| Abstract: | cis-Dichlorodiammineplatinum(II) (cis-platinum) and 40 of its analogs were evaluated for antitumor activity in BDF1 mice implanted ip with 10(6) L1210 leukemia cells. Several of these analogs were also evaluated for their ability to cause elevation in BUN and to produce leukopenia in normal BDF1 mice. In 11 experiments, cis-platinum given on Day 1 or Days 1--9 after implant produced T/C (treated/control) values between 164% and 214% and 157% and 285% respectively. On the basis of single experiments, 13 analogs were judged to be comparable to cis-platinum in that they produced T/C values greater than or equal to 167% after a single dose or greater than or equal to 200% after daily doses for 9 days. These active compounds included various substituted amine derivatives of dichloroplatinum(II), malonatoplatinum(II), aquasulfatoplatinum(II), and chloroacetatoplatinum(II) and derivatives of dihydroxydichloroplatinum(IV). Twelve of these active analogs and cis-platinum were evaluated for toxicity at doses ranging from near the optimal therapeutic dose to greater than or equal to the LD50. Only five of the 12 analogs and cis-platinum caused an increase in BUN to greater than 30 mg/100 ml, while eight of the analogs produced leukopenia comparable in incidence and severity to that produced by cis-platinum. |
