Liposomal characteristics, serum and tissue pharmacokinetics of Caelyx (R)in patients with advanced breast cancer

Caelyx(R) is a formulation of doxorubicin encapsulated in pegylierte liposo mes. As a result of the high liposome stability, the elimination rate from plasma is significantly decreased compared with that of free doxorubicin. F ollowing a single dose of Caelyx 50 mg/m(2) given as a 30-min infusion to p atients with advanced breast cancer, the area under the curve (AUC) for pla sma doxorubicin at 24 h was 67 times higher than after infusion of non-enca psulated doxorubicin at the same dose. The distribution volume of Caelyx wa s similar to the human blood volume, the plasma clearance was approximately 150 ml/h/m(2). In long-term studies we detected measurable doxorubicin pla sma levels even at 3 weeks following administration of Caelyx. It appears t hat the liposomes can extravasate relatively freely through the fenestrated endothelium of the tumor vasculature. In keeping with this concept, the ti ssue concentrations of doxorubicin th at we found in the tumors of patients treated with Caelyx were twice that of surrounding healthy tissues. The st ability of pegylated liposomes is not affected by the combined administrati on of the taxane docetaxel. Hypersensitivity reactions due to Caelyx(R) can be largely avoided by prolonging the infusion duration from 30 to 60 min. If Caelyx is given at intervals of 4 to 5 weeks, cutaneous toxicity (foot-h and syndrome) will also remain manageable.