Homoharringtonine: a new treatment option for myeloid leukemia.
HHT, one of the alkaloids from a Chinese natural plant, Cephalotaxus, has shown its potential in leukemia treatment. This compound demonstrated strong growth-inhibiting activities in vitro and in animal experiments, and obtained encouraging results in some clonal proliferative disease such as in chronic myeloid leukemia (CML) and in polycythemia vera. Evidences also confirmed HHT as an apoptosis inducer in tumor cell lines and fresh cells from cancer patients. The CR rate reported with HHT-based regimen in acute nonlymphocytic leukemia showed no statistic differences from that with DNR-based regimen, although the case number was limited. While used in clinical trial, the drug often cause noticeably cardiovascular disturbances if be given rapidly by intravenous infusion. Myelosuppression is the common complication in HHT-based chemotherapy. Although with the anti-growth activity in vitro and praisable achievement in acute and chronic myeloid leukemia treatment, the drug shows no beneficial effect in lymphocytic leukemia and solid tumors. The underlying mechanism for the discrepancy of efficacy keeps unknown. This review will present with the preclinical research data including the action mechanism, pharmacokinetics and drug resistance of HHT as well as the result from the clinical trial with HHT in China and the United States.
Luo
Chang Ying
CY
Department of Hematology/Oncology, Xin Hua Hospital/Shanghai Children's Medical Center, Shanghai Second Medical University, China.
Tang
Jing Yan
JY
Wang
Yao Ping
YP
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000139:chemically induced; D049109:Cell Proliferation / Q000187:drug effects; D032483:Cephalotaxus / Q000737:chemistry; D002986:Clinical Trials as Topic; D006248:Harringtonines / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000077863:Homoharringtonine; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D011086:Polycythemia / Q000188:drug therapy / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D006248:Harringtonines; D000077863:Homoharringtonine