Mitoxantrone: Update on Cardiac Risk

This article was written by the neuro I saw in Boston a couple of years ago to get a second opinion on mitoxantrone.  At the time my newly dx'ed RRMS was very active/aggressive (serious relapses every few months) and my regular neuro suggested I might need to consider this more aggressive treatment.  I was worried about all I had read about this drug; sought Dr. Stankiewicz's opinion, and he said flat out "We [Partners MS Center in Boston] hate that drug."  I stayed put on Copaxone and so far this seems to have been the right decision for me as my MS has been pretty stable the past couple of years.  

Anyway, read on for an update on this drug:

Mitoxantrone: Update on Cardiac Risk

In a retrospective chart review, posttreatment cardiotoxicity occurred more frequently than was observed in clinical trials.

In 2000, mitoxantrone was approved by the FDA for secondary progressive, worseni...ng relapsing-remitting, and progressive-relapsing forms of multiple sclerosis (MS). The drug's use has been limited by concerns about potential cardiotoxicity and acute leukemia. To provide more data on its cardiotoxicity, researchers conducted this retrospective chart review of 163 patients followed at their clinic for nearly 10 years.

Median follow-up duration was slightly more than 1 year, and mean cumulative dose (59.7 mg/m2) was well below the suggested lifetime ceiling of 140 mg/m2. Nonetheless, 14% of mitoxantrone-treated patients with normal baseline left ventricular ejection fractions experienced decreased ejection fractions on follow-up multiple-gated acquisition (MUGA) scans. This effect persisted in half of these patients and reversed in three patients (17%); the other six patients did not receive a follow-up MUGA study. One patient developed congestive heart failure. Sex, age, disease duration, and cumulative dose were not predictors of cardiac risk. The authors also identified other adverse effects of mitoxantrone (neutropenia, liver toxicity, and anemia).

Comment: Recently, the FDA imposed stringent guidelines for mitoxantrone use, requiring that treated patients undergo annual echocardiograms indefinitely to detect late-developing cardiac damage. Although this study showed no relation between total dose and cardiac effect, other studies involving higher mean dosages have done so. The lack of association in this study likely reflects the restricted dosing range. The cardiotoxicity reported here is greater than was seen in the phase II and III trials and in some but not all postmarketing studies. This difference is especially noteworthy considering the low cumulative doses and short follow-up. Taken together with other postmarketing work, including some studies suggesting a risk for leukemia as high as 3% with mitoxantrone (Neurology 2010; 74:1463), these finding clearly indicate that clinicians must carefully consider safety risks before prescribing mitoxantrone.

— James Stankiewicz, MD

Dr. Stankiewicz is Director of Clinical Education, Partners MS Center, and Instructor in Neurology, Harvard Medical School, Boston.

Published in Journal Watch Neurology September 28, 2010

Citation(s):

Kingwell E et al. Cardiotoxicity and other adverse events associated with mitoxantrone treatment for MS. Neurology 2010 Jun 1; 74:1822.

[rendean]

Thanks for the update!
Ren

[Quixotic1]

Whooa!  I knew the cardiotoxicity was a real concern, but I find this dismaying.  Add to that a possible greater that 1 in 3 chance of later developing leukemia, and I question whether the cure is worse than the disease.  Of course, I'm not suffering rapidly aggressive  MS disease.

I think I hate this drug, too.

Quix