Doxil®

What is Doxil?

Doxil, also known as doxorubicin HCl liposome injection or pegylated liposomal doxorubicin (PLD), is a chemotherapy drug used in cancer treatment. It is a reformulated version of doxorubicin (Adriamycin), a cancer drug that has been used for many years in traditional chemotherapy regimens in multiple myeloma. It is distributed by Janssen Products, LP in the United States.


How is Doxil used in multiple myeloma?

Doxil is typically used with other anticancer agents to treat cancer. Doxil is often used in place of conventional doxorubicin, and it is also used as part of novel combination therapies.

Doxil is approved by the FDA for use in combination with Velcade (bortezomib, Takeda Oncology) to treat patients with myeloma who have not previously received Velcade and have received at least one prior therapy. Results of clinical trials show that adding Doxil to a standard Velcade regimen reduced the risk of the disease progressing and prolonged the duration of response in patients with relapsed and refractory disease better than Velcade alone.

How does Doxil work?

Doxil is a reformulated version of the drug doxorubicin (Adriamycin). Doxorubicin is a chemotherapy agent that belongs to a class of agents referred to as anthracyclines which damage the DNA in cancer cells and cause them to die.

With Doxil, the doxorubicin is wrapped in a “fat bubble” (liposome), which serves to help slowly release the drug and may help reduce side effects. The liposomes are also coated with polyelethylene glycol in a process called pegylation, which helps the liposomes stay in the circulation longer.

What types of patients can benefit from Doxil therapy?

Results of the clinical trial that led to Doxil’s approval showed that the combination of Doxil and Velcade is effective in a wide range of patients with relapsed/refractory myeloma, including:

  • Older patients (≥65 years old) as well as younger patients
  • Patients who have previously received a stem cell transplant
  • Patients who have previously received Thalomid® (thalidomide, Celgene) or Revlimid® (lenalidomide, Celgene)
  • Patients who have previously received doxorubicin
  • Patients with “high-risk” disease (poor prognosis)
    • Velcade-Doxil was beneficial to patients with chromosome abnormalities and those with elevated levels of beta 2-microglobulin

How is Doxil administered?

Doxil is administered as an injection directly into the vein (intravenously, or IV). When Doxil is used along with Velcade in the treatment of myeloma, the recommended dosing over each 28-day cycle is as follows:

  • Velcade is given at a dose of 1.3 mg/m2 intravenously or as an injection under the skin on days 1, 4, 8, and 11.
  • Doxil is given intravenously at a dose of 30 mg/m2 over a 1-hour infusion on day 4 after Velcade is given.

In general, patients are treated for up to 8 cycles until their disease progresses or they experience unacceptable toxicity.

Although there is limited information available on use of Doxil in patients with myeloma with reduced liver (hepatic) function, it is recommended that patients with hepatic impairment receive a lower dose of Doxil.


What are Doxil side effects?

Like many other chemotherapy drugs, Doxil can have a number of different side effects. Side effects vary depending on an individual’s past health history and current multiple myeloma stage. Doxil is associated with less frequent side effects than conventional Adriamycin. The most common side effects observed in the clinical trial that led to the approval of combination therapy with Velcade and Doxil were:

  • Gastrointestinal effects (ie, nausea, vomiting, diarrhea, and constipation)
  • Numbness or pain in hands or feet (peripheral neuropathy)
  • Fatigue or weakness
  • Low red blood cells, white blood cells, or platelets (anemia, neutropenia, thrombocytopenia)
  • Fever
  • Mouth sores (stomatitis)
  • Rash

Serious side effects seen with Doxil-Velcade combination therapy

In the trial that led to Doxil’s approval, a number of patients with relapsed myeloma receiving Velcade-Doxil combination therapy experienced serious (Grade 3) or less commonly, very serious (Grade 4) side effects during the course of their treatment. These serious side effects included:

  • Low red blood cells, white blood cells, or platelets (anemia, neutropenia, thrombocytopenia)
  • Fatigue or weakness
  • Diarrhea
  • Numbness or pain in hands and feet (peripheral neuropathy)
  • Hand-foot syndrome (HFS), a severe skin reaction resulting in redness, tenderness, and possibly peeling of the skin on the palms of the hand and soles of the feet

Other possible serious side effects of Doxil therapy

Although rare, severe infusion-related reactions, such as difficulty breathing or low blood pressure, may occur, most often during the first cycle of treatment. If such a reaction occurs, the infusion of Doxil will be temporarily stopped until symptoms have resolved and the infusion will be restarted at a slower rate. Doxil will be discontinued if the reaction is severe.

A potential side effect of long-term Doxil therapy is damage to the heart muscle (myocardial damage). Myocardial damage is related to the total dosage of doxorubicin a patient has received over time, which includes both conventional doxorubicin and Doxil. For this reason, it is generally recommended that patients receive a total of no more than 550 mg/m2 of doxorubicin over time. A lower total cumulative dose may be recommended if a patient has received radiotherapy to the area of the heart, or therapy with other agents that are potentially toxic to the heart, such as cyclophosphamide.

Doxil is potentially less toxic to heart muscles than conventional doxorubicin. This is mainly because there are much lower circulating levels of free doxorubicin in the blood when Doxil is used.

Doxil can cause harm to a fetus, so it should not be used during pregnancy. Women must use effective contraception during and for 6 months after treatment with Doxil.

How are side effects of Velcade-Doxil managed?

Patients experiencing side effects with Velcade-Doxil may have their dose reduced or delayed until symptoms resolve.


What have Doxil clinical trials shown?

 

Doxil clinical studies resulted in an FDA approval for multiple myeloma treatment.

Doxil was approved for use in combination with Velcade to treat patients with myeloma who have not previously received Velcade and have received at least one prior therapy. The approval was based on results of a planned interim analysis of an international Phase 3 trial (DOXIL-MMY-3001) that compared the combination to Velcade alone in 646 patients with relapsed/refractory myeloma.

The results of this study showed that adding Doxil to the standard Velcade regimen reduced the risk of the disease progressing and prolonged the duration of response in patients with relapsed and refractory disease compared with Velcade alone.

  • The combination significantly extended the median time to disease progression (TTP) compared with Velcade alone from 6.5 months to 9.3 months, reflecting a 63% reduction in the risk of disease progression or death.
  • On average, responses to the combination lasted 10.2 months compared with 7 months with Velcade alone.
  • The benefits of the combination were consistently seen across a variety of patient types, including older patients, those with prior stem cell transplantation or exposure to Thalomid or doxorubicin, and patients with markers of high-risk disease.
  • After a follow-up of 8.6 years, overall survival was similar for patients in the Velcade-Doxil group and the Velcade group.

What have other clinical studies shown?

A variety of combination therapies that include Doxil have been shown to be effective in patients who have previously received other therapies. Doxil has been combined with agents such as Velcade, Revlimid, Thalomid, and/or dexamethasone in a number of 3- and 4-drug regimens.

Interested in learning more about Doxil clinical trials? Talk to an MMRF Patient Navigator to learn more or use our clinical trials finder:

FIND CLINICAL TRIALS

Updated February 2018

Please visit the sponsor’s official patient site for up-to-date information on Doxil.