SEATTLE, Jan. 23 /PRNewswire/ -- Gastrointestinal graft-vs.-host
disease is a common and potentially deadly side effect for patients who
undergo an allogeneic stem-cell transplant to treat certain blood cancers.
Now, new research from Fred Hutchinson Cancer Research Center shows that
adding a widely used topical corticosteroid to the standard treatment for
GVHD kept the disease in remission and significantly reduces deaths one
year after therapy.
A reformulation of beclomethasone dipropionate (BDP) into two different
pills specifically releasing the drug into the stomach and mid-small
intestine prevented relapse of gastrointestinal GVHD and allowed those
patients to be on a shorter treatment course of high-dose prednisone.
Mortality was reduced by 46 percent a year following the start of treatment
in a multi-center Phase III clinical trial, according to findings published
today in the online edition of the journal Blood. The lead author is David
M. Hockenbery, M.D., a member of the Clinical Research Division at the
Hutchinson Center and a professor of medicine/gastroenterology at the
University of Washington School of Medicine.
BDP is an anti-inflammatory drug long used to treat a variety of
diseases such as asthma and ulcerative colitis.
About 60 percent of patients who receive an allogeneic stem-cell
transplant to treat blood cancers such as acute and chronic myelogenous
leukemia, acute lymphocytic leukemia and non-Hodgkin's lymphoma develop
gastrointestinal GVHD as a major side effect of being infused with donor
stem cells. Those who show gastrointestinal symptoms of the disease usually
receive a two to four-week course of high-dose systemic prednisone therapy
that is then tapered slowly. However, that drug is a two-edged sword,
Hockenbery said. On the one hand it is designed to suppress the donor cells
so GVHD can be controlled. But suppressing the immune system also makes
patients susceptible to potentially fatal infections.
In the clinical trial, 129 patients were randomized into two groups.
One group received a short course of standard prednisone therapy and oral
BDP for 50 days. The other group received a placebo in place of the oral
BPD for the same period. At day 10, the prednisone dose was quickly tapered
in patients whose symptoms had responded. Fewer patients randomized to BDP
had a subsequent flare-up of GVHD. After completion of the 50-day treatment
period, patients were followed for an additional 30 days to see if the
treatment effect would last. Patients randomized to BDP had a significantly
more durable response rate compared to those in the placebo group. At one
year after treatment, mortality rates had been reduced 46 percent compared
to the placebo group.
"Oral BDP provides much more tailored and targeted control of
gastrointestinal GVHD and it allows patients to move away from the side
effects of standard prednisone therapy. All of this improves the chances
that patients will have a successful outcome," Hockenbery said. "I think
this is a very convincing clinical trial because by targeting topical
therapy to the areas most affected, we were able to keep symptoms at bay
while minimizing systemic immune suppression."
The idea to reformulate BDP into an oral form for stem-cell-transplant
patients belongs to George B. McDonald, M.D., one of the study co-authors
and a colleague of Hockenbery's at the Hutchinson Center. McDonald, also a
member of the Center's Clinical Research Division and a professor of
medicine/gastroenterology at UW, initiated the early trials of oral BDP
with funding from a U.S. Food & Drug Administration Orphan Products
Development Grant. The goal was to target corticosteroid therapy to the
areas of the GI tract affected by GVHD. The anti-inflammatory actions of
the two BDP- containing pills would then be focused on the intestinal
lining from top to bottom to suppress GVHD, thus avoiding excessive
corticosteroid medication in the bloodstream.
The FDA is expected to decide whether to approve use of the oral form
of the drug by July. If approved, it would be only the second drug approved
by the FDA for treatment of GVHD in stem-cell transplant recipients.
The pivotal clinical trial was funded by an Orphan Products Development
Grant of the U.S. Food & Drug Administration and by Enteron Pharmaceuticals
Inc., a wholly-owned subsidiary of DOR BioPharma Inc. Fifteen other centers
in the U.S. and France participated in the study.
At Fred Hutchinson Cancer Research Center, our interdisciplinary teams
of world-renowned scientists and humanitarians work together to prevent,
diagnose and treat cancer, HIV/AIDS and other diseases. Our researchers,
including three Nobel laureates, bring a relentless pursuit and passion for
health, knowledge and hope to their work and to the world. For more
information, please visit fhcrc.org.
Conflict of interest disclosure: George McDonald, M.D., is a consultant
for Enteron Pharmaceuticals Inc. and has an equity position in the company.
CONTACT
Dean Forbes
206-667-2896
dforbes@fhcrc.org
SOURCE Fred Hutchinson Cancer Research Center
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Related links:
http://www.fhcrc.org/
CONTACT:
Dean Forbes of Fred Hutchinson Cancer
Research Center, +1-206-667-2896, or dforbes@fhcrc.org
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