title: A multicenter phase 2 study of empirical low-dose liposomal amphotericin B in patients with refractory febrile neutropenia.
abstract: Invasive fungal infection (IFI) is a major life-threatening problem encountered by patients with hematological malignancies receiving intensive chemotherapy. Empirical antifungal agents are therefore important. Despite the availability of antifungal agents for such situations, the optimal agents and administration methods remain unclear. We conducted a prospective phase 2 study of empirical 1 mg/kg/day liposomal amphotericin B (L-AMB) in 80 patients receiving intensive chemotherapy for hematological malignancies. All enrolled patients were high-risk and had recurrent prolonged febrile neutropenia despite having received broad-spectrum antibacterial therapy for at least 72 hours. Fifty-three patients (66.3 %) achieved the primary endpoint of successful treatment, thus exceeding the predefined threshold success rate. No patients developed IFI. The treatment completion rate was 73.8 %, and only two cases ceased treatment because of adverse events. The most frequent events were reversible electrolyte abnormalities. We consider low-dose L-AMB to provide comparable efficacy and improved safety and cost-effectiveness when compared with other empirical antifungal therapies. Additional large-scale randomized studies are needed to determine the clinical usefulness of L-AMB relative to other empirical antifungal therapies.
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan. koutarou380@med.nagoya-u.ac.jp.|Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. koutarou380@med.nagoya-u.ac.jp.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Miyao
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sawa
authors.affiliation: Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.|Center for Supporting Hematology-Oncology Trials, Nagoya, Japan.
authors.forename: Mio
authors.initials: M
authors.lastname: Kurata
authors.affiliation: Department of HSCT Data Management and Biostatistics, Nagoya University, Nagoya, Japan.
authors.forename: Ritsuro
authors.initials: R
authors.lastname: Suzuki
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.|Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Reona
authors.initials: R
authors.lastname: Sakemura
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Sakai
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kato
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Sahashi
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Tsushita
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Yukiyasu
authors.initials: Y
authors.lastname: Ozawa
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Tsuzuki
authors.affiliation: Department of Hematology and Oncology, Konan Kosei Hospital, Konan, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kohno
authors.affiliation: Department of Hematology and Oncology, Chukyo Hospital, Nagoya, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Adachi
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.|Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Watanabe
authors.affiliation: Department of Hematology, Nishio Munishipal Hospital, Nishio, Japan.
authors.forename: Kaneyuki
authors.initials: K
authors.lastname: Ohbayashi
authors.affiliation: Department of Hematology and Oncology, Anjo Kosei Hospital, Anjo, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Inagaki
authors.affiliation: Japanese Data Center for Hematopoietic Cell Transplantation, Nagoya, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.affiliation: Department of Hematology, Fujita Health University, Toyoake, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Emi
mesh_terms: D000328:Adult; D000368:Aged; D000666:Amphotericin B / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D064147:Febrile Neutropenia / Q000150:complications*; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; C068538:liposomal amphotericin B; D000666:Amphotericin B
keywords: Antifungal therapy; Empirical therapy; Febrile neutropenia; Hematological malignancy; Liposomal amphotericin B