Immobilized forms of daunorubicin in patients with acute leukemia

Aim. To study pharmacokinetics of liposomal daunorubicine DaunoXome and dau norubicine (rubomycin) associated with red cells; to assess their effective ness and toxicity in patients with acute leukemia. Materials and methods. 7 patients with resistant or recurrent acute leukemi a entered the trial. Of them 2 patients had acute myeloid leukemia. They re ceived DaunoXome in dose 100 mg in days 1, 2 and 3 of 7+3 program. 1 patien t had pretreated acute promyelocytic leukemia. This patient received 5-day course of DaunoXome in a dose 100 mg in the presence of ATRA therapy. 4 pat ients were given single dose daunorubicin associated with autoerythrocytes in the courses RACOP and 7+3 in a dose 45 mg/m(2). Concentrations of free, bound and liposomal daunorubicin were determined spectrofluorimetrically in chlorophorm extracts of plasm, blood, liquor and bone marrow specimens. Results. Immobilization of daunorubicin on the red cells and liposomes chan ges pharmacokinetics of the drug: peak concentrations change and the area u nder the concentration curve increases. Tolerance of DaunoXome and daunorub icine associated with red cells was satisfactory in all the cases: clinical and echo-CG signs of cardiotoxicity were absent, myelotoxicity was similar to that of free daunorubicine. DaunoXome was effective in 2 of 3 patients with acute myeloblastic leukemia. Conclusion. The findings are of practical interest for physicians designing new programs of therapy of acute leukemia.