1,2-Diaminocyclohexane platinum derivatives of potential clinical value.
1,2-Diaminocyclohexane platinum derivatives of potential clinical value.
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具有潜在临床价值的1,2-二氨基环己烷铂衍生物。
DOI：
10.1007/978-3-642-81488-4_19
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
Turkevich,J
中科院分区：
文献类型：
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作者：
Burchenal,JH;Irani,G;Kern,K;Lokys,L;Turkevich,J
顺胺二氯铂（DDP）在临床癌症化疗中发挥着重要作用，无论是单独使用，还是更常见的与博来霉素、阿霉素、环磷酰胺、长春地西或阿拉伯糖胞嘧啶（阿拉- c）衍生物联合使用。通过这些组合，许多研究者报道了睾丸、头颈部、阴茎、子宫颈、膀胱、肺、食道和卵巢的生殖细胞肿瘤的活性[1,7]。它在白血病和淋巴瘤中的应用要少得多。不幸的是，肾毒性和严重的恶心和呕吐限制了它的使用，因此人们正在寻找毒性更小、抗肿瘤效果更好、活性范围更广的化合物，包括白血病和淋巴瘤，特别是那些对DDP缺乏交叉耐药性的化合物。正如先前各种研究者所报道的[9,13],1,2-二氨基环己烷铂衍生物似乎符合这些标准。在实验动物中，肾毒性似乎没有限制[10]，在小鼠白血病中，对DDP没有交叉耐药[2,3]。1,2-二氨基环己烷铂的二氯、丙二酸和羧基邻苯二酸衍生物在实验中显示出高度的抗肿瘤效果[9,13]，与ara-C衍生物、阿霉素、去甲基罂粟叶毒素乙基葡萄糖苷（VP-16）[2]和环磷酰胺具有明显的协同作用，特别是与各种核糖核苷酸还原酶抑制剂如羟基脲、胍唑和MAIQ-1[6]联合使用时。临床上，HILL等人（[8]）报道了丙二酸酯衍生物在急性白血病中具有临床活性，RIBAUD等人（[8]）报道了丙二酸酯衍生物在临床上对DDP产生耐药性的患者中具有缓解作用。
Cisdiamminodichloroplatinum (DDP) has assumed an important role in clinical cancer chemotherapy either alone or, more often, in combination with bleomycin, adriamycin, Cytoxan (cyclophosphamide), vindesine, or the arabinosylcytosine (ara-C) derivatives. With these combinations, many investigators have reported on activity in germ cell tumors of the testis, carcinoma of the head and neck, penis, cervix, bladder, lung, esophagus, and ovary [1,7]. It has been used much less in the leukemias and lymphomas. Unfortunately, renal toxicity and severe nausea and vomiting have limited its usefulness, and compounds with less toxicity, greater antitumor effectiveness, and a broader spectrum of activity, including the leukemias and lymphomas, are being sought, particularly those lacking cross-resistance to DDP. As previously reported by various investigators [9, 13], the 1,2-diaminocyclohexane platinum derivatives seem to fit these criteria. In the experimental animal renal toxicity does not appear to be limiting [10], and in mouse leukemia there is no cross-resistance to DDP [2, 3]. The dichloro, malonato, and carboxyphthalato derivatives of 1,2-diaminocyclohexane platinum experimentally have shown a high degree of antitumor effectiveness [9, 13], marked synergism with ara-C derivatives, adriamycin, demethylepipodophyllotoxin ethylidene glucoside (VP-16) [2], and with cyclophosphamide, particularly in combination with various ribonucleotide reductase inhibitors such as hydroxyurea, guanazole, and MAIQ-1 [6]. Clinically, the malonato derivative has been reported by HILL et al. [8] to be clinically active in the acute leukemias, and by RIBAUD et al. [11] to produce remissions in patients whose disease had become clinically resistant to DDP.