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, or the prescribing information.

Diseases for which it is established (work in progress)

• Ovarian cancer
  • Low-grade serous ovarian cancer

Diseases for which it is used

• Breast cancer
• Endometrial cancer
• Esophageal cancer
• Hemophagocytic lymphohistiocytosis
• Lymphoma
  • Diffuse large B-cell lymphoma
  • HIV-associated lymphoma
  • Classical Hodgkin lymphoma
• Kaposi sarcoma
• Multiple myeloma
• Plasma cell leukemia
• Soft tissue sarcoma
  • Desmoid tumors

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

AIDS-related Kaposi’s sarcoma

• 1995-11-17: Initial 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. (Based on Harrison et al. 1995)
  • 2008-06-10: Converted to regular approval.
• 2013-02-04: Approved for AIDS-related Kaposi’s sarcoma after failure of prior systemic chemotherapy or intolerance to such therapy. (Requirement for prior combination chemotherapy removed)

Multiple myeloma

• 2007-05-17: 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. (Based on MMY-3001)

Ovarian cancer

• 1999-06-28: Accelerated approval 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. (Based on Muggia et al. 1997 & Gordon et al. 2000)
  • 2005-01-28: Converted to regular approval for metastatic ovarian carcinoma refractory to paclitaxel and platinum-based chemotherapy. (Based on Doxil Study 30-49)
• 2013-02-04: Approved for the treatment of ovarian cancer in patients whose disease has progressed or recurred after platinum-based chemotherapy. (Approval extended to platinum-sensitive disease)

History of changes in EMA indication

• 1996-06-20: Initial marketing authorization as Caelyx.

History of changes in Health Canada indication

• 1998-07-20: Initial notice of compliance

History of changes in PMDA indication

• 2009-04-22: New indication and a new dosage for the treatment of ovarian cancer which has progressed after cancer chemotherapy.

Also known as

• Generic names: doxorubicin HCl liposome injection, PLD
• Brand names: Caelyx, Celdoxome, Doxil, Doxosome, Doxulip, i-dox, Lipodox, Lippod, Natdox, Pegadria, Pegdoxine, Peglidox, Peg-Doxorub, Zolsketil