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(Drug information on 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(Drug information on 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.