Kantarjian H M, Talpaz M, Santini V, Murgo A, Cheson B, O'Brien S M
Department of Leukemia, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2001 Sep 15;92(6):1591-605. doi: 10.1002/1097-0142(20010915)92:6<1591::aid-cncr1485>3.0.co;2-u.
Cephalotoxine esters, including homoharringtonine (HHT), have shown encouraging activity in leukemia in initial studies in China and in later studies in the U.S.
The authors conducted a review of the literature to examine the studies pertinent to HHT in relation to preclinical studies and Phase I-II trials in patients with hematologic malignancies and solid tumors.
HHT and analogues appear to induce differentiation and apoptosis. Studies from China reported high response rates in patients with leukemia. Trials in the U.S. using short HHT infusions (3-4 mg/m(2) daily for 5 days) resulted in a high incidence of cardiovascular complications that were reduced using continuous infusion schedules of 3-7 mg/m(2) daily for 5-7 days initially, and later lower dose schedules of 2.5 mg/m(2) daily for 7-14 days. Results in solid tumors were negative. However encouraging results were reported in patients with acute myeloid leukemia, myelodysplastic syndrome, acute promyelocytic leukemia, and, most important, chronic myeloid leukemia (CML). In CML patients, HHT has been investigated alone and in combination with interferon-alpha and low-dose cytarabine in late and early chronic phases, with positive results. Additional areas of interest include the potential use of HHT for the treatment of central nervous system leukemia, polycythemia vera, and other nonmalignant conditions such as malaria. New semisynthetic preparations and HHT derivatives that bypass multidrug resistance may improve the efficacy and toxicity profiles, and broaden the range of antitumor efficacy.
HHT and its derivatives appear to have promising activity in hematologic malignancies, a finding that needs to be pursued.
包括高三尖杉酯碱（HHT）在内的头霉素酯在中国的初步研究以及美国后来的研究中均显示出对白血病有令人鼓舞的活性。
作者对文献进行了综述，以研究与HHT相关的血液系统恶性肿瘤和实体瘤患者的临床前研究及I-II期试验。
HHT及其类似物似乎可诱导分化和凋亡。中国的研究报告白血病患者的缓解率很高。美国使用短时间HHT输注（每日3-4mg/m²，共5天）的试验导致心血管并发症发生率很高，最初采用每日3-7mg/m²连续输注5-7天的方案后并发症减少，后来采用每日2.5mg/m²连续输注7-14天的较低剂量方案。实体瘤的研究结果为阴性。然而，在急性髓性白血病、骨髓增生异常综合征、急性早幼粒细胞白血病患者中报告了令人鼓舞的结果，最重要的是在慢性髓性白血病（CML）患者中。在CML患者中，已对HHT单独以及与α干扰素和小剂量阿糖胞苷联合用于慢性期晚期和早期进行了研究，结果呈阳性。其他感兴趣的领域包括HHT在治疗中枢神经系统白血病、真性红细胞增多症以及疟疾等其他非恶性疾病方面的潜在用途。新的半合成制剂和绕过多药耐药性的HHT衍生物可能会改善疗效和毒性特征，并拓宽抗肿瘤疗效范围。
HHT及其衍生物在血液系统恶性肿瘤中似乎具有有前景的活性，这一发现有待进一步研究。
