STABILIZATION OF THE ANTICANCER DRUG DACH-PT--NSC 271674

络合物4-羧基邻苯二甲酸（1，2-二氨基环己烷）铂（NSC 271674; DACH-Pt）由提议的研究者之一发明，已经经历了 在纪念斯隆-凯特琳癌症中心进行的有限临床试验， 约克。 作为顺铂的替代疗法，它已经证明 显著降低毒性并增强对抗肿瘤药物的活性。 顺铂在动物研究中，结果在临床中得到证实。 严重 对DACH-Pt治疗有反应的I期和II期预治疗患者 包括肺、鼻咽、胃、卵巢和膀胱 癌的 肾和胃肠道毒性，主要副作用 顺铂，是最小的。 尽管该复合物具有出色的治疗特性， 纯化困难和固有的不稳定性，导致 水解解离，实际上已经停止了进一步的临床研究。 评估对于将其发展成为一种商业上可获得的 抗癌药 提议的研究人员已经解决了所有的净化问题， 重复制备大量原料药进行分析 临床使用规范。 现在建议尝试 通过改变温度、pH值、缓冲液浓度等来稳定药物， 为了获得最佳条件， 具有可接受的稳定特性，同时保持其上级 治疗特性。 成功稳定足以用于配制的DACH-Pt将导致 一种具有很强商业潜力的药物产品。

The complex 4-carboxyphthalato(1,2-diaminocyclohexane)platinum (NSC 271674; DACH-Pt) invented by one of the proposed INvestigators, has undergone limited clinical trials at Memorial Sloan-Kettering Cancer Center, New York. Designed as an alternative therapy to cisplatin, it has demonstrated substantially reduced toxicity and enhanced activity in tumors resistant to cisplatin in animal studies, results confirmed in the clinic. Heavily pretreated Phase I and Phase II patients responding to DACH-Pt therapy included those with lung, nasopharyngeal, gastric, ovarian, and bladder cancers. Renal and gastrointestinal toxicity, the major side effects of cisplatin, were minimal. Even though the complex possesses outstanding therapeutic properties, difficulties in purification and an inherent instability, resulting in hydrolytic dissociation, has virtually halted the further clinical evaluation essential for its development into a commercially available anticancer drug. The proposing investigators have solved all purification problems and have repeatedly prepared bulk quantities of the drug material to analytical specifications for clinical use. It is now proposed to attempt to stabilize the drug by varying temperature, pH, buffer concentration, etc., in an effort to obtain the optimum conditions in which the complex will have acceptable stability characteristics while retaining its superior therapeutic properties. Successful stabilization of DACH-Pt sufficient for formulation will lead to a drug product with very strong commercial potential.