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A
report from Dr. Stewart Goldman, Dr. Maryanne Marymont, Dr.
Tadanori Tomita |
Almost everyone remembers
the tragedy of Thalidomide babies in the late 1950s – children
with severe limb deformities linked to this drug, now known to be
a carcinogen, prescribed as a sedative and used to treat morning
sickness in pregnant women. After rejecting approval of the drug
37 years ago, the FDA has approved the use of Thalidomide combined
with chemotherapy and radiation therapy in a limited site pediatric
trial.
"We believe Thalidomide inhibits the growth of blood vessels,"
said Dr. Goldman. "This is bad for a developing fetus, but
good for combating lesions and tumors."
Researchers at Children’s Memorial developed the Thalidomide
protocol and will serve as the principle institution implementing
the study. Other participating research centers include Memorial
Sloan Kettering Cancer Center, Los Angeles Children’s Hospital
(USC), and the University of Wisconsin. John’s Hopkins University,
Stanford University, and the Royal Children’s Hospital University
of Melbourne (Australia) may participate as well.
The research team at Children’s is also developing a follow-up
study using this same combination of drugs plus an accelerated radiation
schedule. The more intense radiation treatment requires two doses
per day for approximately 20 consecutive days. This regimen compares
with the standard radiation schedule of six weeks.
Doctors theorize that the standard regimen sub-lethally irradiates
tumor cells, which then repair themselves and become resistant
to future radiation treatments. Laboratory research and adult trials
in India suggest that an accelerated radiation schedule will be
more effective than the typical six-week schedule at killing otherwise
resistant tumor cells.
Another emerging technology involves irradiating the inside of a
brain stem glioma. This procedure has not yet been tested on children.
Researchers at Children’s Memorial hope to do a pilot study
on mice to master the technique, and then to move quickly into patient
studies. This form of radiation will allow Dr. Tadanori Tomita to
treat lesions that are not surgically accessible, without systemic
complications.
New drug therapies are on the horizon
 The
research team at Children’s Memorial plans to seek additional
funding for the development of a glucose-based drug to be used as
a radiation-sensitizing agent in treating brain stem tumors. The
drug would also serve to protect normal brain cells from radiation
damage. The study, called Oral 2-Deoxyglucose and Irradiation for
Brain Stem Gliomas, has been proposed to the National Cancer Institute,
but so far no clinical trials have been established.
A new drug developed by a Northwestern University scientist, called
Thrombospondin, will soon begin phase one testing in Europe. Dr.
Perry Nissen, who is overseeing these early trials, has promised
that Children’s Memorial will be the first hospital to use
this new agent to treat pediatric brain tumors. “We do not
have control of the timetable,” said Dr. Goldman, “But
we hope to reach the patient testing stage in the next three years.”
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