Synergistic antitumor effect of cisplatin and the platinum(iv) nitroxyl complex BC118 and the development of resistance to their combined action

The efficacy of the combination treatment of P388 leukemia with cisplatin (cPt) and the platinum(IV) nitroxyl complex BC118 [e-ammine-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-bis(acetato)-b,c-dichloroplatinum(iv)] applied in low doses was found to be synergistically increased. Thus, the use of 1/10 of their LD50 cured 100% of animals. The monotherapy with these drugs used in the same doses and at the same schedules showed moderate efficacy, and no animals survived. A synergistic increase in the toxicity was not observed. The rate of the development of resistance decreases in the series cPt+BC118, cPt, and BC118. Strains resistant to cPt+BC118 and BC118 are highly sensitive to doxorubicin, etoposide, and cyclophosphane.