The overall objective of ongoing research is to develop as a new marketable pharmaceutical product, a platinum based antitumor agent which would have significant advantages over the commercially very successful drug, cisplatin. Advantages sought include but are not limited to overcoming the dose limiting nephro- and gastrointestinal toxicities of cisplatin. Of especial importance is the need to develop a drug which would have therapeutic value to patients whose tumors have developed resistance to cisplatin therapy. During the Phase I research, a series of new platinum complexes related to the clinically tested complex 4-carboxyphthalato(1,2-diaminocyclohexane)platinum (NSC 271674) were synthesized and screened against L1210 leukemia. Modifications incorporated included using substituted catechols and salicylic acids in place of the phthalic acid ligand. One such compound, 5-carboxysalicylato(1,2-diaminocyclohexane)platinum (NSC 377217D), was screened by NCI and shown in repeated testing to have T/C percent values in excess of 300, including as high as 4/6 cures. Phase II research will focus on further development of this and other compounds including alternate synthetic approaches, scale up, and additional screening and toxicity testing. At the end of the Phase II period much of the data required to file an IND with the FDA will be available.
