Jehn U, Heinemann V
Department of Hematology/Oncology, University of Munich, FRG.
Anticancer Res. 1991 Mar-Apr;11(2):705-11.
Several new cytostatic drugs have entered clinical phase I-II studies for the treatment of leukemia: the most promising are pyrimidine analogs such as 5-aza-cytidine, 5-aza-2'-deoxycytidine, 5-aza-cytosine arabinoside, and 2',2'-difluorodeoxycytidine. Fludarabine, a fluorinated purine analog, appears to be active in CLL and multiple myeloma. Deoxycoformycin, an adenosine analog, showed good activity in the treatment of hairy cell leukemia and T-cell neoplasias. 2-chloro-deoxyadenosine has recently been introduced into the treatment of CLL and hairy-cell leukemia refractory to deoxycoformicin. Tiazofurin, an antimetabolite which interferes with nicotine-adenine-dinucleotide (NAD) metabolism, has been applied in CML blast crisis. Other agents include 13-cis retinoic acid and 1, 25-dihydroxy vitamin D3 as differentiation inducers, and homoharringtonine, an alkylating agent which is widely used for ANLL treatment in China. Among new anthracyclines, aclarubicin, idarubicin, THP-adriamycin and fluoro-adriamycin should be mentioned. Mitoxantrone, a substituted anthraquinone, has successfully been applied in the treatment of relapsed and refractory ANLL. Amsacrine (m-AMSA), finally, is a synthetic aminoacridine which intercalates into DNA and inhibits DNA topoisomerase II. m-AMSA is not cross-resistant to anthracyclines and has been particularly active in ANLL treatment. Studies using m-AMSA alone or in combination revealed comparable results to anthracycline--containing regimens. Cardiotoxicity of the anthracycline congestive type has not been observed with m-AMSA. The EORTC Leukemia Cooperative Group has successfully used m-AMSA in several trials prepositioning this drug stepwise: from relapsed and refractory ANLL, into intensive maintenance treatment during first remission in ANLL, and, still on-going, into intensive consolidation.
几种新型细胞毒性药物已进入治疗白血病的临床I-II期研究：最有前景的是嘧啶类似物，如5-氮杂胞苷、5-氮杂-2'-脱氧胞苷、5-氮杂胞嘧啶阿拉伯糖苷和2',2'-二氟脱氧胞苷。氟达拉滨，一种氟化嘌呤类似物，似乎对慢性淋巴细胞白血病（CLL）和多发性骨髓瘤有活性。脱氧助间型霉素，一种腺苷类似物，在治疗毛细胞白血病和T细胞肿瘤方面显示出良好的活性。2-氯脱氧腺苷最近已被用于治疗对脱氧助间型霉素耐药的CLL和毛细胞白血病。替唑呋林，一种干扰烟酰胺腺嘌呤二核苷酸（NAD）代谢的抗代谢物，已应用于慢性粒细胞白血病急变期。其他药物包括13-顺式维甲酸和1,25-二羟基维生素D3作为分化诱导剂，以及高三尖杉酯碱，一种在中国广泛用于急性非淋巴细胞白血病（ANLL）治疗的烷化剂。在新型蒽环类药物中，应提及阿克拉霉素、伊达比星、吡柔比星和氟柔比星。米托蒽醌，一种取代蒽醌，已成功应用于复发和难治性ANLL的治疗。最后，安吖啶（m-AMSA）是一种合成氨基吖啶，可嵌入DNA并抑制DNA拓扑异构酶II。m-AMSA与蒽环类药物无交叉耐药性，在ANLL治疗中特别有效。单独使用或联合使用m-AMSA的研究显示出与含蒽环类药物方案相当的结果。未观察到m-AMSA引起蒽环类充血型心脏毒性。欧洲癌症研究与治疗组织（EORTC）白血病协作组已在多项试验中成功使用m-AMSA，逐步将该药物定位：从复发和难治性ANLL，到ANLL首次缓解期的强化维持治疗，并且仍在进行的，到强化巩固治疗。
