Improved Therapeutic Index of Cisplatin by Procaine Hydrochloride

The local anesthetic procaine hydrochloride (P.HC1) had little effect on the sensitivity of P388 leukemic cells to cisplatin (DDP) in vitro, but the simultaneous administration of DDP and P.HC1 (40 mg/kg) to BDF, mice produced 50 % lethal dose (LDJQ) and 90 % lethal dose (LD^) values approximately two times higher than those observed with DDP alone. DDP-P.HC1 diluted in water and administered intraperito-neally (IP) on day 1 and on days 1 and 5 to BDF, mice bearing P388 leukemic cells produced 33 % and 50 % cure rates, respectively, at the maximum tolerated dose (16 mg/kg for the single administration and 10 mg/kg given on days 1 and 5). In contrast, under the same conditions, the cure rates obtained with DDP alone (10 mg/kg for the single administration and 8 mg/kg given on days 1 and 5) were 17 % and 9%, respectively. Protection from DDP nephrotoxicity seems to be the explana