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

The Complex 4-carboxyphthalato(1，2-diaminocyclohexane)platinum(国家安全委员会271674； DACH-PT)由一位拟议的调查人员发明，已经经历了 在纽约纪念斯隆-凯特琳癌症中心进行的有限临床试验 约克市。作为顺铂的替代疗法，它已经证明 显著降低毒性和增强抗药性肿瘤的活性 顺铂在动物实验中，结果在临床上得到证实。沉重地 对DACH-铂治疗有反应的前治疗I期和II期患者 包括肺、鼻咽、胃、卵巢和膀胱癌 癌症。肾和胃肠道毒性，主要副作用 顺铂，为最低限度。 尽管该复合体具有出色的治疗特性， 提纯困难和固有的不稳定性，导致 水解性解离，实际上已经停止了进一步的临床 评估对于将其发展为商业可用的 抗癌药物。 提出建议的调查人员已经解决了所有的净化问题，并 反复制备大批量的药物材料进行分析 临床使用规范。现在有人提议尝试 通过改变温度、pH、缓冲液浓度等来稳定药物， 在努力获得最佳条件下，综合体将 具有可接受的稳定性特性，同时保持其优势 治疗特性。 DACH-铂的成功稳定足以用于制剂将导致 具有很强商业潜力的药品。

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.