title: [Pilot late phase II study of KRN8602 (MX2), a novel anthracycline derivative, for acute leukemia--a dose finding study in combination].
abstract: In order to determine the clinically optimal dose of KRN8602, a new anthracycline derivative, in combination therapy for acute leukemia, we performed a pilot late phase II study in combination with cytarabine (Ara-C) for acute myelogenous leukemia (AML), and with vincristine (VCR) and prednisolone (PSL) for acute lymphocytic leukemia (ALL). KRN8602 was given at a dose of 12 or 15 mg/m2 for 5 consecutive days, Ara-C at a dose of 100 mg/m2 for 7 consecutive days, VCR 1.4 mg/m2 (max. 2.0 mg/body) weekly for 4 weeks, and PSL 40 mg/m2 for principally 28 consecutive days. Of 14 patients with relapsed or refractory leukemia entered in the study, thirteen patients were evaluable for safety and 12 were evaluable for response. In AML, there was 1 partial response (PR) in 4 patients at a dose of 12 mg/m2. Against 1 complete response (CR) and 3 PRs in 4 patients at a dose of 15 mg/m2. In ALL, there was 1 PR in 1 case at a dose of 12 mg/m2, and 1 CR and 2 PR in 3 at a dose of 15 mg/m2. Major toxicities were nausea/vomiting and anorexia, but incidences and grades of toxicities were not dose-dependent, and all toxicities were tolerable and manageable. From these results it is concluded that the optimal dose of KRN8602 is 15 mg/m2 for 5 consecutive days in combination with Ara-C for AML, and with VCR and PSL for ALL.
authors.affiliation: Dept. of Internal Medicine V, Osaka Medical Center for Cancer and Cardiovascular Diseases.
authors.forename: A
authors.initials: A
authors.lastname: Hiraoka
authors.forename: K
authors.initials: K
authors.lastname: Sampi
authors.forename: Y
authors.initials: Y
authors.lastname: Kuraishi
authors.forename: Y
authors.initials: Y
authors.lastname: Takemoto
authors.forename: K
authors.initials: K
authors.lastname: Okabe
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: M
authors.initials: M
authors.lastname: Ogawa
mesh_terms: D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002360:Carubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D003561:Cytarabine / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010865:Pilot Projects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D011239:Prednisolone / Q000008:administration & dosage; D012074:Remission Induction; D014750:Vincristine / Q000008:administration & dosage; D014840:Vomiting, Anticipatory / Q000209:etiology