A study to determine the safety profile and maximum tolerated dose of micafungin (FK463) in patients undergoing haematopoietic stem cell transplantation.
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.
Sirohi
B
B
Leukaemia and Myeloma Unit, Royal Marsden Hospital, Sutton, Surrey, UK.
Powles
R L
RL
Chopra
R
R
Russell
N
N
Byrne
J L
JL
Prentice
H G
HG
Potter
M
M
Koblinger
S
S
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
D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D008074:Lipoproteins; D010456:Peptides, Cyclic; D000077551:Micafungin