The use of mitoxantrone and melphalan prior to stem cell transplantation in multiple myeloma patients results in favorable survival rates and manageable side effects, according to the results of a Phase 2 clinical trial.

Although the results of the study are encouraging and confirm the results of previous trials, Dr. Anne Beaven, from Duke University Medical Center and lead author of the study, noted that the trial was conducted before the introduction of novel agents into routine clinical practice.

“Until a trial is performed combining this regimen with maintenance Revlimid ^[1] (lenalidomide) or a Velcade ^[2] (bortezomib) regimen or some of our newer agents, it is difficult to truly know if our approach of infusional mitoxantrone (Novantrone) really offers significant benefit to our patients,” she cautioned.

Mitoxantrone is an anthracenedione, which disrupts the generation and repair of DNA in cancer cells.  The drug is currently used to treat a number of blood and solid tumor cancers and can also be used to treat multiple sclerosis.

Anthracenediones are very similar to a class of drugs called anthracyclines. Anthracyclines, such as Doxil ^[3] (doxorubicin liposomal), are a class of useful chemotherapeutic drugs for the treatment of multiple myeloma and other cancers.

The researchers hypothesized that the addition of mitoxantrone to a melphalan ^[4] (Alkeran)-based regimen prior to stem cell transplantation would improve outcomes in multiple myeloma patients.

In this Phase 2 study, researchers evaluated the efficacy and safety of high-dose melphalan combined with a prolonged infusion of mitoxantrone as a preparative regimen for autologous stem cell transplantation.

According to Dr. Beaven, the most novel part of the study was the way in which the drug was administered. Rather than administering mitoxantrone as a quick, single injection, it was infused slowly over two days.

“This is interesting because it is becoming increasingly clear that when treating cancer it not only matters what drugs we use but how they are given (slowly or quickly) and sometimes even in which order they are given.  Simply changing around how a drug is used may increase its efficacy,” she stated in email correspondence with the Beacon.

A total of 35 patients with multiple myeloma were enrolled in the trial between 1998 and 2002. Of the enrolled patients, 57 percent had received more than 2 prior chemotherapies.

More than seven years after transplantation, 37 percent of patients were still alive.  Four patients survived more than nine years post-transplant, and two survived more than a decade post-transplant. The median overall survival was 5 years and 8 months, and the median progression-free survival was 22 months.

Patients were hospitalized for a median of 20 days during the transplantation procedure. The median time to platelet and white blood cell recovery was 9 and 11 days, respectively, which the researchers noted is similar to what is seen in other transplant trials.

The mitoxantrone-melphalan regimen was well tolerated in most patients. Short-term fever associated with low blood cell counts was experienced by 83 percent of patients. Inflammation and ulceration of the digestive tract lining was also a common side effect of treatment.

Although the results of this study may not immediately offer significant benefits to myeloma patients, Dr. Beaven offered the encouraging remark, “This is a good time for patients with multiple myeloma because there is extensive ongoing research into novel treatment options, maintenance therapy, and different drug combinations, which are improving outcomes.”

For more information, see the study in the journal Cancer Investigation ^[5] (abstract).