title: Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia.
abstract: The potential mechanism of the chemotherapy resistance in acute myeloid leukemia (AML) is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is often overexpressed in myeloblasts from acute myeloid leukemia. In a multicenter clinical trial, 38 patients with poor risk forms of AML were treated with tetrandrine (TET), a potent inhibitor of the MDR-1 efflux pump, combined with daunorubicin (DNR), etoposide and cytarabine (TET-DEC). Overall, post-chemotherapy marrow hypoplasia was achieved in 36 patients. Sixteen patients (42%) achieved complete remission or restored chronic phase, 9 achieved partial remission (PR) and 13 failed therapy. Toxicities included infection, myelosuppression, stomatitis, mucositis, cerebellar toxicity and reversible cardiotoxicity. There was no significant difference in response for P-gp-positive and -negative patients. P-gp function was assessed in 26 patients by flow cytometric analysis, TET-contained plasma-augmented DNR accumulation relative to pretreatment plasma in K562/A02 cells by a median value of 88+/-101% (range, 11-501%). However, there was no difference in DNR uptake between responding and non-responding patients. Our data showed that TET-DEC was relatively well tolerated in these patients with poor risk AML, and had encouraging antileukemic effects.
authors.affiliation: Department of Hematology, The Affiliated People's Hospital, Jiangsu University, 8 Dianli Road, Zhenjiang 212002, PR China. xw10806@163.com
authors.forename: Wen-Lin
authors.initials: WL
authors.lastname: Xu
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Shen
authors.forename: Zhong-Fang
authors.initials: ZF
authors.lastname: Ao
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Xia
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.forename: Yong-Ning
authors.initials: YN
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000470:Alkaloids / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044182:Benzylisoquinolines / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005434:Flow Cytometry; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D012008:Recurrence
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000470:Alkaloids; D044182:Benzylisoquinolines; D003561:Cytarabine; C009438:tetrandrine; D005047:Etoposide; D003630:Daunorubicin