DOOR OPENS FOR AGGRESIVE BRAIN CANCER
More advanced imaging allows researchers
to see not only if a drug is working but also how it
is working. Here, a brain tumor distorts white matter
fibers (left). After a month of treatment (right), swelling
around the tumor has receded and the fibers are normalized.
Reduction in swelling was an unexpected benefit that
may hold the key to understanding how cediranib extends
led to dramatic improvements within 24 hours of the first
daily oral dose. I didnt believe it when I first
saw it, Sorensen recalls, but the results were
very consistent and clear. One MRI test monitored the
decreasing vessel leakage. Another showed the overall mass
of tumor and edema shrinking. A third revealed that the brain
pathways disconnected by the tumor reconnected, presumably
restoring brain function.
results translated into clinical benefits, according to the
preliminary results reported in the January 2007 issue of
the scientific journal Cancer Cell. In this study, patients
live longer and their tumors shrink, summarizes Batchelor.
At the three-month point, half the patients noted a 50-percent
shrinkage, and many, like Andrea, benefited even more.
new drugs frequently pose new complications, and Andrea experienced
her share, her feelings remain positive. Ive beaten
the odds with this drug, she acknowledges, thanks
to the support of Cancer Center staff, and my husband, friends
and family, and all the hugs and kisses from my son Dylan.
David, adds, We feel blessed to have had over twelve
extra months so far, and that something wonderful has come
out of this tragedy. In addition, Andrea quickly weaned
herself off the steroids that control swelling, thus escaping
the side effects. Most patients in the trial could also reduce
or stop using steroids entirely.
team anticipated, the tumors eventually became resistant to
the drug, but they had identified a normalization window
of reduced swelling and healthier blood flow. According to
Batchelor, this was the first trial to identify the
onset and duration of a normalization window, which
typically ranged from one month to several months.
the Bench-to-Bedside Loop
the researchers want to test the theory that the normalization
window provides an opportunity for chemotherapy drugs to penetrate
the tumor more effectively and kill the cancer cells. To that
end, they are recruiting glioblastoma patients for two spin-off
trials of cediranib. The first, which is a large international
study opening at nearly 70 sites in the United States, Europe,
Canada and Australia under Batchelors leadership, will
study patients with recurring glioblastoma. The second trial,
which will investigate the efficacy of the drug in newly diagnosed
glioblastoma patients, recently received a substantial grant
from the National Cancer Institute. This study will combine
cediranib, chemotherapy and radiation, and may allow doctors
to take advantage of the normalization window created by cediranib.
The doctors hope that this normalization will improve the
delivery of the oral anti-cancer drug temozolomide and create
other biological changes that allow chemotherapy and radiation
to work better.
trials, the Cancer Center collaborators need to know when
the normalization period is coming to an end, which will signal
that chemotherapy will become less effective. Thanks to the
generosity of an anonymous donor with personal ties to a glioblastoma
patient, they purchased specialized machines that enable them
to find blood molecules, or biomarkers, that indicate when
the tumor begins to become resistant to cediranib. This
is a tremendously useful finding, says Jain. Markers
are important because most hospitals dont have specialized
neuroimaging machines, but anyone can run a blood test.
Back in the lab, Jain is investigating these markers. Hes
also researching other questions raised by the study, including
methods to extend the normalization period. This work
did what trials are supposed to do, concludes Jain.
It spawned new trials and new bench work that will lead
to new treatments. And the effort could benefit many
cancer patients, not just those with glioblastoma. - Cathryrn
the Specialized Care of Individuals with Brain
Brain Tumor Center
Yawkey Building 9th Floor
Boston, Massachusetts, 02114
& Families with questions about referrals, consultations
or appointments may contact:
questions may contact:
Tracy Batchelor, M.D.
MGH Brain Tumor Center