New Agent Shows Promise in Elderly Leukemia Patients

A study presented at the 39th Annual American Society of Hematology (ASH) Meeting in San Diego offers the promise of an improved drug treatment, PSC833, for acute myeloid leukemia (AML).

Successful treatment of AML is limited by resistance to chemotherapy. The overexpression of the P-glycoprotein (P-gp) pump, high levels of which are associated with multidrug resistance (MDR), has been shown to be a key mechanism of drug resistance in AML. Up to 80% of newly diagnosed elderly AML patients overexpress P-glycoprotein, and prognosis is poor in this population. PSC833, developed as an MDR modulator, is specifically designed to block P-glycoprotein.

European Trial

The study of 39 patients was designed to define the safe dose of daunorubicin (Cerubidine) in combination with PSC833 and cytarabine (Ara-C) in the treatment of previously untreated AML patients 60 years of age or older. Professors B. Lowenberg, Rotterdam, The Netherlands, and A. Burnett, Cardiff, United Kingdom, were the principal investigators of this trial, which was conducted in various institutions in the Netherlands, Belgium, the United Kingdom, and Switzerland.

Many potentially effective treatments cannot be used in elderly patients because of toxicity, but patients experienced few problems with PSC833. “The study proves the safety of PSC833 in combination with chemotherapy in elderly patients with AML,” said Dr. P. Sonneveld, Rotterdam, the Netherlands, who presented the study at the San Diego meeting.

Efficacy in Patients With High P-Glycoprotein Levels

“This treatment may overcome one of the major negative prognostic factors in AML,” Dr. Sonneveld added. Unlike standard treatment, which is less effective in patients with high levels of P-glycoprotein, a regimen combining PSC833 with chemotherapy at a reduced dose was equally effective in patients with and without high levels of P-gp.”

“The results of this study are promising and justify further development of PSC833 in AML. An international randomized controlled phase III study has recently started in Europe as well as in the US, and we look forward to the results of this trial,” Dr. Sonneveld concluded.