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.
