Laadem A, Cvitkovic E
18-20, rue Pasteur, 94278 Kremlin-Bicêtre Cedex.
Bull Cancer. 2001 Aug;88 Spec No:S9-13.
Around 3,000 cisplatin analogues have been synthetised over the past 30 years but only half a dozen are presently in clinical development, while only two (cisplatin and carboplatin) have been available prior to the recent European registration of oxaliplatin. Oxaliplatin is a new platinum salt belonging to the DACH (diaminocyclohexane) platinum family, and is the only such cisplatin analogue that has entered clinical development and achieved approval for marketing. During its development, oxaliplatin has aroused lively interest due, firstly, to its in vitro and in vivo antitumoral activity, especially in cisplatin-resistant models and cell lines expressing resistance genes, and, secondly, to its good clinical tolerance, the absence of renal or auditory toxicity being combined with a low hematotoxicity. Combined with other antitumoral agent cytotoxic agents (5FU, raltitrexed, irinotecan or cisplatin), oxaliplatin produces an additive and often synergistic cytotoxic effect. The oxaliplatin-5FU +/- FA combination is now well established in metastatic colorectal cancer. Regarding its particular cytotoxic characteristics and its activity in mismatch repair deficient cells (which are resistant to cisplatin and carboplatin), oxaliplatin is shows potential in a large variety of solid tumor types, notably in association with other cytotoxic agents, thus opening the path to a wider range of indications.
在过去30年里已合成了约3000种顺铂类似物，但目前只有六种处于临床开发阶段，而在奥沙利铂最近在欧洲获批上市之前，只有两种（顺铂和卡铂）已可供使用。奥沙利铂是一种属于二氨基环己烷（DACH）铂类家族的新型铂盐，是唯一进入临床开发并获得上市批准的此类顺铂类似物。在其研发过程中，奥沙利铂引起了广泛关注，首先是因其在体外和体内的抗肿瘤活性，特别是在顺铂耐药模型和表达耐药基因的细胞系中，其次是因其良好的临床耐受性，不存在肾毒性或耳毒性，且血液毒性较低。与其他抗肿瘤细胞毒性药物（5-氟尿嘧啶、雷替曲塞、伊立替康或顺铂）联合使用时，奥沙利铂会产生相加且往往是协同的细胞毒性作用。奥沙利铂-5-氟尿嘧啶+/-亚叶酸联合方案目前在转移性结直肠癌中已得到充分确立。鉴于其特殊的细胞毒性特征及其在错配修复缺陷细胞（对顺铂和卡铂耐药）中的活性，奥沙利铂在多种实体瘤类型中显示出潜力，特别是与其他细胞毒性药物联合使用时，从而为更广泛的适应症开辟了道路。
