Time-dependent influence of procaine hydrochloride on cisplatin antitumor activity in p388 tumor bearing mice

In previous papers (1,2) we demonstrated that procaine hydrochloride may in crease the therapeutic index of cisplatin by an improvement of its antitumo r activity and a reduction of its nephrotoxicity. In the present study we i nvestigated the relationship between the antitumor activity obtained by cis platin associated with procaine hydrochloride and the relative time of admi nistration of these two agents. When procaine hydrochloride (40 mg/Kg body wt) was administered 30 or 120 minutes before cisplatin (16 mg/kg) diluted in normal saline (i.e. clinical condition) it increased, although not signi ficantly, its percent increase in life span (%ILS) and cure rate (%ILS: +29 2 and +217 vs +150; cute rate: 46.2% and 42.3% vs 23%, respectively), compa red to cisplatin alone treatment. These results became statistically signif icant when procaine hydrochloride was given either simultaneously with cisp latin ol 30 and 120 minutes thereafter (%ILS: >400 vs +150; cure rate: 65.4 % 73.1% and 68% vs 23%, respectively). In conclusion procaine hydrochloride increased the antitumor activity of cisplatin independently from its timin g of administration, although it seemed to be a better potentiating agent w hen administered after cisplatin.