ACTIVITY OF A NOVEL ANTHRACENEDIONE, 1,4-DIHYDROXY-5,8-BIS[[[2-[(2-HYDROXYETHYL)AMINO]ETHYL]AMINO]]-9,10-ANTHRACENEDIONE DIHYDROCHLORIDE, AGAINST EXPERIMENTAL-TUMORS IN MICE

Abstract

1,4-Dihydroxy-5,8-bis{({2-[(2-hydroxyethyl)amino]ethyl}amino)}-9,10-anthracenedione dihydrochloride (CL 232315; NSC 301739D), a representative of a new chemical class of compounds with antineoplastic properties, was evaluated for antitumor activity in experimental mouse tumor systems. The compound produced significant increases in life span (ILS) and long-term survivors when tested against the P388 and L1210 leukemias and the solid neoplasms B16 melanoma and colon tumor 26. The optimal treatment regimens resulted in a 173 to > 200% ILS and 20-80% 60 day survivors in mice with P388 leukemia, a 205% ILS with 55% 60 day survivors in mice with L1210 leukemia, and an ILS of > 300% with 80% 90 day survivors in mice with B16 melanoma. In contrast to adriamycin, CL 232315 was active against the i.v. implanted L1210 leukemia and demonstrated moderate activity against P388/Adria, a subline of P388 resistant to adriamycin. The compound was ineffective when tested against the Lewis lung carcinoma and the Ridgway osteogenic sarcoma. CL 232315 was active i.p., s.c., and i.v., but p.o. [per oral] activity was not demonstrated. Schedule dependency was not observed when the compound was administered once daily for 9 days, once every 4 days, or as a single dose.