Oral isobutyramide therapy in patients with thalassemia intermedia: Results of a phase II open study

A pilot phase II open study on 12 patients with thalassemia intermedia (7 m en, 5 women; age 31 +/- 2.0 years SE) treated with oral isobutyramide, a de rivative of butyric acid (150 mg/kg body wt/day), was performed in order to evaluate the effect of this compound in stimulating hemoglobin F (HbF) pro duction. No patient underwent blood transfusion in the 1-year time frame pr ior to the study. Nine patients were splenectomized. Safety was monitored b y clinical and laboratory tests. Efficacy was assessed in terms of the non- alpha/alpha globin chain biosynthetic ratio and the percentage increase of HbF. The study design consisted of a screening phase, a treatment phase of 28 days, and a posttreatment follow-up of 28 days. All patients completed t he study. Compliance to treatment was 100%. No drug-related adverse event w as recorded. We observed little or no increase in the non-alpha/alpha ratio in the majority of patients. Six patients showed a percentage increase of HbF at the end of treatment and in 5 of those 6 further increases at the en d of the follow-up period were observed. The change in percentage of HbF ov er time was close to significance both in the treatment period (P = 0.06) a nd in the follow-up period (P = 0.08). These results indicate that butyrate derivatives can stimulate fetal hemoglobin in patients with intermediate t halassemia. Testing of the effects of different schedules of administration of isobutyramide will be required in order to determine the optimal use of this compound in the treatment of the beta-thalassemia syndromes. (C) 2000 Academic Press.