title: A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation.
abstract: This open-label, dose-escalation study assessed the maximum tolerated dose (MTD) of the new antifungal micafungin in patients undergoing haematopoietic stem cell transplantation (HSCT). Participants received 3, 4, 6 or 8 mg/kg/day micafungin intravenously from 7 days to a maximum of 28 days or until neutropaenia resolved. The MTD was defined as the highest dose not causing the same Grade 3 or 4 adverse event in three or more patients. All 36 participants received >/=8 days treatment for a median of 18 days (range: 8-28); 1 patient withdrew consent and a further 11 discontinued to receive another systemic antifungal agent for a suspected infection. No case of confirmed invasive fungal infection occurred. Adverse events were those expected for patients undergoing HSCT and showed no evidence of dose-related toxicity. Criteria for MTD were not met; no patient had a Grade 3 or 4 adverse event considered causally related to micafungin. Thus, the MTD of micafungin can be inferred to be 8 mg/kg/day or higher.
authors.affiliation: Leukaemia and Myeloma Unit, Royal Marsden Hospital, Sutton, Surrey, UK.
authors.forename: B
authors.initials: B
authors.lastname: Sirohi
authors.forename: R L
authors.initials: RL
authors.lastname: Powles
authors.forename: R
authors.initials: R
authors.lastname: Chopra
authors.forename: N
authors.initials: N
authors.lastname: Russell
authors.forename: J L
authors.initials: JL
authors.lastname: Byrne
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
authors.forename: M
authors.initials: M
authors.lastname: Potter
authors.forename: S
authors.initials: S
authors.lastname: Koblinger
mesh_terms: D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004334:Drug Administration Schedule; D054714:Echinocandins; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007262:Infusions, Intravenous; D055666:Lipopeptides; D008074:Lipoproteins / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D020714:Maximum Tolerated Dose; D000077551:Micafungin; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000009:adverse effects*; D012449:Safety; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin