Comparative clinical effectiveness of prophylactic voriconazole/posaconazole to fluconazole/itraconazole in patients with acute myeloid leukemia/myelodysplastic syndrome undergoing cytotoxic chemotherapy over a 12-year period

Abstract

Post-induction aplasia for acute myeloid leukemia/myelodysplastic syndrome is a high-risk period for invasive fungal diseases. The effectiveness of fluconazole, itraconazole solution, voriconazole and posaconazole prophylaxis used consecutively from December 1998 to January 2010 in patients with acute myeloid leukemia/ myelodysplastic syndrome undergoing remission-induction chemotherapy was retrospectively evaluated. A total of 216 consecutive patients received 573 prophylaxis courses. Breakthrough-invasive fungal disease incidence in fluconazole, itraconazole, voriconazole, posaconazole recipients was 25%, 16%, 14% and 3%, respectively. Voriconazole/posconazole versus fluconazole/itraconazole combined was associated with significant reductions in breakthrough-invasive fungal disease incidence (20% vs

Incidence Density of Invasive Fungal Infections during Primary Antifungal Prophylaxis in Newly Diagnosed Acute Myeloid Leukemia Patients in a Tertiary Cancer Center, 2009 to 2011

“…Despite a pivotal, multi-institutional study (12) and several guidelines (15,17,18), the intensity (i.e., broad-versus narrowspectrum antifungals) and duration of PAP in patients with AML are still a matter of debate (3,13,14). The balance between overtreating patients who might never develop IFI and unfavorable treatment outcomes for patients who develop IFIs because of delays in treatment initiation has tipped in favor of PAP, specifically involving anti-Aspergillus drugs (7,9,10,12,14,15,19). The ideal antifungal for prophylaxis should have potent extended-spectrum activity for both oral and parenteral use and be well tolerated (1,14), with reasonable cost, characteristics not found in a single antifungal drug.…”

“…The incidence of documented IFIs (definite or probable, according to revised European Organization for Research and Treatment of Cancer [EORTC] criteria) has been reported to range from 12 to 34% in patients with AML (4)(5)(6)(7)(8)(9)(10). In contrast, lower rates of 2 to 6% have been reported for selected patients with AML/myelodysplastic syndrome (MDS) who were enrolled in clinical trials of antifungal prophylaxis (11)(12)(13).…”

All trans retinoic acid induced hypercalcemia and diffuse alveolar hemorrhage in acute promyelocytic leukemia: Practical guidelines for diagnosis and treatment based on a case report and literature review

“…Table 1 summarizes the therapeutic strategies adopted. The question regarding the best strategy, stopping fungal prophylaxis [30] or ATRA, is not answered yet. Proposed level III guides for hypercalcemia associated with ATRA in APL are listed below:…”

The role of antifungal treatment in hematology

“…Nevertheless, an Australian observational study by Ananda-Rajah and colleagues comparing fluconazole/itraconazole versus voriconazole/posaconazole prophylaxis in AML/MDS patients supports the main findings of the clinical trial, namely a lower incidence of breakthrough invasive fungal disease (including possible diseases), and less empirical antifungal therapy. 6 In addition, posaconazole prophylaxis also resulted in a lower demand for CT scans, and when a chest CT scan was taken, fewer lesions were seen. However, unselected use of broad-spectrum antifungal prophylaxis also raises concerns about expenditure, overtreatment, toxicity and emergent drug-resistance.…”