Schweitzer V G, Rarey K E, Dolan D F, Abrams G, Litterst C J, Sheridan C
Otolaryngol Head Neck Surg. 1986 Apr;94(4):458-70. doi: 10.1177/019459988609400410.
Cis-diamminedichloroplatinum (cisplatin), a divalent platinum compound and cell-cycle nonspecific chemotherapeutic agent, produces a permanent high-frequency sensorineural hearing loss and a dose-related cumulative renal insufficiency with tubular necrosis and interstitial nephritis. Synthetic platinum analogs are presently being tested to identify an analog with greater antitumor activity, but less ototoxicity and nephrotoxicity than cisplatin. The objectives of this study were to analyze the potential cochlear and nephrotoxic effects of two synthetic platinum analogs presently in phases I and II of clinical trials, CBDCA [JM-8 or cis-diammine, 1,1-cyclobutane dicarboxylato (2)-0,0(1)-platinum (NSC-241240)] and CHIP [JM-9 or cis-dichloro-trans-dihydroxybisisopropylamine platinum IV (NSC-256927)]. Cytocochleography, auditory brain-stem evoked response (ABR), double-blind light microscopy of renal tissues, and gamma emission analysis of 195mpt localization in viscera and inner ear were employed in the evaluation of cisplatin and platinum analogs (JM-8 and JM-9) in adult guinea pigs. Final results indicate that the investigational chemotherapeutic analogs CBDCA (JM-8) and CHIP (JM-9) do not produce the ototoxicity and nephrotoxicity characteristic of cisplatin. Furthermore, these findings demonstrate 195mpt localization in the vestibular labyrinth and confirm previous platinum distribution studies in the organ of Corti and stria vascularis tissues.
顺二氯二氨铂（顺铂）是一种二价铂化合物，属于细胞周期非特异性化疗药物，可导致永久性高频感音神经性听力损失以及与剂量相关的累积性肾功能不全，并伴有肾小管坏死和间质性肾炎。目前正在对合成铂类似物进行测试，以确定一种抗肿瘤活性更高，但耳毒性和肾毒性比顺铂更低的类似物。本研究的目的是分析两种目前正处于临床试验I期和II期的合成铂类似物，即卡铂[JM - 8或顺二氨，1,1 - 环丁烷二羧酸根（2）- 0,0（1）-铂（NSC - 241240）]和四羟基二异丙胺二氯铂（IV）[JM - 9或顺二氯 - 反二羟基双异丙胺铂（IV）（NSC - 256927）]的潜在耳蜗和肾毒性作用。在对成年豚鼠体内的顺铂和铂类似物（JM - 8和JM - 9）进行评估时，采用了细胞耳蜗造影术、听性脑干诱发电位（ABR）、肾组织双盲光学显微镜检查以及对195mpt在内脏和内耳中的定位进行γ发射分析。最终结果表明，受试化疗类似物卡铂（JM - 8）和四羟基二异丙胺二氯铂（IV）（JM - 9）不会产生顺铂特有的耳毒性和肾毒性。此外，这些研究结果证明了195mpt在前庭迷路中的定位，并证实了先前在柯蒂氏器和血管纹组织中的铂分布研究。
