POLYETHYLENE GLYCOL-LIPOSOMAL DOXORUBICIN - A REVIEW OF ITS PHARMACODYNAMIC AND PHARMACOKINETIC PROPERTIES, AND THERAPEUTIC EFFICACY IN THEMANAGEMENT OF AIDS-RELATED KAPOSIS-SARCOMA

Doxorubicin is an antineoplastic drug which has in vitro and in vivo a ctivity against a number of malignancies including Kaposi's sarcoma. I ncorporation of doxorubicin into polyethylene glycol-coated (pegylated ) liposomes alters the pharmacokinetics of the drug. Liposomal doxorub icin has a smaller volume of distribution and slower plasma clearance than standard free doxorubicin. The liposomal formulation achieves hig her concentrations in the highly vascularised lesions of Kaposi's sarc oma than in normal tissue. Liposomal doxorubicin monotherapy inpatient s with AIDS-related Kaposi's sarcoma produced overall response rates ( complete plus partial) of 43 and 59% in large comparative studies and 67 to 100% in noncomparative studies which included greater than or eq ual to 20 patients. In comparative studies, liposomal doxorubicin was significantly more effective than the combination of standard doxorubi cin, bleomycin and vincristine (overall response rates of 43 and 25%, respectively) and bleomycin and vincristine (BV) [overall response rat es of 59 and 23%, respectively]. In addition, overall response rates t o the liposomal drug were higher in both treatment arms of 2 smaller c omparative studies which compared liposomal doxorubicin with BV, but s ignificant between-treatment differences were not detected. Patient nu mbers in these 2 studies, however may have been too small to detect si gnificant differences. Liposomal doxorubicin is generally well tolerat ed. Myelosuppression is the most common dose-limiting adverse effect i n patients with AIDS and Kaposi's sarcoma. Neutropenia occurs most oft en; anaemia and thrombocytopenia occur less frequently, as do nausea a nd vomiting and stomatitis. Palmar-plantar erythrodysaesthesia occurs in some patients, most commonly after 6 to 8 weeks of chemotherapy. Al though symptoms may occasionally be severe, the syndrome usually does not require dosage reduction or treatment delay. Limited data suggest that the incidence of cardiotoxicity may be lower after liposomal doxo rubicin than after equivalent doses of standard doxorubicin. Overall, liposomal doxorubicin appears to be one of the most active single agen ts available for treating patients with AIDS-related Kaposi's sarcoma. The therapeutic potential of liposomal doxorubicin administered in co mbination with other active agents to patients with Kaposi's sarcoma i s, as yet, unknown. However administered alone, the drug seems to be m ore effective than the best available combination chemotherapy regimen s.