Background: To analyze the efficacy and safety of voriconazole in the prevention of lung infiltrates during induction chemotherapy for AML. Methods: Prospective, randomized, double-blind, placebo-controlled phase III trial in AML patients undergoing first remission induction chemotherapy. VCZ 200 mg bid or placebo (PLC) were to be given until detection of a lung infiltrate or end of neutropenia. Duration of expected neutropenia 9 days, age > 17 years, informed consent. Primary objective was the incidence of lung infiltrates until day 21, i.e. the start of 2nd induction chemotherapy. Other objectives were the incidence of fever, rate of patients with systemic open label antifungals, time to initiation of systemic open-label antifungal therapy, rate and type of breakthrough invasive fungal infections, incidence and severity of adverse events, pharmacogenetics, and pharmacokinetics, and overall costs. Results: 25 patients (female 8, male 17; age 19-73 years; body weight 54-132 kg; de novo AML 24, relapsed AML 1) were randomized to VCZ (n=10) or PLC (n=15). Reasons for end of prophylactic treatment were neutrophil recovery in 4 VCZ vs 2 PLC pts, 2nd induction chemotherapy in 0 vs 2, prophylactic course completed in 3 vs 2, lung infiltrate in 0 vs 3, empiric antifungals in 2 vs 2, other in 1 vs 4. Incidence of lung infiltrates until day 21was 0 (0%) in VCZ vs 5 (33%) in PLC (967;Â² test, p=0.04). Incidences of chronic disseminated candidiasis at 4 week follow-up was 0 (0%) in the VCZ vs. 4 (27%) in the PLC treatment group (967;Â² test, p=0.07). Conclusions: In this randomized, double-blind, placebo-controlled trial voriconazole 200 mg bid PO reduced the incidence of lung infiltrates during AML induction chemotherapy. Probable chronic disseminated candidiasis was more frequent in the placebo arm.
Full conference title:
46th Interscience Conference on Antimicrobial Agents and Chemotherapy
- ICAAC 46th