Warrell R P, Coonley C J, Gee T S
J Clin Oncol. 1985 May;3(5):617-21. doi: 10.1200/JCO.1985.3.5.617.
Homoharringtonine (HHT) is a new plant alkaloid originally isolated in the People's Republic of China. Preliminary studies have suggested antitumor activity in several neoplastic diseases. We treated 49 patients with relapsed or resistant acute leukemia with escalating doses of homoharringtonine administered by continuous infusion. Three dose levels were examined: 5 mg/m2 for seven days, 7 mg/m2 for seven days, and 5 mg/m2 for nine days. Of 28 patients with acute nonlymphoblastic leukemia who received cumulative doses of 45 to 49 mg/m2, seven patients (25%) achieved complete remission. Four of these remissions occurred in a subset of ten patients previously resistant to two or more induction attempts with conventional chemotherapy. There were no remissions in three patients with secondary leukemia or in seven patients with acute lymphoblastic leukemia. Reversible hypotension, fluid retention, diarrhea, and tumor lysis syndrome were the major toxic effects of this treatment. Our results indicate that homoharringtonine is an effective new drug for the treatment of acute nonlymphoblastic leukemia and that this drug does not share cross-resistance with conventional antileukemic agents. The recommended dose is 5 mg/m2/d administered by continuous infusion for nine days.
高三尖杉酯碱（HHT）是一种最初在中国分离出来的新型植物生物碱。初步研究表明其在几种肿瘤疾病中具有抗肿瘤活性。我们对49例复发或难治性急性白血病患者采用持续静脉输注递增剂量的高三尖杉酯碱进行治疗。研究了三个剂量水平：5mg/m² 持续7天、7mg/m² 持续7天以及5mg/m² 持续9天。在接受累积剂量为45至49mg/m² 的28例急性非淋巴细胞白血病患者中，7例（25%）实现完全缓解。其中4例缓解发生在之前对两种或更多次传统化疗诱导尝试耐药的10例患者亚组中。3例继发性白血病患者和7例急性淋巴细胞白血病患者均未出现缓解。可逆性低血压、液体潴留、腹泻和肿瘤溶解综合征是该治疗的主要毒副作用。我们的结果表明，高三尖杉酯碱是治疗急性非淋巴细胞白血病的一种有效新药，且该药物与传统抗白血病药物不存在交叉耐药性。推荐剂量为5mg/m²/天，持续静脉输注9天。
