CLINICAL EFFICACY AND TOXICITY OF DOXORUBICIN ENCAPSULATED IN GLUTARALDEHYDE-TREATED ERYTHROCYTES ADMINISTERED TO DOGS WITH LYMPHOSARCOMA

Doxorubicin was encapsulated in canine erythrocytes, treated with 0.32 % glutaraldehyde, and administered at a dosage equivalent to 30 mg of free doxorubicin/m(2) of body surface area to dogs with diagnosis of l ymphosarcoma. Compared with administration of free doxorubicin, this m ethod of drug delivery substantially reduced peak plasma concentration and prolonged higher plasma concentration of doxorubicin. As such, th is method was comparable to continuous rv infusion. Previous studies h ave indicated this method's potential for reduction in toxic side effe cts, particularly cardiotoxicosis, while allowing higher total doses o f: doxorubicin to be administered. In this study, doxorubicin encapsul ated in glutaraldehyde-treated erythrocytes induced a triphasic expone ntial decay of doxorubicin from plasma, the highest relative contribut ion to the total area of the curve being the terminal phase. The treat ment was effective in inducing complete and partial remissions of lymp hosarcoma, with minimal acute toxicosis and no evidence of cardiotoxic osis. However, substantial, unanticipated, chronic, nonregenerative my elosuppression developed, and was most strikingly expressed as profoun d thrombocytopenia. Efforts to ameliorate or circumvent this toxic eff ect will be required prior to further consideration of this doxorubici n delivery system for treatment of systemic neoplasia.