OBJECTIVES: Invasive fungal infections remain a frequent cause of morbidity and mortality in long-term neutropenic patients. The availability of tolerable broad-spectrum antifungals like voriconazole stimulated the discussion about optimal timing of antifungal therapy. We conducted a trial to analyze the efficacy and safety of voriconazole in the prevention of lung infiltrates during induction chemotherapy for acute myelogenous leukaemia (AML). METHODS: This was a prospective, randomised, double-blind, placebo-controlled phase III trial in AML patients undergoing remission induction chemotherapy. Oral voriconazole 200 mg twice daily or placebo was administered until detection of a lung infiltrate or end of neutropenia. Primary efficacy parameter was the incidence of lung infiltrates until day 21 after initiation of chemotherapy. Secondary objectives were incidence of infections, length of stay in hospital, time to antifungal treatment, time to first fever, and drug safety. RESULTS:A total of 25 patients were randomly assigned to receive voriconazole (N=10) or placebo (N=15). Incidence of lung infiltrates until day 21 was 0 (0%) in the voriconazole and 5 (33%) in the placebo group (P=0.06). Average length of stay in hospital was shorter in the voriconazole group (mean 31.9 days) than in the placebo group (mean 37.3 days, P=0.09). Four patients were diagnosed with hepatosplenic candidiasis until a 4 week follow-up, all in the placebo group (P=0.11). Adverse events and toxicity did not differ between the two treatment groups. The trial was stopped prematurely when another trial demonstrated reduced mortality by antifungal prophylaxis with posaconazole, thus rendering further randomisation against placebo unethical. CONCLUSION: In AML patients undergoing induction chemotherapy, prophylactic oral voriconazole 200 mg twice daily resulted in trends towards reduced incidences of lung infiltrates and hepatosplenic candidiasis. Voriconazole was safe and well tolerated.
RCT Entities:
OBJECTIVES: Invasive fungal infections remain a frequent cause of morbidity and mortality in long-term neutropenicpatients. The availability of tolerable broad-spectrum antifungals like voriconazole stimulated the discussion about optimal timing of antifungal therapy. We conducted a trial to analyze the efficacy and safety of voriconazole in the prevention of lung infiltrates during induction chemotherapy for acute myelogenous leukaemia (AML). METHODS: This was a prospective, randomised, double-blind, placebo-controlled phase III trial in AMLpatients undergoing remission induction chemotherapy. Oral voriconazole 200 mg twice daily or placebo was administered until detection of a lung infiltrate or end of neutropenia. Primary efficacy parameter was the incidence of lung infiltrates until day 21 after initiation of chemotherapy. Secondary objectives were incidence of infections, length of stay in hospital, time to antifungal treatment, time to first fever, and drug safety. RESULTS: A total of 25 patients were randomly assigned to receive voriconazole (N=10) or placebo (N=15). Incidence of lung infiltrates until day 21 was 0 (0%) in the voriconazole and 5 (33%) in the placebo group (P=0.06). Average length of stay in hospital was shorter in the voriconazole group (mean 31.9 days) than in the placebo group (mean 37.3 days, P=0.09). Four patients were diagnosed with hepatosplenic candidiasis until a 4 week follow-up, all in the placebo group (P=0.11). Adverse events and toxicity did not differ between the two treatment groups. The trial was stopped prematurely when another trial demonstrated reduced mortality by antifungal prophylaxis with posaconazole, thus rendering further randomisation against placebo unethical. CONCLUSION: In AMLpatients undergoing induction chemotherapy, prophylactic oral voriconazole 200 mg twice daily resulted in trends towards reduced incidences of lung infiltrates and hepatosplenic candidiasis. Voriconazole was safe and well tolerated.
Authors: Eric J Bow; Gerald Evans; Jeff Fuller; Michel Laverdière; Coleman Rotstein; Robert Rennie; Stephen D Shafran; Don Sheppard; Sylvie Carle; Peter Phillips; Donald C Vinh Journal: Can J Infect Dis Med Microbiol Date: 2010 Impact factor: 2.471
Authors: Oliver A Cornely; Angelika Böhme; Dieter Buchheidt; Hermann Einsele; Werner J Heinz; Meinolf Karthaus; Stefan W Krause; William Krüger; Georg Maschmeyer; Olaf Penack; Jörg Ritter; Markus Ruhnke; Michael Sandherr; Michal Sieniawski; Jörg-Janne Vehreschild; Hans-Heinrich Wolf; Andrew J Ullmann Journal: Haematologica Date: 2008-12-09 Impact factor: 9.941
Authors: E Ramírez; J García-Rodríguez; A M Borobia; J M Ortega; S Lei; A Barrios-Fernández; M Sánchez; A J Carcas; A Herrero; J M de la Puente; J Frías Journal: Eur J Clin Microbiol Infect Dis Date: 2011-07-01 Impact factor: 3.267
Authors: Gloria N Mattiuzzi; Jorge Cortes; Gladys Alvarado; Srdan Verstovsek; Charles Koller; Sherry Pierce; Deborah Blamble; Stefan Faderl; Lianchun Xiao; Mike Hernandez; Hagop Kantarjian Journal: Support Care Cancer Date: 2009-12-03 Impact factor: 3.603