title: A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML).
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Klinikum der Universität zu Köln, Klinik I für Innere Medizin, Studienzentrum Infektiologie II, 50937 Köln, Germany.
authors.forename: Jörg J
authors.initials: JJ
authors.lastname: Vehreschild
authors.forename: Angelika
authors.initials: A
authors.lastname: Böhme
authors.forename: Dieter
authors.initials: D
authors.lastname: Buchheidt
authors.forename: Dorothee
authors.initials: D
authors.lastname: Arenz
authors.forename: Urs
authors.initials: U
authors.lastname: Harnischmacher
authors.forename: Claus P
authors.initials: CP
authors.lastname: Heussel
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ullmann
authors.forename: Sabine
authors.initials: S
authors.lastname: Mousset
authors.forename: Margit
authors.initials: M
authors.lastname: Hummel
authors.forename: Peter
authors.initials: P
authors.lastname: Frommolt
authors.forename: Gernot
authors.initials: G
authors.lastname: Wassmer
authors.forename: Ivonne
authors.initials: I
authors.lastname: Drzisga
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Cornely
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D015994:Incidence; D007902:Length of Stay; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000188:drug therapy; D008172:Lung Diseases, Fungal / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000517:prevention & control*; D010919:Placebos / Q000008:administration & dosage; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D065819:Voriconazole