RESUMEN
Previous studies suggest that idarubicin/cytarabine(ara-C)/pravastatin (IAP) is an active salvage regimen for patients with AML. We therefore investigated this regimen in patients with newly-diagnosed AML or MDS (≥10% blasts). Patients were eligible if the anticipated treatment-related mortality (TRM) was <10%. Patients received pravastatin (1,280 mg/day po; days 1-8), cytarabine (1.5 g/m(2) /day; days 4-7), and idarubicin (12 mg/m(2) /day, days 4-6). Up to 3 cycles of consolidation with a shortened course was permitted. The primary endpoints were "good CR" rate (CR on day 35 without minimal residual disease) and TRM in the first 28 days. The study was to stop if after each cohort of 5 patients (a) the Bayesian posterior probability was < 5% that the true "good CR rate" was ≥ 70% or (b) the posterior probability was >25% that the TRM rate was ≥5%. Twenty-four patients were included. Conventional CR was achieved in 15 (63%) patients but only 12 (50%) achieved "good CR". 4 of 12 (33%) patients with "good CR" relapsed at median of 16 weeks (10.5-19). Five (21%) patients had refractory disease. Survival probability at 1 year was 72% (48.7-64). Two (8.3%) patients died within 28 days from multiorgan failure. The most common grade 3-4 adverse effects were febrile neutropenia (75%) and diarrhea (25%). Based on the stopping rules accrual ceased after entry of these 24 patients. IAP did not meet the predefined efficacy criteria for success. Therefore, we would not recommend this regimen for phase three testing in this patient subset.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Quimioterapia de Inducción , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/mortalidad , Adolescente , Adulto , Anciano , Citarabina/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Idarrubicina/administración & dosificación , Masculino , Persona de Mediana Edad , Pravastatina/administración & dosificación , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND AND OBJECTIVE: Combined spinal-epidural is an alternative technique to epidural analgesia for labour, but its benefits are not clearly identified. METHODS: A prospective, blinded, randomized study was undertaken involving 113 women attending a university hospital obstetric department. Analgesia was initiated with intrathecal bupivacaine 0.25% 1 mL + sufentanil 5 microg in the combined spinal-epidural group (n = 54), and with bupivacaine 0.125% + epinephrine 2.5 microg mL(-1) + sufentanil 7.5 microg in the epidural group (n = 59). In both cases this was followed by patient-controlled epidural analgesia with bupivacaine 0.125% (+ sufentanil 0.25 microg mL(-1)). Duration of labour, quality of analgesia and side-effects were compared between groups. RESULTS: In the combined spinal-epidural group, the onset of analgesia was faster (5 vs. 15 min, P < 0.001), the consumption of bupivacaine was lower (7.5 vs. 11.3 mg h(-1), P = 0.003) and there was less unilateral analgesia (14.8% vs. 40.7%, P = 0.002) than in the epidural group. The characteristics of labour were similar in both groups. However, in the combined spinal-epidural group, there was a higher incidence of posterior presentation (25.9% vs. 10%, P = 0.03), pruritus (P < 0.001), hypotension (P = 0.002), somnolence (P = 0.01), nausea (P = 0.02) and one case of meningitis. CONCLUSIONS: The combined spinal-epidural technique provided more effective analgesia during labour than epidural analgesia alone but offered no other advantage. It induced more adverse effects and this should be considered before routinely using the combined spinal-epidural technique.