Metabolic and Therapeutic Effects of Hydroxyurea in Chronic Myeloid Leukemia

Abstract

Hydroxyurea (Hydrea) is a compound currently employed in clinical trials in malignant disease. It has produced bone marrow suppression, megaloblastosis, and antitumor effects in animals and man. Hydroxyurea was first synthesized by Dresler and Stein in 1869.¹Its empirical formula is CH⁴N²O²and its structural formula is shown in Fig 1. Hydroxyurea was employed in biological studies in 1928 by Rosenthal and co-workers who demonstratedthe development of anemia and megaloblastosis in rabbits during treatment with large doses. They also observed a depression of leukocyte formation in the bone marrow (Table 1).²Further biological studies were reported in 1958,³and in 1960 antitumor activity was reported in animal screening studies.⁴ Hydroxyurea has antitumor activity against transplantable L1210 leukemia in mice and against L1210 strains that were resistant to methotrexate (Amethopterin), 2-amino-6-purinethiol or 8-aza-guanine. It was also active against the solid tumor