Doxorubicin pharmacokinetics following two different liposomal formulations (CAELYX™ vs MYOCET™) in advanced breast cancer patients

• Published in: Cancer research (Chicago, Ill.) Vol. 69; no. 2_Supplement; p. 2128
• Main Authors: Schueller, J, Czejka, M, Krexner, E, Aigner, K, Gruenberger, B
• Format: Journal Article
• Language: English
• Published: 15-01-2009
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.SABCS-2128

Abstract #2128
Background: Liposomal encapsulation of Doxorubicin (DOX) was designed to minimize healthy tissue distribution by altering pharmacokinetics (PK) thus reducing cardiotoxicity while preserving antitumour efficacy. Study objective was to compare the PK behaviour of the two main liposomal formulations of DOX, i.e. pegylated (Caelyx, C) versus non pegylated (Myocet, M), in a single center study including 17 MBC patients, all Anthracyclin pretreated with additional risk faktors.
 Methods: Cohort 1 consisted of 10pts (mean age 62, 49-77) treated by C as 1HR infusion of 50mg/m²/4 wks. Plasma samples were collected at timepoints min 0, 30, 60, 120, 180 and d1, 7, 14, 28. In cohort 2, 7 pts (mean age 58, 51 – 70) received M 75mg/m² 1H Infusion / 3wks, plasma levels determined at min 0, 30, 60, 90, 120, 180 and d1, 2, 3. Total amount of DOX was determined following the 1st infusion respectively, analytic procedure included solid phase extraction quantification by HPLC and PK analysis by Win Nonlin Pro. Doxorubicinol was detected after M only.
 Results: in Cohort1 after C, mean Cmax of 6.8 µg/ml surprisingly occured at a mean tmax of 2.3 d, log conc time curve showed linear decrease of DOX conc suggesting continuous release into the tissue (mean conc d 7 3.3, d 14 1.0, d 21 0.3, d 28 0.09 µg/ml) . No metabolites were found, AUC (does not represent reliable drug exposure and bioavailability of DOX) expressed as µg/ml.d was 54.6. In contrast AUClast of M was calculated as 35µg ml.H and mean Cmax by 7.5 µg/ml at infusion end. DOXol was measured in all M treated patients at a slower metabolisation rate and late appearance compared to conventional DOX. t/2 el of C was 6 times longer than that of M (HR 90 vs 15). Differences in plasma disposition and PK of M vs C are depicted in table 1 and compared to pooled data of conventional DOX derived from former studies (50 mg/m² 30min inf, n=40). Cltot of conv. DOX was 10 fold higher than M and 500 fold higher than C, Vss about 12 times that of M and 70 times that of C. These PK differences underlines a different toxicity profile between PEGL (C, PPE syndrome) and NPEGL (M, myelotox, nausea), both reducing cardiac tox by avoiding peak plasma levels due to prolonged circulation time.
 

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2128.