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DIR Return to: NOVANTRONE (mitoxantrone)
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#Post#: 1796--------------------------------------------------
Older MS drugs {Novantrone, Imuran, Cytoxan] may boost cancer ri
sk
By: agate Date: August 24, 2017, 7:56 pm
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From MedPage Today, August 14, 2017:
[quote]Older MS Drugs May Boost Cancer Risk
But MS alone doesn't raise cancer risk, Sicilian study finds
by Thomas Walsh, MedPage Today Intern
Patients with multiple sclerosis who took older immune
suppressors had an increased risk of cancer, data from a
Sicilian study showed.
In a single-center cohort, MS patients exposed to three older
immunosuppressant drugs -- azathioprine (Imuran), mitoxantrone
(Novantrone), and cyclophosphamide (Cytoxan) -- had a
significantly greater risk of cancer compared with those not
exposed (HR 11.05, 95% CI 1.67-73.3, P=0.013), Paolo Ragonese,
MD, of the University of Palermo in Italy and colleagues,
reported online in BMC Neurology.
The risk seemed to be driven by azathioprine and mitoxantrone,
as there were no cancer deaths in those treated with
cyclophosphamide in this study, the researchers said.
Even though newer drugs that are thought to have a better safety
profile are now on the market, there are still MS patients "who
do not respond to available drugs and experience an unfavorable
disease course, rapidly accumulating disability, or patients who
have lack of tolerance and need therefore a therapeutic
alternative," the researchers wrote.
"In all of these patients, a strict long-term follow-up must be
planned to avoid life-threatening conditions," they said.
Ragonese and colleagues studied 531 MS patients exposed to
immune suppressants from 1994 to 2011 for a mean of nine years,
and compared them with 531 MS patients who didn't take these
drugs. Both MS groups consisted of 346 women and 185 men between
ages 18 and 54. The researchers also compared cancer incidence
in MS patients with cancer incidence in the general population
of Sicily in similar age groups.
They found that those treated with azathioprine (median exposure
5 years) or mitoxantrone (median exposure 1 year) had a fourfold
increased risk of cancer compared with MS patients who were not
exposed. Among 346 patients treated with azathioprine, seven
developed cancer in various sites (three breast, two gut, one
brain, one ovary). Among 262 patients treated with mitoxantrone,
six developed cancer (three leukemia, one gut, one lung, one
pancreas).
"The association between the exposure to mitoxantrone and
various forms of adult onset leukemia has been seen across Italy
and elsewhere," said Jerry Wolinsky, MD, of the McGovern Medical
School at UTHealth in Houston, who was not involved in the
study. "That, plus its cardiotoxicity, has resulted in limiting
the total dose that's supposed to be given and the fact that
mitoxantrone came and went on the therapeutic horizon fairly
quickly."
There was no association between cancer and cyclophosphamide
exposure, but this accounted for the smallest group and
follow-up wasn't as long, the researchers noted.
When compar[ed] with the general Sicilian population, MS
patients on immunosuppressants had a fourfold higher rate of
cancer -- but there was no difference in cancer incidence for MS
patients who didn't take the drugs, they found. (SIR 0.97, CI
0.96-0.98). This is consistent with data found in other national
registries, Wolinsky said.
Jeffrey Cohen, MD, of the Cleveland Clinic, who wasn't involved
in the study, said it makes the "important point that the risk
of cancer does not appear to be increased by MS alone."
The study was limited because the authors couldn't account for
confounding environmental risk factors for cancer like smoking,
given the data available. Also, all subjects were from the same
geographic area, which could limit the applicability of the
results to groups outside of Sicily.
At the same time, however, the results could apply to patients
without MS who take these drugs. Azathioprine is still used in
patients with neuromyelitis optica, and neurologists should be
cautious with this population, said Jonathan Howard, MD, of New
York University, who was not involved with the study.
Mitoxantrone and azathioprine are also more commonly used in
patients with rheumatologic disorders, particularly rheumatoid
arthritis, and other conditions of unknown etiology like
sarcoidosis, Wolinsky noted.
Ragonese disclosed financial relationships with Merck Serono,
Biogen, Novartis, Sanofi Genzyme, and Teva.
Co-authors disclosed financial relationships with Boehringer
Ingelheim, Biogen, Teva, Merck Serono, and Novartis.
Reviewed by Henry A. Solomon, MD, FACP, FACC Clinical Associate
Professor, Weill Cornell Medical College and Dorothy Caputo, MA,
BSN, RN, Nurse Planner[/quote]
The article can be seen here
HTML https://www.medpagetoday.com/Neurology/MultipleSclerosis/67263?xid=nl_mpt_DHE_2017-08-15&eun=g345846d0r&pos=1.
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