Understanding how DOXIL® works1-7
- Anthracyclines, used alone or in combination with other agents, have long been an integral part of some of the most active therapies for hematologic and solid tumors1,2
- DOXIL® (doxorubicin HCl liposome injection), an anthracycline topoisomerase II inhibitor, is encapsulated in STEALTH® liposomes for intravenous use3
- Greater than 90% of the drug is encapsulated in the STEALTH® liposomes3
- The mechanism of action of doxorubicin HCl, the active ingredient, is thought to be related to its ability to bind DNA and inhibit nucleic acid synthesis. Cell structure studies have demonstrated rapid cell penetration and perinuclear chromatin binding, rapid inhibition of mitotic activity and nucleic acid synthesis, and induction of mutagenesis and chromosomal aberrations3
STEALTH® liposomes deliver doxorubicin HCl3-7
- STEALTH® technology is a liposomal coating that evades detection and destruction by the immune system4,5
- The pegylated liposomes are small and can pass into tumors*6
- At least 90% of doxorubicin measured in the plasma remained encapsulated in the liposome during circulation3
- DOXIL® concentration is higher in malignant tissue than in healthy tissue*7
- Encapsulation in STEALTH® liposomes enables DOXIL® to penetrate the leaky membranes that are commonly found in cancer tissue. DOXIL® may also affect normal tissue4,5
Prolonged plasma levels following infusion†3
- Second phase half-life of a DOXIL® 20 mg/m2 dose was approximately 55 hours†3
- Plasma clearance of total doxorubicin following DOXIL® administration at a dose of 20 mg/m2 was 0.041 L/h/m2 vs 24 L/h/m2 to 35 L/h/m2 with conventional doxorubicin3
- The pharmacokinetic parameters for total doxorubicin reported were following a single dose of DOXIL® infused over 30 minutes in a refractory or intolerant AIDS-related Kaposi's Sarcoma patient population3
*Correlation to clinical effect has not been established.
†DOXIL® displayed linear pharmacokinetics over the range of 10 mg/m2 to 20 mg/m2. Relative to DOXIL® doses at or below 20 mg/m2, the pharmacokinetics of total doxorubicin following a 50 mg/m2 DOXIL® dose are nonlinear. At this dose, the elimination half-life of DOXIL® is longer and the clearance lower compared to a 20 mg/m2 dose.3
DOXIL® and STEALTH® are registered trademarks of ALZA Corporation.
Rubin EH, Hait WN. Anthracyclines and DNA Intercalators/epipodophyllotoxins/campthothecins/DNA topoisomerases. In: Kuf DW, Pollock RE, Weichselbaum RR, et al, eds. Holland-Frei Cancer Medicine. 6th ed. Hamilton, ON: BC Decker; 2003. www.ncbi.nih.gov/books/NBK12354/. Accessed September 13, 2016.
Hortobagyi GN. Anthracyclines in the treatment of cancer. Drugs. 1997;54(suppl 4):1-7.
DOXIL® (doxorubicin HCl liposome injection) Prescribing Information. Janssen Products, LP, Horsham, PA.
Working PK, Newman MS, Huang SK, et al. Pharmacokinetics, biodistribution and therapeutic efficacy of doxorubicin encapsulated in STEALTH® liposomes (DOXIL®). J Liposome Res. 1994;4:667-687.
Bulbake U, Doppalapudi S, Kommineni N, et al. Liposomal formulations in clinical use: an updated review. Pharmaceutics. 2017;9(2)12. doi:10.3390/ pharmaceutics9020012.
Gabizon A, Shmeeda H, Barenholz Y. Pharmacokinetics of pegylated liposomal doxorubicin: review of animal and human studies. Clin Pharmacokinet. 2003;42(5):419-436.
Northfelt DW. Liposomal anthracycline chemotherapy in the treatment of AIDS-related Kaposi's Sarcoma. Oncology. 1997;11(10)(suppl 11):21-32.