RESUMEN
Febrile neutropenia is often observed in patients with hematologic malignancies, especially in those with acute leukemia. Meropenem has potent and broad antibacterial activity against gram-positive and gram-negative bacteria, and is recommended as first-line empiric therapy for febrile neutropenia. In contrast, the safety and efficacy of doripenem in patients with febrile neutropenia and hematologic malignancies is limited. In this randomized, prospective, cooperative, open-label trial, we compared doripenem (1.0 g every 8 h) to meropenem (1.0 g every 8 h) as first-line empiric antibacterial treatment of febrile neutropenia. To evaluate efficacy and safety, 133 hospitalized patients with acute leukemia or high-risk myelodysplastic syndrome, who developed febrile neutropenia during or after chemotherapy, were randomized to each drug. Resolution of fever within 3 to 5 days without treatment modification (i.e., the primary endpoint) did not significantly differ between the doripenem and meropenem groups (60.0% vs. 45.6%, respectively; P = 0.136). However, resolution of fever within 7 days of treatment was significantly higher in the doripenem group than in the meropenem group (78.4% vs. 60.2%, respectively; P = 0.037). Similar rates of adverse events (grades 1-2) were observed in both groups. Thus, we conclude that both drugs are safe and well-tolerated for the treatment of febrile neutropenia in patients with acute leukemia or high-risk myelodysplastic syndrome, and that the clinical efficacy of doripenem is noninferior to that of meropenem. UMIN Clinical Trial Registry number: 000006124.
Asunto(s)
Neutropenia Febril Inducida por Quimioterapia/tratamiento farmacológico , Doripenem/administración & dosificación , Leucemia/tratamiento farmacológico , Meropenem/administración & dosificación , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Doripenem/efectos adversos , Femenino , Fiebre/tratamiento farmacológico , Humanos , Masculino , Meropenem/efectos adversos , Persona de Mediana Edad , Síndromes Mielodisplásicos/tratamiento farmacológico , Estudios ProspectivosRESUMEN
OBJECTIVES: We conducted a phase-II study to evaluate the efficacy and safety of dasatinib in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP) in Japan (IMIDAS PART 2 study). METHODS: Seventy-nine patients were administered 100 mg dasatinib once daily. We examined pretreatment and post-treatment influences of various factors. The BCR-ABL1 international scale (IS), halving time (HT) and reduction rate of BCR-ABL1 transcript within the initial 1 or 3 months of therapy (RR-BCR-ABL11m,3m ) were the post-treatment factors investigated to predict the molecular response. RESULTS: The estimated major molecular response (MMR), molecular response 4.0 (MR4.0) and molecular response 4.5 (MR4.5) rates were 77.2%, 49.4% and 35.4%, respectively, at 12 months. Grade 3/4 non-haematologic adverse events were infrequent. Multivariate analysis showed that age >65 years was significantly correlated with MR4.0 and MR4.5 (deep molecular response: DMR) at 12 months. All post-treatment factors at 3 months predicted DMR by univariate analysis. However, RR-BCR-ABL13m was the only significant landmark for predicting DMR by multivariate analysis. CONCLUSIONS: Primary treatment of CML-CP with dasatinib enabled early achievement of MMR and DMR, particularly in elderly patients, with high safety. Furthermore, RR-BCR-ABL13m was found to be a more useful predictor of DMR than HT-BCR-ABL1 and BCR-ABL1 IS.
Asunto(s)
Antineoplásicos/uso terapéutico , Dasatinib/uso terapéutico , Proteínas de Fusión bcr-abl/genética , Expresión Génica , Leucemia Mieloide de Fase Crónica/tratamiento farmacológico , Leucemia Mieloide de Fase Crónica/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Dasatinib/administración & dosificación , Dasatinib/efectos adversos , Femenino , Humanos , Leucemia Mieloide de Fase Crónica/diagnóstico , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: We aimed to investigate the long-term outcomes of patients undergoing hybrid catheter intervention for acute massive pulmonary thromboembolism. MATERIAL AND METHODS: Twenty-five patients with hemodynamic impairment were treated with mechanical thrombus fragmentation, an intrapulmonary injection of mt-PA, and manual clot aspiration between August 1999 and June 2002. All patients were discharged after the procedure. Patients' statuses were checked by medical record examinations and telephone interviews. The median follow-up was 141 months (115-168 months). RESULTS: Ten patients died during follow-up, five for malignancy, three for septic shock, one for cerebral infarction, and one for heart failure. One patient had recurrence of pulmonary thromboembolism because of drug withdrawal by self-judgment. No chronic pulmonary thromboembolism was observed. The 1-year, 5-year, and 10-year survival rates were 87.5 ±6.8%, 83.3±7.6%, and 74.5±9.0%, respectively. CONCLUSION: Patients who undergo hybrid catheter intervention for acute massive pulmonary thromboembolism show good long-term outcomes.