carubicin and Leukemia--Myeloid

We conducted a phase II multicenter study in order to evaluate the efficacy and toxicity of two combination regimens containing KRN8602 (MX2) for drug-resistant acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). AML was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, and cytarabine (AraC), 100 mg/m2 by 24 h coutinuous infusion for 7 days. ALL was treated with KRN8602, 15 mg/m2 i.v. push for 5 days, vincristine (VCR), 1.4 mg/m2 i.v. push, once weekly, and prednisolone (PSL), 40 mg/m2, 3 h infusion for 5 days. In AML and ALL, the complete remission (CR) rate was 36.4% (16 of 44) and 24.1% (seven of 29), and the overall response rate (CR+PR) was 52.3% (23 of 44) and 51.7% (15 of 29), respectively. Among the 29 relapsed cases of AML, a higher CR rate, 51.7% (15 of 29), was obtained. A high incidence of nausea/vomiting and anorexia was observed, and some patients experienced central nervous system disorders and peripheral neuropathy. There was a low incidence of severe neurotoxicities; all other toxicities were manageable. KRN8602 was found to overcome drug resistance clinically, confirming results based on the preclinical studies. We conclude that KRN8602 is an effective novel anthracycline for drug-resistant acute leukemias.

Topics: Acute Disease; Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; ATP Binding Cassette Transporter, Subfamily B, Member 1; Carubicin; Cytarabine; Drug Resistance, Neoplasm; Female; Humans; Leukemia, Myeloid; Male; Middle Aged; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Treatment Failure; Vincristine

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Carubicin; Daunorubicin; Drug Evaluation; Drug Therapy, Combination; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Middle Aged; Time Factors