Hiramatsu, Y., Maeda, Y., Fujii, N., Saito, T., Nawa, Y., Hara, M., . . . West-Japan Hematology and Oncology Group. (2008). Use of micafungin versus fluconazole for antifungal prophylaxis in neutropenic patients receiving hematopoietic stem cell transplantation. International Journal of Hematology, 88, 588–595.

The hypothesis was that micafungin (150 mg) is a safe and effective alternative to fluconazole (400 mg) for the use of antifungal prophylaxis during neutropenia.

Patients were randomly assigned to receive either micafungin or fluconazole treatment using a 1:1 schedule.  Randomization was stratified according to the risk or transplant-related mortality.  High risk included acute leukemia in relapse or in complete remission for at least the third time, chronic myelogenous leukemia other than the first chronic phase, Hodgkin lymphoma or non-Hodgkin lymphoma in relapse or greater than or equal to the second complete or partial remission, myelodysplastic syndrome, or myeloproliferative syndrome.  Low risk included all factors not classified as high risk and any type of transplant (i.e., autologous, allogeneic using peripheral blood stem cells or bone marrow, or allogeneic using cord blood).  Groups received either 150 mg of micafungin or 400 mg of fluconazole daily by infusion until the earliest of: (1) absolute neutrophil count (ANC) of 500 cells/mm³ or greater, (2) 42 days after hematopoietic stem cell transplantation (HSCT), (3) development of proven, probable, or suspected invasive fungal infection, (4) development of unacceptable drug toxicity, or (5) other reason for withdrawal or discontinuation of treatment.  Antifungals were given within 48 hours of initiation of the transplant conditioning treatment.

• One hundred four patients were evaluable (52 patients in each arm).  
• Mean age was 46.5 years (range 16–67) in the micafungin arm and 47.3 years (range 18–65) in the fluconazole arm.
• In the micafungin arm, 64% of patients were male and 36% were female.  In the fluconazole arm, 68% of patients were male and 32% were female.
• Key disease characteristics were malignant lymphoma (46% in the micafungin arm, 44% in the fluconazole arm), multiple myeloma (18% in the micafungin arm, 26% in the fluconazole arm), acute myeloid leukemia (AML) (14% in the micafungin arm, 12% in the fluconazole arm); myelodysplastic syndrome (MDS) (10% in the micafungin arm, 8% in the fluconazole arm); acute lymphoblastic leukemia (ALL) (6% in both arms), and other hematologic malignancy/nonmalignant disease (6% in the micafungin arm, 4% in the fluconazole arm).  
• Transplant type included autologous HSCT in 48% of patients in both arms and allogeneic HSCT in 52% of patients in both arms.  Peripheral blood was used in all autologous HSCTs, allogeneic bone marrow or peripheral blood was used in 38% of patients in the micafungin arm and 44% in the fluconazole arm, and cord blood was used in 14% of patients in the micafungin arm and 8% in the fluconazole arm.

• Mutli-site  
• Inpatient
• Patients were hospitalized at the hematology departments of six study sites in Japan.

Patients were undergoing the active treatment phase of care.

This was a prospective, randomized, open-label comparative trial.

• Treatment success was defined as an absence of proven, probable, or suspected systemic fungal infection through a four-week period.     
• Definitions of the Fungal Infections Cooperative Group of the Suropena Organization for Research and Treatment of Cancer, National Institute of Allergy and Infectious Diseases Mycoses Study Group were used.
   

Neutrophil recovery was seen in an average of 13.7 days in both arms.  Graft-versus-host disease was present in 24% of patients in the micafungin arm and 30% in the fluconazole arm.  Overall treatment success, defined as the absence of proven, probable, or suspected systemic fungal infection through the end of prophylaxis therapy and as the absence of a proven or probable systemic fungal infection through the end of the four-week posttreatment period, was comparable in both arms, with 94% in the micafungin arm and 88% in the fluconazole arm.  This was not a significant difference.

The study showed that another class of medications, the echinocandins, can be effective in preventing fungal infections.  Its effectiveness is comparable to that of fluconazole, which is considered the gold standard for antifungal prophylaxis.  Neither drug had significant side effects, although the incidence was slightly higher with the use of micafungin.

This was an open-label study and was not powered to measure success rate differences.

Patients should be educated regarding the use, effectiveness, side effects of the medications, and need for continued antifungal prophylaxis based on risk.