Antitumor Activity of Improsulfan by the Fractionated Dose Schedule on Rat Ascites Tumors

The antitumor activity of improsulfan was examined with respect to an increase in the lifespan of rats bearing ascites tumors when a relatively low dose (5 and 20 mg/kg) was given intraperitoneally in two equal fractions and in a single dose. The fractionated dose schedule, even when given in a time interval of over 24 hr, was more effective against tumors sensitive to alkylating agents, Yoshida sarcoma and AH-272. Against other tumors, the fractionated dose schedule was more effective only when given in an interval of within 3 hr or was equally effective at all of the intervals tested as the single dose schedule. The toxicity of improsulfan to normal healthy rats was severer in a single dose than in two equal fractions of the same total dose, 150 mg/kg. Therapeutic synergism was observed against Yoshida sarcoma when intraperitoneal administration of improsulfan and oral administration of cyclophosphamide were made simultaneously. The pharmacokinetic process in tissue concentrations of alkylating agents like that presumed in the fractionated dose schedule of improsulfan may occur by this combination.