Experimental chemotherapy with 5-arylpyrimidine antifolates: Further studies on toxicity and the responsiveness of ascitic, solid, and intracranial sarcoma 180 to DDMP and DDMP with citrovorum factor.

Multiple-dose toxicity of the 5-arylpyrimidine DDMP showed marked seasonal variation and sex dependence in BD2F1 mice. Considerable therapeutic activity against the ascitic, solid, and intracranial forms of Sarcoma 180 was demonstrated. Antitumor effects were highly schedule and dose dependent at a limited number of doses between 16 and 40 mg/kg. Antitumor activity (increase in lifespan) was approximately twofold greater against the ascitic tumor compared to the intracranial tumor at each dose level. The use of citrovorum factor rescue appeared to improve the therapeutic index of DDMP against intracranial Sarcoma 180 on specific multiple-dose schedules. Citrovorum factor rescue did not result in a greater initial antitumor effect of DDMP against the solid Sarcoma 180, but the effect was maintained for a longer period of time by allowing an increase in the number of doses which could be administered without toxicity.