Johns Hopkins Gazette: May 1, 1995

Brain Tumor Therapy May Prolong Life

By John Cramer

     Scientists at Johns Hopkins report that a brain tumor
treatment which delivers an anti-cancer drug in a time-release
fashion from surgically implanted biodegradable polymer discs has
proved its value in prolonging the lives of some dying patients.
Results of the study on 222 patients at 27 hospitals are reported
in the April 22 issue of The Lancet.

     "The treatment should greatly change conventional therapy
for brain tumors and possibly cancers in other organs," says
study author Henry Brem, director of neurosurgical oncology at
the Medical Institutions. "Although the trials were conducted
with patients with advanced tumors with this study, we can say
the new treatment may be a more logical part of initial therapy,"
Dr. Brem added. "This will be relevant for practical treatment
immediately, not 20 years from now, and it's exciting because it
opens the door for further uses."

     There are an estimated 20,000 brain cancer surgeries
performed each year in the United States. Dr. Brem anticipates
that the biodegradable polymer disc could be the treatment of
choice for as many as 40 percent of those patients within three
years after FDA marketing approval.

     The new polymer-drug combination system is currently under
FDA review.

     Among the patients with brain tumors, study results showed
median survival rates of 31 weeks for 110 patients receiving
carmustine (BCNU) saturated polymers compared to 23 weeks for 112
patients getting placebo polymers, a 34 percent improvement in
survival time.

     For patients with glioblastoma multiforme, the most common
and severe tumor, results were even better, Dr. Brem said.
Six-month survival was 50 percent higher in patients receiving
the BCNU-polymers than in those treated with placebo polymers.

     Moreover, the BCNU-polymers produced no significant side
effects, and the patients' quality of life was good, Dr. Brem

     The main targets of the polymer technique are malignant
gliomas, the most common form of malignant brain tumor, which are
highly lethal and conventionally treated with surgery followed by
radiation therapy and/or chemotherapy. Other brain diseases, as
well as cancers needing central nervous system treatment, may in
the future be treated by these controlled-delivery polymers.

     The Lancet report confirms preliminary findings that Dr.
Brem presented in 1994 describing earlier controlled trials of
the polymer wafers. 

     For 10 years, Dr. Brem has been investigating this new way
of delivering drugs against brain tumors as an alternative to
conventional chemotherapy, in which the whole body or a region is
exposed to large amounts of drugs, causing severe side effects.
Moreover, only trace amounts reach the brain in conventional
treatment because of the blood-brain barrier, which protects the
brain from chemical fluctuations by restricting the entry of
molecules, including drugs aimed at brain tumors.

     The new study evaluated 222 patients with recurrent
malignant brain tumors at 27 hospitals which make up the
Polymer-Brain Treatment Group. Patients were randomly assigned to
receive the dime-size discs with or without BCNU. After the
tumors were surgically removed, the discs were put into the
resulting cavity to deliver small amounts of medication to the
tumor bed in a sustained-release fashion to destroy any remaining
cancer cells. 

     "This is the first full demonstration that localized drug
therapy [vs. traditional chemotherapy] is safe and effective in
prolonging life in these patients with brain tumors," Dr. Brem
said. "It's proof that controlled-release polymers work."

     Researchers at Hopkins continue to look for the most
effective drugs for use in the polymers, which dissolve at a
controllable rate. Dr. Brem has published four articles in the
past year on animal research with promising results against brain
cancer with the drugs taxol, the anti-angiogenic antibiotic
minocycline, 4-hydroperoxycyclophosphamide (4HC) and

     These drugs were ineffective when given systemically by
traditional injection, but were highly effective when delivered
with polymers directly to the brain. Thus, the polymers may allow
these drugs to be used for treating brain tumors. Early safety
testing in people may start in the fall at Hopkins.

     The five-year Lancet study was funded by grants from the
National Cancer Institute and Guilford Pharmaceuticals, Inc.,
which is developing the polymers for therapeutic applications.
The company, based in Baltimore, plans to file an application
with the Food and Drug Administration for marketing approval
within the next year. The study was based on a collaborative
effort between Hopkins and the Massachusetts Institute of
Technology, where a biodegradable polymer that can release drugs
was invented.

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