Because DBD is hydrolyzed to DAG in situ, it is not immediately obvious why administration of DBD would be preferred to DAG. In the United States, DBD is administered orally and DAG is administered intravenously. Because DBD is readily absorbed in the gastrointestinal tract and has a long plasma half-life, this difference in route of administration is important clinically.5 When administered in vitro, DAG produces cell kill only after extended periods of exposure.21,22 Thus, daily oral administration of DBD assures that relatively constant levels of DAG are present in situ for sufficiently long periods of time to kill tumor cells and to prevent the repair of cell damage caused by DAG.
Because of some variability in DBD absorption in patients, due to dietary and other factors, Bellet, et al.,6 treated metastatic melanoma patients with DBD doses sufficient to cause actual hematological toxicity. Patients were treated with daily doses of 100 mg/sq m until the white blood cell (WBC) count or platelet count fell to 50% of pretreatment levels; this level of myelotoxicity was tolerable but dose-limiting. In the study reported here, we used this same treatment protocol in a Phase II study of patients harboring recurrent primary malignant brain tumors who had failed to respond to previous therapies.
We thank the physicians in Northern California, and especially at the Kaiser-Permanente Medical Centers of the Greater Bay Area, for referring patients to our service. We thank Irene Asturias for typing the manuscript in draft.
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Dibromoducitol was supplied by the Division of Cancer Treatment, National Cancer Institute, Bethesda, Maryland.
This work was supported in part by NIH Program Project Grant CA 13525.