Between December 1, 1995, through November 30, 1996, we continued accrual to J9446, Phase I study of sodium phenylbutyrate in myelodysplasia and acute myeloid leukemia. 18 patients were accrued during this period. Of these, 8 were treated in the GCRC. The drug has been administered as a 7 day IV continuous infusion, repeated on a 28 day schedule. We identified dose-limiting toxicity of phenylbutyrate at 500 mg/kg/day by intravenous continuous infusion; this toxicity was also present at 440 mg/kg/day. Thus, 375 mg/kg/day was selected as the dose for further development. Phenylbutyrate showed significant activity in increasing neutrophil and platelet counts, and reducing peripheral blast counts in several patients. Hemoglobin F production was increased in patients who had measurable hemoglobin F before entering the protocol. We have now begun the study of 375 mg/kg/day given as an IV continuous infusion as an outpatient for prolonged infusions (7 days on/ 7 days off; 3 weeks on/one week off). We hope to combine this drug with retinoids in the future. We do not anticipate further use of the inpatient GCRC for this study.
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