Dear New MS
Patient:
When you are
first diagnosed with MS, Doctors are likely to tell you there is nothing
they can do for you - or they will prescribe Avonex, Copaxone, or
Betaseron, none of which can help slow deterioration due to MS.
There is no
treatment approved by the FDA which will make you better, or prevent
deterioration.
However there
is a lot known and you must
take responsibility for your life. Read about Mitoxantrone.
Very Good results!
Multiple
Sclerosis Information: updated
1-06-2000
What follows
is the latest - as of 10-10-97- abstracts on Mitoxantrone and MS:
In particular
read the last article, By Kornhuber. You will learn that the dose is
crucial, and they have figured it out. A smaller dose makes for less
effectivity.
Randomized
placebo-controlled trial of Mitoxantrone in Relapsing/Remitting Multiple
Sclerosis: 24-month clinical and MRI outcome
Millefiorini E, Gasperini C, Pozzilli C,
D'Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo
A, Bernini ML, Gambi D, Prencipe M
J Neurol 1997 Mar;244(3):153-159
Dept. of Neurological Science, Universita' La Sapienza, Rome, Italy
We
designed a randomized, placebo-controlled, multicentre trial involving
51 Relapsing/Remitting Multiple Sclerosis patients to determine the
clinical efficacy of Mitoxantrone treatment over 2 years.
Patients
were allocated either to the Mitoxantrone group (27 patients receiving
I.V. infusion of Mitoxantrone every month for 1 year at the dosage of 8
mg/m2) or to the placebo group (24 patients, receiving I.V. infusion of
saline every month for 1 year) using a centralized randomization system.
Disability
at entry and at 12-24 months was evaluated by four blinded Neurologists
trained in the application of the Kurtzke Expanded
Disability Status Scale (EDSS).
In
addition, the number and clinical characteristics of the exacerbations
over the 24 months were recorded by the local investigators.
MRI,
at 0, 12 and 24 months, was performed with a 0.2 T permanent unit. MRI
data were analysed by two blinded NeuroRadiologists. All patients
underwent a clinical evaluation.
A
statistically significant difference in the mean number of exacerbations
was observed between the Mitoxantrone group and placebo group both
during the 1st and the 2nd year.
Although
there was no statistically significant benefit in terms of mean EDSS
progression over 2 years, the proportion of patients with confirmed
progression of the disease, as measured by a one point increase on the EDSS
scale, was significantly reduced at the 2nd year evaluation in the
Mitoxantrone group.
Forty-two
(23 Mitoxantrone, 19 placebo) patients underwent all MRI examinations
during the 24-month period. We observed a trend towards a reduction in
the number of new lesions on T2-weighted images in the Mitoxantrone
group.
Our
study suggests that Mitoxantrone might be effective in reducing disease
activity, both by decreasing the mean number of exacerbations and by
slowing the clinical progression sustained by most patients after 1 year
from the end of treatment.
Therapeutic effect of
Mitoxantrone combined with MethylPrednisolone in Multiple Sclerosis: a
randomised multicentre study of active disease using MRI and clinical
criteria
Edan G, Miller D, Clanet M, Confavreux C, Lyon-Caen O, Lubetzki C,
Brochet B, Berry I, Rolland Y, Froment JC, Cabanis E, Iba-Zizen MT,
Gandon JM, Lai HM, Moseley I, Sabouraud O
J Neurol Neurosurg Psychiatry 1997 Feb;62(2):112-118
Department of Neurology, Centre Hospitalier Universitaire, Rennes,
France
Objective
To evaluate the efficiency of Mitoxantrone in Multiple Sclerosis.
Methods
Forty two patients with confirmed Multiple Sclerosis, selected as having
a very active disease on clinical and MRI criteria were randomised to
receive either Mitoxantrone (20 mg intravenously (IV) monthly) and
MethylPrednisolone (1 g iv monthly) or MethylPrednisolone alone over six
months.
In
the Steroid alone group five patients dropped out due to severe
exacerbation.
Results
Blinded analysis of MRI data showed significantly more patients with no
new enhancing lesions in the Mitoxantrone group compared with the
Steroid alone group, (90% v 31%, P < 0.001).
In
the Mitoxantrone group there was a month by month decrease almost to
zero in the number of new enhancing lesions, and in the total number of
enhancing lesions, whereas both remained high in the Steroid alone
group.
The
differences were significant for both indices at all months from 1-6.
Unblinded
clinical assessments showed a significant improvement in change in EDSS
at months 2-6 in the Mitoxantrone group, with a final mean improvement
of more than one point (-1.1 v + 0.3; P < 0.001).
There
was a significant reduction in the number of relapses (7 v 31; P <
0.01), and an increase in the number of patients free of exacerbation
(14 v 7; P < 0.05).
Conclusion:
In this selected group of patients with Multiple Sclerosis with very
active disease, Mitoxantrone combined with MethylPrednisolone was
effective in improving both clinical and MRI indices of disease activity
over a period of six months whereas MethylPrednisolone alone was not.
Further
double blinded long term studies are needed to properly evaluate the
effect of Mitoxantrone on progression in disability.
Noninvasive assessment
of
Mitoxantrone CardioToxicity in Relapsing/Remitting Multiple Sclerosis
De Castro S, Cartoni D, Millefiorini E, Funaro S, Gasperini C,
Morino S, Tallarico D, Beni S
J Clin Pharmacol 1995 Jun;35(6):627-632
Department of Clinical Medicine, La Sapienza University of Rome, Italy
Multiple
Sclerosis is the most common cause of Neurologic Disability in young
adults. Recent reports have suggested that Mitoxantrone might be a
candidate for clinical trials in Multiple Sclerosis patients.
The
authors studied 20 patients with Relapsing/Remitting Multiple Sclerosis
to evaluate cardiac toxicity during a one-year follow-up period.
Patients were divided into 2 groups: group A, Mitoxantrone treated
patients (cumulative dose of 96 mg/m2); group B, placebo patients.
The
clinical course of Multiple Sclerosis was assessed using the Expanded
Disability Status Scale and the number
of relapses during the follow-up.
Each
patient had an ElectroCardiogram and a spectral and color flow Doppler
EchoCardiographic examination at enrollment, and 6 and 12 months later,
to investigate cardiac toxicity. The mean exacerbation rate was reduced
significantly in group A patients.
No
significant differences in the ElectroCardiograms or the
EchoCardiographic parameters of systolic and diastolic function were
noted between the two groups or in group A during the follow-up.
Mitoxantrone
treatment seems able to improve the clinical course of
Relapsing/Remitting Multiple Sclerosis patients. It does not show any
Cardiac Toxicity in selected patients at this dosage.
Serial
Gadolinium-enhanced MRI in patients with Multiple Sclerosis treated with
Mitoxantrone
Krapf H, Mauch E, Fetzer U, Laufen H, Kornhuber HH
Neuroradiology 1995 Feb;37(2):113-119
Department of Neurology, University of Ulm, Germany
Serial
Gadolinium (Gd)-enhanced Magnetic Resonance Imaging (MRI) was used to
monitor the effect of Mitoxantrone in ten patients with rapidly
deteriorating Multiple Sclerosis (MS).
MRI
was performed as a baseline and thereafter at 1, 3, 6, 9, 12 and 24
months. The total number of Gd-enhancing lesions diminished from 169 at
baseline to 10 after 1 year and to 5 after 2 years.
This
reduction and the percentage of follow-up MRI studies showing no Gd
enhancement were more pronounced than in other MRI studies of the
natural course of MS.
Measured
with quantitative Neurological Scales, only one patient showed
deterioration after 2 years; nevertheless, the changes in MRI were much
more marked than those observed clinically.
Serial
Gd-MRI therefore, seems necessary for documenting efficacy in future
therapeutic trials.
A controlled trial of
Mitoxantrone in Multiple Sclerosis: serial MRI evaluation at one year
Bastianello S, Pozzilli C, D'Andrea F, Millefiorini E, Trojano M,
Morino S, Gasperini C, Bozzao A, Gallucci M, Andreula C, et al
Can J Neurol Sci 1994 Aug;21(3):266-270
Chair of Neuroradiology, University of Rome La Sapienza, Italy
We
present the results of a randomized double-blinded placebo controlled,
multicenter trial, of low-dose Mitoxantrone (MX), after one year, in 25
patients with Relapsing/Remitting Multiple Sclerosis, who had serial
enhanced Magnetic Resonance Imaging (MRI).
Treatment
groups were balanced for age, gender, duration of illness and
Neurological disability. Five of the 13 MX patients and 10 of the 12
placebo patients had exacerbations during treatment (p < 0.02).
The
mean change in the Expanded
Disability Status Scale was not
significantly different between the MX and placebo treatment groups.
Serial
Gadolinium-DTPA enhanced MRI detected no significant difference between
the MX treated and placebo groups in the mean total number of new,
enlarging, or Gadolinium-DTPA
enhancing lesions; there was a trend toward a reduction of new,
enlarging and Gadolinium-DTPA enhancing lesions in MX patients.
Despite
this ameliorating effect, the results indicate that serial Gadolinium-DTPA
enhanced MRI, performed over one year in a limited number of patients,
could not provide conclusive evidence for a role of MX therapy in
Relapsing/Remitting Multiple Sclerosis.
ImmunoSuppressive
therapy of Multiple Sclerosis with Mitoxantrone
Mauch E, Kornhuber HH Fortschr
Neurol Psychiatr 1993 Dec;61(12):410-417
Abteilung Neurologie, Universitat Ulm
Preliminary
clinical results indicate that the cytostatic agent Mitoxantrone is an
effective and very tolerable substance for treating Multiple Sclerosis (MS).
Our
own experience, added to the findings of other pilot studies, seems to
indicate that disease progression can be slowed in a majority of
patients with rapidly Progressive MS.
Mitoxantrone
is mainly excreted by the Hepato-Biliary Pathways and therefore it can
be used in patients with Renal Insufficiency or chronic Cystopyelitis, a
frequently occurring condition in MS.
The
side effects observed in our therapeutic scheme which could be
attributed to Mitoxantrone were tolerable.
Mild
GastroIntestinal complaints were occasionally reported and vomiting was
very rare. A CarcinoGenic effect from Mitoxantrone has not been
reported.
A
decrease in the Leucocyte count is to be expected 6-15 days following
treatment administration. Potential CardioToxicity represents the
primary long term adverse reaction and thus patients with CardioVascular
risk factors should not be treated with Mitoxantrone.
Once
a cumulative dosage of 140 mg/m2 is reached Cardiac Function Tests,
including EchoCardiography with measurement of the Left Ventricular
ejection fraction, should be routinely carried out preceding each
treatment administration in all patients.
Mitoxantrone
is currently not licensed for use in patients with MS and therefore
should be restricted to patients with rapid disease progression where
other generally accepted treatment modalities have failed.
An open-trial
evaluation of Mitoxantrone in the treatment of Progressive MS
Noseworthy JH, Hopkins MB, Vandervoort MK, Karlik SJ, Lee DH, Penman
M, Rice GP, Grinwich KD, Cauvier H, Harris BJ, et al
Neurology 1993 Jul;43(7):1401-1406
Department of Clinical Neurological Sciences, University of Western
Ontario, London, Canada
We
treated 13 patients with Progressive MS with Mitoxantrone. All patients
received a standard IV dose of Mitoxantrone (8 mg/m2) every 3 weeks for
a total of seven infusions, with dosage adjustments depending on the
Hematologic profile at the nadir.
The
treatment was well tolerated, with the most common side effect being
mild Nausea. Four of seven women developed transient secondary
Amenorrhea.
The
postenrollment clinical behavior of these patients was generally more
favorable than during the 18 months prior to enrollment (only three of
13 patients developed an increase in the Expanded
Disability Status Scale of more than 0.5 points).
Suggesting
a possible treatment effect, but comparison with two historical control
groups (both the active and placebo groups from the Canadian Cooperative
Trial of Cyclophosphamide and Plasma Exchange) does not suggest that
Mitoxantrone was efficacious.
Eight
of 12 patients had evidence of MRI activity on 13 of 29 follow-up
visits. This small, open-labeled pilot study did not provide strong
support for proceeding with a randomized, controlled trial of this
dosage regimen of Mitoxantrone in patients with Progressive MS.
***Below
is the most important article
***
Treatment
of Multiple Sclerosis
with Mitoxantrone
Mauch E, Kornhuber HH, Krapf H, Fetzer U,
Laufen H
Eur Arch Psychiatry Clin Neurosci 1992;242(2-3):96-102
Department of Neurology, Ulm University, Dietenbronn/Schwend, Federal
Republic of Germany
Ten
Multiple Sclerosis patients, all with a rapid deteriorating disease
profile, were treated with 12 mg/m2 of the cytostatic agent
Mitoxantrone, administered every 3 months.
This
dosage is only 25% of what a patient with a solid tumour would normally
receive during the same time period.
In
all treated patients the deterioration
was stopped following the initial dosage;
in four out of ten patients there was even an immediate improvement of
the Neurological status.
Eight
out of nine patients showed an improvement after 1 year as compared with
their enrollment status; the other one remained stable.
In
correlation with the clinical improvement, the mean P100 latencies of
visual evoked potentials showed a reduction after 1 year.
However,
the changes identified through Magnetic Resonance Imaging were even
clearer than those seen clinically.
At
admission, this group of patients presented with a total of 169
gadolinium (Gd)-enhancing lesions. Only 10 lesions were enhancing in
nine patients 12 months after the initiation of treatment.
It
appears that Mitoxantrone accelerates the disappearance of Gd-enhancing
lesions and prevents the development of new ones.
Minimal
side effects such as mild nausea and a slight faintness were evident in
six patients and then for only 1-2 days.
Currently
there are multicenter Trials in Germany, Belgium, and France, using
Mitoxantrone. The German tests are due to be completed in 1997.
The
medicine is being given at 12 mg/ m sq or 5 mg/m sq, or placebo. Dr. B.
Storch, at Heidelberg U. is leading the German effort.
Dr. Roy
Swank,( who has treated over 3000 MS patients) in his book, "
the Multiple Sclerosis Diet Book",
concludes that a low fat diet, supplemented by the Essential Fatty
Acids, is essential for slowing progress of the disease.
He also
recommends avoiding heat (like Jacuzzi's, hot baths and sunbathing),
resting in a flat position every day to let the body cool, avoiding and
eliminating stress, and getting exercise.
Swimming
and pool exercises are best because your body will not overheat while
exercising.
