survival (1 year: 100% vs. 95%; 2 years: 95% vs. 73%) were statistically similar but favoured PAD1 versus PAD2. Toxicity was lower in PAD2; bortezomib dose reduction may help manage toxicities while retaining efficacy. PAD is highly active as front-line induction in MM.
