Mechanism of Action
How DOXIL® Works
- 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
- The pegylated liposomal formulation of DOXIL® has different pharmacokinetics than conventional doxorubicin HCl3
Defining DOXIL® Mechanism of Action
- The pegylated liposomal coating allows DOXIL® to evade detection and destruction by the immune system and, as a result, increase the blood circulation time*
- Half-life of approximately 55 hours
- Remains stable in blood
- ≥90% of the drug stays encapsulated within the liposome during circulation
- DOXIL® has a small steady state and, therefore, is confined mostly to the vascular fluid
- The clinical significance of the clinical pharmacology data has not been determined.
*The exact mechanism for the release of the encapsulated doxorubicin HCl is not well understood.
†A pharmacokinetic study analyzed DOXIL® vs free doxorubicin at 2 doses in cancer patients
(N=16). Group 1 (n=7) received free doxorubicin followed by DOXIL® at the same dose (25 mg/m2
[n=3] or 50 mg/m2 [n=4]). Group 2 (n=9) received only DOXIL® in both treatments. Patients were
given either 25 mg/m2 or 50 mg/m2 up front, followed by a second course of 50 mg/m2. At
baseline, patients (male/female, 6/10) had a median performance status of 2 (range, 1-3) and a
median age of 59.5 years (range, 38-73). The study included patients with different tumor types,
including patients with ovarian cancer and patients with breast cancer. There were no patients with
multiple myeloma in this study population.