Therapeutic potentiation of combined cis-dichlorodiammineplatinum (II) and irradiation by ICRF-159

The effect of fractionated ICRF-159 (25 mg/kg, q3hx4) pretreatment on the antitumor activity of cis DDP + irradiation combinations has been evaluated using the Lewis lung tumor. All three agents given alone as single treatments result in transient interruption of proliferative activity with only slight to moderate alterations of tumor growth. Fractionated ICRF-159 treatment, while eliciting low cytotoxicity, results in a partial cytokinetic redistribution of tumor cells enhancing subsequent radiotherapy and chemotherapy with cis DDP. For cis DDP-radiation combinations, where cis DDP precedes irradiation, increasing the intertreatment time from 6 h to 24 h results in synergistic interactions and increased treatment efficacy. When cis DDP-radiation combinations followed fractionated ICRF-159, regression was greatly enhanced suggesting that relatively non-cytotoxic agents may be used to sensitize low growth fraction, resistant tumors to subsequent combined-mode therapy