Efficacy and Safety Assessment of Antifungal Sequential Therapy from Micafungin to Liposomal Amphotericin B for Antibiotics-Refractory Febrile Neutropenia in Patients with Hematologic Malignancies
- 1 Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu, Japan
- 2 Department of Internal Medicine, Suzuka Kaisei Hospital, Kameyama, Japan
- 3 Department of Internal Medicine, Suzuka Chuo Hospital, Suzuka, Japan
- 4 Department of Internal Medicine, Takeuchi Hospital, Tsu, Japan
- 5 Department of Internal Medicine, Ise Red Cross Hospital, Ise, Japan
- 6 Department of Hematology and Oncology, Mie University Hospital, Tsu, Japan
Abstract
Invasive fungal infections are a major challenging problem in the management of febrile neutropenia (FN) in patients with hematologic malignancies. Liposomal amphotericin B (L-AmB) or micafungin (MCFG) has been widely used as a first-line empirical antifungal therapy for suspected fungal infection in such patients. However, there are several issues in patients receiving these agents: drug related toxicities for L-AmB and breakthrough fungal infections for MCFG. In order to make the best use of these 2 agents, we conducted a prospective study of sequential therapy from MCFG to L-AmB, and evaluated the efficacy and safety of this strategy in FN patients with hematologic malignancies. A total of 18 patients were enrolled, and 11 patients who fulfilled the protocol defined criteria were evaluated. Underlying diseases consisted of acute leukemia (n = 9), non-Hodgkin lymphoma (n = 1), and myelodysplastic syndrome (n = 1). Treatment success was achieved in 8 patients (72.7%). Drug-related adverse events occurred in 8 patients (72.7%). All of those adverse events except one case were below grade 2. Three patients required discontinuation of L-AmB. Although our empirical antifungal sequential therapy seems to be encouraging for antibiotics-refractory FN in patients with hematologic malignancies, further investigation in large-scale studies is warranted.
- Moreno, J.M., Alhambra, A., Cuétara, M.S., Ortiz, M.C., Pontón, J., del Palacio-Pérez-Medel, A., et al. (2006) Incidence of Invasive Fungal Infection in Adult Haematological Malignancy: A Prospective Validation of a Risk Stratification Scheme. British Journal of Haematology, 134, 343-345. https://doi.org/10.1111/j.1365-2141.2006.06180.x
- Chamilos, G., Lewis, R.E. and Kontoyiannis, D.P. (2008) Delaying Amphotericin B—Based Frontline Therapy Significantly Increases Mortality among Patients with Hematologic Malignancy Who Have Zygomycosis. Clinical Infectious Disease, 47, 503-509. https://doi.org/10.1086/590004
- Sugawara, Y., Nakase, K., Nakamura, A., Ohishi, K., Sugimoto, Y., Fujieda, A., et al. (2013) Clinical Utility of a Panfungal Polymerase Chain Reaction Assay for Invasive Fungal Diseases in Patients with Haematologic Disorders. European Journal of Haematology, 90, 331-339. https://doi.org/10.1111/ejh.12078
- Fraser, I.S. and Denning, D.W. (1993) Empiric Amphotericin B Therapy: The Need for a Reappraisal. Blood Reviews, 7, 208-214. https://doi.org/10.1016/0268-960X(93)90007-Q
- Prentice, H.G., Hann, I.M., Herbrecht, R., Aoun, M., Kvaloy, S., Catovsky, D., et al. (1997) A Randomized Comparison of Liposomal versus Conventional Amphotericin B for the Treatment of Pyrexia of Unknown Origin in Neutropenic Patients. British Journal of Haematology, 98, 711-718. https://doi.org/10.1046/j.1365-2141.1997.2473063.x
- Miyao, K., Sawa, M., Kurata, M., Suzuki, R., Sakemura, R., Sakai, T., et al. (2017) A Multicenter Phase 2 Study of Empirical Low-Dose Liposomal Amphotericin B in Patients with Refractory Febrile Neutropenia. International Journal of Hematology, 105, 79-86. https://doi.org/10.1007/s12185-016-2095-y
- Hamill, R.J. (2013) Amphotericin B Formulations: A Comparative Review of Efficacy and Toxicity. Drugs, 73, 919-934. https://doi.org/10.1007/s40265-013-0069-4
- Denning, D.W. (2003) Echinocandin Antifungal Drugs. The Lancet, 362, 1142-1151. https://doi.org/10.1016/S0140-6736(03)14472-8
- Toubai, T., Tanaka, J., Ota, S., Shigematsu, A., Shono, Y., Ibata, M., et al. (2007) Efficacy and Safety of Micafungin in Febrile Neutropenic Patients Treated for Hematological Malignancies. Internal Medicine, 46, 3-9. https://doi.org/10.2169/internalmedicine.46.6021
- Oyake, T., Kowata, S., Murai, K., Ito, S., Akagi, T., Kubo, K., et al. (2016) Comparison of Micafungin and Voriconazole as Empirical Antifungal Therapies in Febrile Neutropenic Patients with Hematological Disorders: A Randomized Controlled Trial. European Journal of Haematology, 96, 602-609. https://doi.org/10.1111/ejh.12641