title: Prospective phase II single-center study of the safety of a single very high dose of liposomal amphotericin B for antifungal prophylaxis in patients with acute myeloid leukemia.
abstract: Some preclinical and pharmacokinetic studies suggested the variable safety and the potential efficacy of an antifungal prophylaxis with a single high dose of liposomal amphotericin B (L-AmB) in high-risk patients. An open-label, prospective study was conducted with 48 adults receiving induction chemotherapy for acute myeloid leukemia (AML). Patients received a single infusion of 15 mg/kg of body weight L-AmB and, eventually, a second dose after 15 days of persistent neutropenia. The primary objective was tolerability and safety. Efficacy was also evaluated as a secondary endpoint. A pharmacokinetic study was performed with 34 patients in order to evaluate any association of plasma L-AmB levels with toxicity and efficacy. Overall, only 6 patients (12.5%) reported Common Toxicity Criteria (CTC) grade 3 hypokalemia, which was corrected with potassium supplementation in all cases, and no patient developed clinically relevant nephrotoxicity. Mild infusion-related adverse events occurred after 6 of 53 (11.3%) total infusions, with permanent drug discontinuation in only one case. Proven invasive fungal disease (IFD) was diagnosed in 4 (8.3%) patients. The mean AmB plasma levels at 6 h, 24 h, and 7 days after L-AmB administration were 160, 49.5, and 1 mg/liter, respectively. The plasma AmB levels were higher than the mean values of the overall population in 3 patients who developed CTC grade 3 hypokalemia and did not significantly differ from the mean values of the overall population in 3 patients who developed IFD. Our experience demonstrates the feasibility and safety of a single 15-mg/kg L-AmB dose as antifungal prophylaxis in AML patients undergoing induction chemotherapy.
authors.affiliation: Unità di Ematologia, Azienda Ospedaliera San Giovanni Addolorata, Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Annino
authors.forename: Anna
authors.initials: A
authors.lastname: Chierichini
authors.forename: Barbara
authors.initials: B
authors.lastname: Anaclerico
authors.forename: Erica
authors.initials: E
authors.lastname: Finolezzi
authors.forename: Marianna
authors.initials: M
authors.lastname: Norata
authors.forename: Stefania
authors.initials: S
authors.lastname: Cortese
authors.forename: Maria Iris
authors.initials: MI
authors.lastname: Cassetta
authors.forename: Stefania
authors.initials: S
authors.lastname: Fallani
authors.forename: Andrea
authors.initials: A
authors.lastname: Novelli
authors.forename: Corrado
authors.initials: C
authors.lastname: Girmenia
mesh_terms: D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000150:complications / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000382:microbiology / Q000517:prevention & control*; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B