title: Phase I trial of gemtuzumab ozogamicin in intensive combination chemotherapy for relapsed or refractory adult acute myeloid leukemia (AML): Japan Adult Leukemia Study Group (JALSG)-AML206 study.
abstract: In order to investigate better molecular-target therapy for acute myeloid leukemia (AML), we conducted a phase I trial of a combination of gemtuzumab ozogamicin (GO) with conventional chemotherapy. Between January 2007 and December 2009, a total of 19 adult Japanese patients with relapsed or refractory CD33-positive AML (excluding acute promyelocytic leukemia) were enrolled. All registered patients received a standard dose of cytarabine (Ara-C) (100 mg/m(2) × 7 days), combined with either idarubicin (IDR) (10-12 mg/m(2) × 3 days) or daunorubicin (DNR) (50 mg/m(2) × 3-5 days), and then GO (3-5 mg/m(2) ), which was administered 1 day after the last infusion of IDR (IAG regimen) or DNR (DAG regimen). While doses of both GO and IDR and the administration period of only DNR were increased, the dose-limiting toxicity (DLT) was assessed. Among 19 patients (nine in the IAG regimen, 10 in the DAG regimen), the median age was 59 years (range 33-64), and the relapsed/refractory ratio was 13/6. In the therapy using 3 mg/m(2) GO in the IAG or DAG regimen, grade 3/4 leukopenia and neutropenia were observed in all patients, but none had grade 3/4 non-hematological toxicities, except febrile neutropenia. Three patients in the IAG regimen who were administered 5 mg/m(2) GO showed DLT. No patients had veno-occlusive disease or sinusoidal obstructive syndrome. In conclusion, 3 mg/m(2) GO combined with Ara-C and IDR or DNR can be safely administered, and phase II trials should be conducted to investigate the clinical efficacy of the combination therapy.
authors.affiliation: Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan. usuin@jikei.ac.jp
authors.forename: Noriko
authors.initials: N
authors.lastname: Usui
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takeshita
authors.forename: Chiaki
authors.initials: C
authors.lastname: Nakaseko
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Dobashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fujita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kiyoi
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Toru
authors.initials: T
authors.lastname: Sakura
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yahagi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Shigeno
authors.forename: Chikako
authors.initials: C
authors.lastname: Ohwada
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Shigeki
authors.initials: S
authors.lastname: Ohtake
authors.forename: Shuichi
authors.initials: S
authors.lastname: Miyawaki
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohnishi
mesh_terms: D000328:Adult; D000617:Aminoglycosides / Q000008:administration & dosage / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D000079982:Gemtuzumab; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3
chemical_list: D000617:Aminoglycosides; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D063268:Sialic Acid Binding Ig-like Lectin 3; D000079982:Gemtuzumab; D015255:Idarubicin; D003630:Daunorubicin