Evaluation of antitumor activity of 1-beta-D-arabinofuranosyl-2-amino-1,4(2H)-4-iminopyrimidine in murine tumors.

1-beta-D-Arabinofuranosyl-2-amino-1,4(2H)-4-iminopyrimidine (ara-AIPy), a new deaminase-resistant analog of cytarabine, exhibited extremely potent antitumor activity against P388 leukemia [400 mg/kg on Days 1-5; increase in life span (ILS), 211%] and significant inhibition against Lewis lung carcinoma (inhibition of tumor weight, 68%) and mammary adenocarcinoma 755 (inhibition of tumor weight, 82%). Schedule-dependency studies indicate that this drug, unlike cytarabine, was effective irrespective of its treatment schedules. The drug exhibited therapeutic efficacy against established P388 tumor transplants (400 mg/kg on Days 3-7; ILS, 131%) and inhibited the tumor growth effectively even when administered as a single dose on Day 1 by both ip (2000 mg/kg; ILS, 150%) and iv (500 mg/kg; ILS, 68%) routes. Ara-AIPy was most effective when administered on Days 1, 3, 5, 7, and 9 after tumor transplantation (400 mg/kg; ILS, 210%, with 50% of animals 60-day survivors). Ara-AIPy inhibited the growth of L1210 leukemia when both the tumor transplantation and the drug treatment were administered by iv route (500 mg/kg on Days 1, 5, and 9; ILS, 181%). The routes of administration of ara-AIPy experiments showed that the drug was effective by both ip and iv routes of administration; however, better therapeutic values were obtained by ip schedules. These studies demonstrate that ara-AIPy exhibits highly significant and broad-spectrum antitumor activity against a variety of experimental animal tumor models and suggest a possible future role for this drug in the treatment of human neoplasia.