Reduced toxicity of daunorubicin by conjugation to dextran.

Daunorubicin-dextran conjugate (dau-dex) was compared to free daunorubicin for acute and subacute toxicity and efficacy in tumor chemotherapy. LD50 and LD2 values of dau-dex are about threefold higher than those of the free drug. The therapeutic index of dau-dex is also higher, manifesting a "safe-region" in which no mortality occurs either from YAC lymphoma or from drug toxicity. Dau-dex caused almost no damage to heart tissue during the 2 months following four injections of the therapeutic dose and caused no change in the differential count of bone marrow cells. Altogether, the subacute toxicity of dau-dex is much lower than that of free daunorubicin, as expressed by negligible histologic damage to all organs examined and compared to the massive atrophy of spleen and bone marrow effected by the free drug.