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This is Your Brain on Drugs
 The "Brain
Tumor Drugs": BCNU and CCNU
Intravenous BCNU (also called carmustine)
and its oral cousin CCNU (also called lomustine) have been the mainstay of
chemotherapy treatment for brain tumors for more than twenty years. Both drugs
cross the blood-brain barrier and both cause nausea, vomiting, and low blood
counts, sometimes for several weeks after a single dose. The effect on the bone
marrow, which produces white blood cells, red blood cells, and platelets, may
last for several months, affecting the tolerance to future chemotherapy.
Nevertheless, BCNU and CCNU are components of
many brain tumor protocols. CCNU is one of the agents in a three-drug regimen,
PCV, which also includes the oral drug Procarbazine and the intravenous drug
Vincristine. BCNU has also been used in high-dose therapy with bone marrow
transplant but in high doses, BCNU has caused lung disease. This lung toxicity
has been severe enough to cause death in some patients in remission from their
brain tumor.
How effective are the nitrosoureas? One of the
first studies to demonstrate a benefit for BCNU chemotherapy randomized patients
to radiation therapy following surgery, with or without intravenous BCNU. There
was no difference in the survival in the two groups, except that there were more
patients in the BCNU treated group who achieved 2 year survival. Analyzing
results from 17 clinical trials, Dr. Howard Fine noted a 1 and 2 year survival
advantage in patients treated with nitrosureas and radiation therapy vs.
radiation alone. Treatment with BCNU following radiation therapy is considered
"standard therapy" and many of the clinical trials testing new drugs randomize
patients to receive either the new drug or BCNU following radiation therapy.
CCNU in combination with another oral drug, Procarbazine, is approximately
equivalent to intravenous BCNU.
BCNU is often given as a single intravenous
infusion, once every 6 to 8 weeks, or the dose can be divided over two or three
days, which may lessen the nausea associated with the drug. BCNU has been given
with intra-arterial adminstration, directly into the blood supply of the tumor,
but it is more toxic. Some studies have indicated that intravenous BCNU is both
safer and more effective than intra-arterial BCNU.
Because of the length and severity of the bone
marrow effects, BCNU and CCNU are to be used with caution in combination with
other drugs. However, other drugs, including cisplatin, etoposide, and
temozolomide have been used with BCNU and some studies indicate that the
combinations, although more toxic, may be more effective.
| The "BCNU wafer": Gliadel®
BCNU is the active chemotherapy ingredient
in the Gliadel® wafer, a dissolvable disc that is inserted in the
resection cavity of a tumor.
The total dose in a Gliadel® wafer is only
a few milligrams, but because all of the drug is released into the
surrounding brain tissue, it is still effective at this low dose. Very
tiny amounts of BCNU have been detected in the blood of patients receiving
Gliadel®, and no effect on the lungs or blood cells have been detected. |
Dr. Richard Weiner inserts
Giadel® wafers after the
removal of a glioblastoma. |
|
MRI of inserted
Gliadel® Wafers |
Studies have shown that Gliadel® does improve survival in patients who are
having surgery for recurrent glioblastoma and some preliminary studies
have shown that it is effective with the first resection also.
For further information, you may access
the Gliadel® website at
www.Gliadel.com. |
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