Comparison of 2 Studies of Treatment of Invasive Aspergillosis (original) (raw)
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Cancer, 2007
BACKGROUND.Invasive aspergillosis (IA) has a poor prognosis in immunocompromised patients. Combinations of drugs that act on different targets are expected to improve the clinical efficacy of separate compounds.Invasive aspergillosis (IA) has a poor prognosis in immunocompromised patients. Combinations of drugs that act on different targets are expected to improve the clinical efficacy of separate compounds.METHODS.Patients with proven or probable IA were randomized in a prospective, open pilot study to receive either a combination of liposomal amphotericin B (AmB) at the standard dose (3 mg/kg daily) and caspofungin at the standard dose or monotherapy with a high-dose AmB regimen (10 mg/kg daily).Patients with proven or probable IA were randomized in a prospective, open pilot study to receive either a combination of liposomal amphotericin B (AmB) at the standard dose (3 mg/kg daily) and caspofungin at the standard dose or monotherapy with a high-dose AmB regimen (10 mg/kg daily).RESULTS.Thirty patients (21 men and 9 women) with hematologic malignancies were analyzed, and there were 15 patients in each arm. The median duration of treatment was 18 days for the combination group and 17 days for the high-dose monotherapy group. At the end of treatment, there were significantly more favorable overall responses (partial or complete responses; P = .028) in the combination group (10 of 15 patients; 67%) compared with the high-dose monotherapy group (4 of 15 patients; 27%). Survival rates at 12 weeks after inclusion were 100% and 80%, respectively. Infusion-related reactions occurred in 3 patients in the high-dose monotherapy group. A 2-fold increase in serum creatinine occurred in 4 of 17 patients (23%) who received high-dose monotherapy and 1 of 15 patient (7%) who received combination therapy; hypokalemia <3 mmol/L occurred in 3 patients and 2 patients, respectively.Thirty patients (21 men and 9 women) with hematologic malignancies were analyzed, and there were 15 patients in each arm. The median duration of treatment was 18 days for the combination group and 17 days for the high-dose monotherapy group. At the end of treatment, there were significantly more favorable overall responses (partial or complete responses; P = .028) in the combination group (10 of 15 patients; 67%) compared with the high-dose monotherapy group (4 of 15 patients; 27%). Survival rates at 12 weeks after inclusion were 100% and 80%, respectively. Infusion-related reactions occurred in 3 patients in the high-dose monotherapy group. A 2-fold increase in serum creatinine occurred in 4 of 17 patients (23%) who received high-dose monotherapy and 1 of 15 patient (7%) who received combination therapy; hypokalemia <3 mmol/L occurred in 3 patients and 2 patients, respectively.CONCLUSIONS.The combination of liposomal AmB and caspofungin was promising as therapy for IA compared with monotherapy. A trial that includes more patients will be required next to confirm the results of this pilot study. Cancer 2007. © 2007 American Cancer Society.The combination of liposomal AmB and caspofungin was promising as therapy for IA compared with monotherapy. A trial that includes more patients will be required next to confirm the results of this pilot study. Cancer 2007. © 2007 American Cancer Society.
Bone Marrow Transplantation, 2002
The management of invasive aspergillosis in patients with hematological malignancies remains controversial. A major problem is how to manage patients who had invasive aspergillosis during remission induction and consolidation therapy and then undergo SCT. Indeed in these patients the mortality rate related to invasive aspergillosis recurrence remains unacceptably high. We report two cases of patients who underwent remission induction for AML, developed invasive aspergillosis during antifungal prophylaxis with itraconazole, failed amphotericin B deoxycholate and liposomal amphotericin B treatment, were successfully treated with voriconazole and eventually underwent SCT with voriconazole prophylaxis without reactivation of invasive aspergillosis.
Transplant Infectious Disease, 2007
Abstract: Background. Voriconazole, a broad-spectrum triazole, has demonstrated significantly improved survival compared with conventional amphotericin B (CAB) as initial therapy for invasive aspergillosis (IA).Objective. To compare health care resource use and cost at 12 weeks following first-line treatment with voriconazole compared with CAB for IA using resource use data collected during a clinical trial.Methods. Days of hospitalization, intensive care, antifungal drug use, and outpatient care were collected during a large randomized, controlled trial of patients with IA receiving initial treatment with voriconazole or CAB. Unit costs based on published data sources were applied to healthcare use to estimate 12-week costs following initiation of therapy. Resource use and costs were compared for each treatment arm overall and by survival. The sensitivity of total costs to changes in healthcare use and unit costs was examined.Results. Total hospital days and intensive care unit (ICU) days were similar for voriconazole and CAB (total: 27.8 vs. 27.7, P=0.97 and ICU: 5.6 vs. 8.1, P=0.11). Among survivors, voriconazole was associated with similar numbers of total hospital days (29.8 vs. 32.0 days, P=0.54) to CAB, but fewer ICU days (3.9 vs. 8.2, P=0.03). For non-survivors, those treated with voriconazole had a similar number of total hospital days (23.0 vs. 21.8, P=0.73) and ICU days (9.8 vs. 7.9, P=0.44). Patients treated with voriconazole had significantly more days alive and out of the hospital than with CAB at 12 weeks (40.3 vs. 28.4 days, P<0.001). Total costs were similar with voriconazole compared with CAB ($78,860 vs. $83,857, P=0.51). Differences in cost were not sensitive to changes in the input parameter values.Conclusions. Using voriconazole first-line for treatment of IA resulted in significantly fewer deaths and similar treatment costs. Hospital-free survival was significantly greater for patients initially treated with voriconazole.
Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis
… England Journal of …, 2002
Background Voriconazole is a broad-spectrum triazole that is active against aspergillus species. We conducted a randomized trial to compare voriconazole with amphotericin B for primary therapy of invasive aspergillosis. Methods In this randomized, unblinded trial, patients received either intravenous voriconazole (two doses of 6 mg per kilogram of body weight on day 1, then 4 mg per kilogram twice daily for at least seven days) followed by 200 mg orally twice daily or intravenous amphotericin B deoxycholate (1 to 1.5 mg per kilogram per day). Other licensed antifungal treatments were allowed if the initial therapy failed or if the patient had an intolerance to the first drug used. A complete or partial response was considered to be a successful outcome. Results A total of 144 patients in the voriconazole group and 133 patients in the amphotericin B group with definite or probable aspergillosis received at least one dose of treatment. In most of the patients, the underlying condition was allogeneic hematopoietic-cell transplantation, acute leukemia, or other hematologic diseases. At week 12, there were successful outcomes in 52.8 percent of the patients in the voriconazole group (complete responses in 20.8 percent and partial responses in 31.9 percent) and 31.6 percent of those in the amphotericin B group (complete responses in 16.5 percent and partial responses in 15.0 percent; absolute difference, 21.2 percentage points; 95 percent confidence interval, 10.4 to 32.9). The survival rate at 12 weeks was 70.8 percent in the voriconazole group and 57.9 percent in the amphotericin B group (hazard ratio, 0.59; 95 percent confidence interval, 0.40 to 0.88). Voriconazole-treated patients had significantly fewer severe drug-related adverse events, but transient visual disturbances were common with voriconazole (occurring in 44.8 percent of patients). Conclusions In patients with invasive aspergillosis, initial therapy with voriconazole led to better responses and improved survival and resulted in fewer severe side effects than the standard approach of initial therapy with amphotericin B.
Invasive aspergillosis in acute myeloid leukemia: Are we making progress in reducing mortality?
Medical Mycology, 2016
The incidence of invasive fungal disease (IFD) has varied during the last decades. However, over the years, we have observed a progressive reduction of mortality, mainly due to wider use of prophylactic antifungal therapy (i.e., new azoles, such as posaconazole), the development of new and more effective antifungal drugs (lipid compounds of amphotericin B, candins, and azoles of the previous generation) and improvement of diagnostic tools. Based on a number of international studies across three decades, the attributable mortality rate for IFD and invasive aspergillosis (IA) among patients with acute myeloid leukemia (AML) has progressively declined. In the first report, in 2001, the attributable mortality rate for aspergillosis observed in AML patients by the GIMEMA (Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto) group was near 60%. A subsequent multicenter Italian study by SEIFEM (Sorveglianza Epidemiologica Infezioni Fungine nelle Emopatie Maligne) reported an attributable mortality of 38% among 3,012 patients recruited from 1999 through 2003. Further reduction to 27% was reported for patients diagnosed between 2004 and 2007 in another SEIFEM study. Over the last few years, a different trend in mortality for IA has been observed in the various phases of therapy in patients with acute leukemia: while in the induction phase of treatment, characterized by a higher incidence of IA, we observed a reduction of mortality over the years, among relapsed/refractory patients, the mortality remains dramatically high.