Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia
2005; Elsevier BV; Volume: 30; Issue: 4 Linguagem: Inglês
10.1016/j.leukres.2005.08.005
ISSN1873-5835
AutoresWenlin Xu, Huiling Shen, Zhong-Fang Ao, Baoan Chen, Wei Xia, Feng Gao, Yong-Ning Zhang,
Tópico(s)DNA and Nucleic Acid Chemistry
ResumoThe 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, postchemotherapy 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.
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