WASHINGTON--A consortium of 11 cancer centers is in the midst of a phase
I dose-escalation study of carmus-tine in brain cancer patients, using
Guilford Pharmaceutical's Gliadel Wafer as the drug delivery vehicle.
The FDA approved the wafer for the treatment of glioblastoma multiforme
in 1996. It consists of a dime-size biodegradable wafer made of polifeprosan
20 impregnated with carmustine (BiCNU), 3.9%. Seven or eight wafers are
placed in the cavity created by a tumor's removal and release the drug
as they degrade. Most of the drug is delivered within the first few days.
The New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium undertook
the BiCNU escalation trial, in part, because recent animal data suggest
a 20% wafer is much more effective than the 3.9% wafer now in use.
The NABTT recently completed testing a 6.5% BiCNU wafer and has been
cleared by its monitoring committee to begin a trial of a 10% BiCNU wafer.
Eventually the team hopes to reach 20% BiCNU, project leader Stuart
A. Grossman, MD, of the Johns Hopkins Oncology Center, said at a congressional
briefing sponsored by the National Coalition for Cancer Research (NCCR).
Other NABTT Trials
In its first drug test, the NABTT found that the standard dose of paclitaxel
(Taxol), when given to brain tumor patients, failed to cause normal side
effects or offer any real benefit. It turned out, Dr. Grossman said, that
antiseizure medications taken by the patients speeded up the liver's ability
to clear paclitaxel.
In another test, the group found that an investigational drug, 9-amino-camptothecin,
did not cause the expected side effects in patients taking anticonvulsants
when given at a dose of 850 µg/m²/day for three days, the dose
recommended by the National Cancer Institute.
As a result, the NABTT has dose escalated this drug in patients taking
anticonvulsants to 1776 µg/m²/day for three days.
"Maybe the reason these brain tumors have been so hard to treat
is that the drugs have never had a fair trial in patients on anticonvulsants
because of unexpected drug interactions between the chemotherapy drug and
the anticonvul-sants," Dr. Grossman said.