Pegylated liposomal doxorubicin (Doxil)

General information

Class/mechanism: Anthracycline; binds and intercalates into DNA, inhibiting nucleotide replication and DNA/RNA polymerase activity. Causes DNA cleavage through interaction with topoisomerase II.

Doxorubicin is encapsulated in long-circulating STEALTH® liposomes, which are microscopic vesicles made of a phospholipid bilayer. The liposomes are pegylated with surface-bound methoxypolyethylene glycol (MPEG) to increase circulation time and protect them from detection by the mononuclear phagocyte system (MPS). Their 100 nm size and long circulation may aid their ability to penetrate the altered vasculature of tumors. Exact mechanism of release of the active drug contained within the liposome is not understood.
Route: IV
Extravasation: irritant

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Diseases for which it is used

• Breast cancer
• Diffuse large B-cell lymphoma
• Esophageal cancer
• Hemophagocytic lymphohistiocytosis
• HIV-associated lymphoma
• Hodgkin lymphoma
• Multiple myeloma
• Plasma cell leukemia
• Ovarian cancer
• Uterine cancer
• Vascular sarcoma

Patient drug information

• Pegylated liposomal doxorubicin (Doxil) patient drug information (Chemocare)
• Brief patient counseling information can be found in the Pegylated liposomal doxorubicin (Doxil) package insert
• Pegylated liposomal doxorubicin (Doxil) patient drug information (UpToDate)

History of changes in FDA indication

• 11/17/1995: Initial FDA approval for "treatment of AIDS-related Kaposi’s sarcoma in patients with disease that has progressed on prior combination chemotherapy or in patients who are intolerant to such therapy."
• 6/28/1999: FDA approved for "treatment of metastatic carcinoma of the ovary in patients with disease that is refractory to both paclitaxel- and platinum-based chemotherapy regimens. Refractory disease is defined as disease that has progressed while on treatment, or within 6 months of completing treatment."
• 5/17/2007: FDA approved "for use in combination with bortezomib in patients with multiple myeloma who have not previously received bortezomib and have received at least one prior therapy."

Also known as

• Generic names: doxorubicin HCl liposome injection, PLD
• Brand names: Caelyx, Doxil