| Title | Pharmacokinetics of doxorubicin administered i.v. as Myocet (TLC D-99; liposome-encapsulated doxorubicin citrate) compared with conventional doxorubicin when given in combination with cyclophosphamide in patients with metastatic breast cancer. | | Author(s) | Swenson CE, Bolcsak LE, Batist G, Guthrie TH, Tkaczuk KH, Boxenbaum H, Welles L, Chow SC, Bhamra R, Chaikin P | | Institution | Elan Pharmaceuticals, Inc, Princeton, NJ 08540, USA. christine.swenson@elan.com | | Source | Anticancer Drugs 2003 Mar; 14(3):239-46. | | MeSH | Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Area Under Curve
Breast Neoplasms
Chromatography, High Pressure Liquid
Clinical Trials, Phase III
Comparative Study
Cyclophosphamide
Doxorubicin
Female
Half-Life
Humans
Infusions, Intravenous
Leukocyte Count
Liposomes
Metabolic Clearance Rate
Middle Aged
Neoplasm Metastasis
| | Abstract | Myocet (TLC D-99) is a liposomal formulation of the anti-neoplastic drug doxorubicin with an improved therapeutic index compared with conventional doxorubicin. The objective of this study was to assess the plasma disposition of doxorubicin when administered i.v. as TLC D-99 and to compare this to conventional drug. Metabolite (doxorubicinol) plasma levels were also quantitated in both treatment groups. Plasma was collected during the first course of treatment from 10 patients receiving TLC D-99 60 mg/m and 10 receiving conventional doxorubicin 60 mg/m2, each with cyclophosphamide 600 mg/m2. Samples were assayed for total doxorubicin (all doxorubicin regardless of whether it is encapsulated or not), encapsulated doxorubicin (TLC D-99 group only) and doxorubicinol using high-performance liquid chromatography. Plasma concentrations of total doxorubicin were higher in patients receiving TLC D-99 than in patients receiving conventional doxorubicin. The clearance of total doxorubicin after administration of TLC D-99 was lower (approximately 9-fold) and the volume of distribution at steady state was less (25-fold) than that of doxorubicin after conventional drug. Doxorubicinol was detected in the plasma of all patients in both treatment groups. The mean AUC(0-infinity) of doxorubicinol for patients receiving TLC D-99 (1.5+/-0.4 M x h) was not statistically different than that in patients receiving conventional doxorubicin (1.8+/-0.4 M x h), although the appearance of the peak doxorubicinol concentration occurred later and was lower in patients receiving TLC D-99. There was a correlation between the plasma AUC(0-infinity) of total doxorubicin and the degree of myelosuppression in patients receiving conventional doxorubicin, but this correlation was not found in patients receiving TLC D-99. | | Language | eng | | Pub Type(s) | Clinical Trial
Journal Article
Multicenter Study
Randomized Controlled Trial
| | PubMed ID | 12634619 |
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