ANTITUMOR-ACTIVITY AND NEPHROTOXICITY OF A NOVEL PLATINUM COMPLEX, PHENYLPHOSPHINO)PROPANE](TRANS-1-DACH)PLATINUM(II) DINITRATE

We have developed a new class of platinum complex: [Pt(trans-l-dach)(1 ,3-bis(phosphino)propane)] dinitrate (KHPC-001) with potent antitumor activity and low nephrotoxicity, confirmed in vitro and compared in vi vo with cisplatin. KHPC-001 ol cisplatin was intraperitoneally injecte d on days 1, 5, and 9 into P388-bearing mice and the antitumor effects were compared In vitro cytotoxicity, Pt accumulation, and DNA cross-l ink index were measured in P388 and LLC-PK1 cells after treatment with KHPC-001 or cisplatin. Twenty mg/kg (below one-tenth of LD50) of KHPC -001 had stronger antitumor effects than 2 mg/kg (about one-fifth of L D50) of cisplatin and cured 2 out of 6 mice without any toxicity. Whil e the cytotoxicity of KHPC-001 and cisplatin were similar on P388 mous e leukemia cells, this new compound was much less cytotoxic to a kidne y-derived line, LLC-PK1. This lower toxicity on the kidney cells was b ased on its low accumulation, causing less DNA crosslinking. KHPC-001 is a unique third-generation platinum complex with potent antitumor ac tivity and low nephrotoxicity.