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Addition Of Doxil To Velcade Improves Treatment Outcomes For Multiple Myeloma Patients

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Published: Oct 5, 2011 12:21 pm

European researchers found that the addition of Doxil to Velcade significantly extends the time to disease progression in relapsed / refractory multiple myeloma patients, regardless of age, number of previous therapies, disease stage, and resistance to previous therapy.

However, the addition of Doxil increased the rate of side effects in all patients. Despite the increased rate of side effects, the researchers suggested that Velcade plus Doxil should be considered as an additional standard of care option for myeloma patients, especially those with high-risk disease.

In the last decade, the introduction of novel agents, such as Velcade (bortezomib), Revlimid (lenalidomide), and thalidomide (Thalomid), has dramatically changed the standard of care for multiple myeloma. Research has shown that these new drugs significantly improve treatment outcomes, especially when used in combination therapies.

Doxil (doxorubicin liposomal), which is a new formulation of the anticancer drug doxorubicin (Adriamycin), is approved in the United States for use with Velcade to treat myeloma patients who have received at least one prior therapy other than Velcade.

Recent clinical studies have suggested that the combination of Velcade and Doxil is superior to Velcade alone in relapsed and/or refractory (resistant) myeloma patients.

Based on these results, European researchers aimed to identify which patients would benefit most from the Velcade-Doxil combination. Therefore, they retrospectively analyzed data from a Phase 3 clinical trial that included 646 relapsed and/or refractory myeloma patients. In the trial, participants were randomly assigned to receive treatment with Velcade and Doxil or Velcade alone.

In the retrospective analysis, the researchers analyzed how certain low-risk and high-risk patient groups responded to Velcade plus Doxil therapy compared to Velcade alone.  Specifically, they analyzed responses based on patient characteristics, such as age (less than 65 years of age versus 65 years or older), number of previous lines of therapy (one versus two or more), disease stage (early stage versus later stage), and response to previous line of therapy (non-refractory or refractory).

For all patient groups analyzed, response rates were similar or better with Velcade plus Doxil as compared to Velcade alone.  Response rates were significantly better for patients younger than 65 years of age, those who had received at least two prior therapies, and those who were not refractory to their previous therapy.

Overall, patients treated with Velcade plus Doxil had a significantly longer time to disease progression compared to those who received Velcade alone (9.3 versus 6.5 months).  This held true for all patient groups analyzed, except those with early stage disease, in which there was a trend toward longer time to disease progression, but the difference was not statistically significant.

The median duration of response was also longer, overall, for patients treated with Velcade plus Doxil (10.2 months versus 7.0 months) as well as for all patient groups analyzed.

The addition of Doxil, however, increased the rate of side effects from 64 percent to 80 percent and the rate of serious side effects from 15 percent to 22 percent.

Patient characteristics did not affect the frequency of side effects.  The frequency in patients with high-risk characteristics was comparable to the frequency in the overall patient population.

In addition, the researchers found that the addition of Doxil did not increase the frequency of peripheral neuropathy, a known side effect of Velcade that results in pain and tingling in the arms, hands, legs, and feet.

For more information, please see the study in the journal Clinical Lymphoma, Myeloma & Leukemia (abstract).

Photo by IndyDina with Mr. Wonderful on Flickr - some rights reserved.
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7 Comments »

  • Suzanne Gay said:

    After 6 months of Doxil/Velcade, I asked to switch off to cytoxan (option given earlier) because of the side effect Hand-Foot Syndrome, which makes them sensitive, dry, cracked, and sometimes useless. The Doxil folks said the effect would disappear after 2 weeks off treatment. It is now 6 weeks and I see no improvement. In the larger picture, the treatment dropped the M spike from 1.6 to 0.6 during this period, and we will see how far down it can go now with cytoxan. So all is well, I guess. Suzanne

  • suzierose said:

    Is Adriamycin lifetime dose limited due to cardiotoxicity?

  • Scott said:

    I believe there is a cumulative dose limit for Adriamycin. My wife received six cycles of Doxil along with Velcade and Decadron. Didn't have side effects bad enough to discontiue and she achieved a CR. I have talked to a number of Myeloma patients and Revlamid seems to be the choice of most doctors to pair with V and D now. It sounds like Doxil is less a frontline drug now.

  • Myeloma Beacon Staff said:

    SuzieRose and Scott,

    Yes, the FDA-approved prescribing information for Doxil does include a warning that the total lifetime dose of the drug's active ingredient (doxorubicin) should not exceed 550 mg/m2. This is because the drug can damage the heart, and the greater the lifetime dose of the drug, the greater the risk of heart failure.

    Lower lifetime doses (400 mg/m2) also can cause heart failure if a patient has received radiation treatment targeted at the central chest area, of if the patient has been treated with certain other drugs, including cyclophosphamide.

    The recommended dose for one infusion of Doxil when treating myeloma is 30 mg/m2. This means that a myeloma patient could be dosed up to 18 times with Doxil at the recommended dose before the lifetime dose would reach the 550 mg/m2 limit.

    The Doxil prescribing information recommends that all patients being treated with the drug should have their heart function carefully monitored during treatment.

  • suzierose said:

    Sooo

    how does a MM patient decide? Does the risk of cardiotoxicity with doxorubicin out weigh survival?

    IOW's if you risk the cardiotoxicity will you survive longer? Are there studies that show that difference?

    Just wondering.

  • christad said:

    Unfortunately, if your doctor wants you to get Doxil in combination with Velcade and you're newly diagnosed, you probably can't get it. J&Js supplier shut down production and no restart or alternative supplier in sight. Got one round, not available for current round. Waiting and hoping . . .

  • christad said:

    Oops, meant Janssen, not J&J