Oral idarubicin as treatment for advanced myelodysplastic syndrome

The myelodysplastic syndromes (MDS) are a group of haemopoietic stem cell disorders of unknown cause, occurring predominantly in elderly patients. They have a high mortality due to deaths from complications of cytopenias or transformation to leukaemia. No effective treatment is known. Preliminary studies have identified idarubicin (IDA), an anthracycline drug that can be administered orally, as an agent with possible activity in MDS.

In a phase I-II study we administered oral IDA to 14 predominantly elderly patients (age range 40-79, median 74) with advanced forms of MDS, namely chronic myelomonocytic leukaemia (CMML) (one case), refractory anaemia with excess blasts (RAEB) (7 cases) or refractory anaemia with excess blasts in transformation (RAEB-t) (6 cases). IDA was given at a dose of 30 mg/m2 once each 2 weeks for 8 doses.

There was one complete remission (CR) and one partial response (PR), for an overall response rate of 14%. Mean survival from time of initiation of therapy was 10.0 months (+/- 8.0 months [SD]; median, 7.0 months). 5 patients developed severe side-effects, including 3 with life-threatening infections, and there were two deaths from cytopenias during the drug therapy.

In this small uncontrolled trial, the overall response rate and extent of toxicity seem similar to those reported for other forms of experimental therapy for MDS, such as low-dose cytosine arabinoside. Further evaluation of the drug's potential in this difficult condition may be warranted.