Chlorozotocin, 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose, an antitumor agent with modified bone marrow toxicity

Abstract

Chlorozotocin, 2-(3-(2-chloroethyl)-3-nitrosoureido)-D-glucopyranose, is a newly synthesized, water-soluble nitrosourea antitumor agent that is active against L1210 leukemia in mice. A 701% and a 401% increase in life-span were attained with a dose that was lethal to 10% of the animals (15 to 20 mg/kg, i.p.) in mice treated on Day 2 or Day 6 of L1210 tumor growth, respectivley. Sixity % of Day 2-treated mice and 30% of Day 6-treated mice survived for 90 days. At the maximally effective dose against L1210, chlorozotocin produced no significant depression in normal bone marrow DNA synthesis nor in peripheral neutrophil count, in contrast to a sustained greater than 90% inhibition in L1210 ascites cell DNA synthesis. If the antitumor activity and reduced bone marrow toxicity of chlorozotocin are confirmed in man the use of this compound would facilitate treatment of patients with neoplastic disease who have preexisting abnormal bone marrow function or would allow for the more effective use of a nitrosourea agent in combination with anticancer agents possessing more potent myelosuppressive properties.