This is Your Brain on Drugs
CPT-11:
It's Not Just for Colon Cancer Anymore
 What
is CPT-11?
CPT-11, also known as irinotecan, trade name Camptosar®, belongs to a relatively
new class of drugs, camptothecins, which are topoisomerase I inhibitors. Cousins
of CPT-11 include topotecan (Hycamptin®) which is used for ovarian cancer, and
9-aminocampthothecin. In 1996 the FDA approved CPT-11 for patients with colon
cancer who had failed other chemotherapy.
CPT-11 and the other camptothecins appear to
interact with an enzyme called topoisomerase I, which causes reversible breaks
in the DNA of a cell. The camptothecins form a complex with DNA and
topoisomerase I and cause irreversible breaks in the DNA. It is the irreversible
breaks in the DNA which account for the death of tumor cells in patients treated
with CPT-11, but also account for its side effects.
CPT-11 is only available in an intravenous
formulation.
 Why
is CPT-11 used in the treatment of brain tumors?
CPT-11 was originally approved for use in the treatment of colon cancer, but
Dr. Henry Friedman of Duke University Medical Center noted that more than fifty
percent of patients with anaplastic astrocytoma and glioblastoma multiforme
appeared to have shrinkage or stabilization of their tumor after treatment with
CPT-11. He noted that some patients tolerated the usual doses given to colon
cancer patients with no side effects at all. He reasoned that the other drugs
taken by these patients (anticonvulsants and steroids) may have affected the
drug levels in the blood.
Since that time, a number of other centers
around the country have used CPT-11 in a wide range of doses and schedules. Some
patients do tolerate doses several times those recommended for colon cancer
patients. At this time, it is not clear whether there is a single "best" dose
that can be recommended. Nor it clear whether the drug
should be repeated weekly, every other week, or every three weeks. There has
even been one study which used low doses daily for two weeks.
What are the side effects of CPT-11?
Nausea, vomiting, fatigue, and diarrhea are commonly seen during treatment
with CPT-11. Some patients also develop low blood counts, particularly the white
blood cell count (leukopenia), and the red cell count (anemia). Diarrhea can be
treated with over-the-counter or prescription medication, but can be severe
enough to cause dehydration. CPT-11 also frequently causes hair loss.
Who should receive CPT-11?
CPT-11 is not yet FDA-approved for the treatment of malignant brain tumors,
but there is interest in pursuing this indication based on Dr. Friedman's
results. At the present time, most physicians are not using CPT-11 to treat
malignant glioma because there are other drugs which are approved, including
Temodar, CCNU, and BCNU. Patients who have taken these drugs may be offered
treatment with CPT-11 if their tumor seems to be resistant to the other drugs.
Because CPT-11 is chemically very different from the other drugs, it is still
possible to respond to CPT-11 even when the other drugs have not seemed to work.
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