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June 28, 1965

Hydroxyurea Administered Intermittently

Author Affiliations

From the Department of Surgery, Pennsylvania Hospital, Philadelphia.

JAMA. 1965;192(13):1168-1170. doi:10.1001/jama.1965.03080260056023

THE SYNTHESIS of hydroxyurea (Hydrea) was reported in 1869 by Dresler and Stein.1 In animal studies, Rosenthal et al2 found that the compound produced anemia, severe leukopenia, and megaloblastic changes in the peripheral blood and bone marrow. Recently, this compound has been introduced into cancer chemotherapy. Tumor responses have been observed in squamous cell cancer, adenocarcinomas, melanomas, sarcomas, and chronic leukemia.3,4

The greatest limiting factor in the use of hydroxyurea has been depression of bone marrow, primarily manifested as leukopenia.3 The great majority of cancer chemotherapeutic agents (nonhormonal) produce depression in hematopoiesis. In addition to this depression, most agents produce other toxic reactions as noted by Hall.5

The incidence of toxicity with hydroxyurea is 68% when 40 mg/kg of body weight per day, the originally suggested oral dose, is given. A twofold increase in that dose produces toxic reactions in all patients.3

Each patient