Dr. Arenson's Approach to Treatment
and His Strategy for Cure
2007 party for Dr. Arenson's patients who are long-term survivors
of high-grade brain and spinal tumors. See full story in News
& Events.
Dr. Arenson and his team share the philosophy that aggressive treatment,
with the goal of cure, is the only way to make progress in treatment
of brain and central nervous system (CNS) tumors. This philosophy
is based on the fact that the tumor itself constitutes the greatest
threat to both survival and quality of life and that aggressive
treatment, if successful, even though it might involve risks and
inconvenience, is a far better choice than to follow old or “standard”
treatments that provide only brief tumor control.
High-Grade Tumors
These are the most common and most serious of all central nervous
system tumors. High-grade tumors, which include the diagnoses glioblastoma
multiforme, anaplastic or Grade III astrocytoma, mixed glioma and
high-grade ogliodendroglioma are more aggressive, faster- growing,
surgically incurable and carry a substantially worse prognosis than
low-grade tumors. These tumors most frequently recur at the primary
site very close to the margin of surgery, but may also recur in
more distant locations within the central nervous system. Traditionally,
very few patients with high-grade glioma have survived, despite
treatment with surgery and radiation. The addition of a single chemotherapeutic
agent, such as BCNU or Temodar, adds a few months to the predicted
outcome of 8 to 12 months before tumor progression.
Since it is clear that these tumors are almost never cured with
surgery and radiation and single-agent chemotherapy, we have employed
combination chemotherapy plus a new type of treatment called biological
therapy. Since there is virtually no precedent in human cancers
for cure using single chemotherapeutic agents, we have employed
combinations of drugs with different mechanisms of action in order
to reduce the likelihood of tumor resistance and different side
effects, so that they can be given safely together.
Between 2000 and mid-2002, we treated patients with a protocol
employing the chemotherapeutic agents BNCU, irinotecan and temozolomide,
which we entitled BITE. Forty-three of these patients had a diagnosis
of glioblastoma multiforme, the most severe of all central nervous
system tumors. Of these 43 patients, 26% are still alive, most with
no evidence of active disease. We are hopeful that these patients
will remain disease-free. The median follow-up of these patients
is 30 months and median survival is 24 months, which is substantially
better than results published in the medical literature. In addition,
if those patients with complete or near-complete tumor removal were
singled out, their overall survival would exceed 50%.
Because of these encouraging results, but in an effort to reduce
the occasional excessive toxicity of the BITE regimen, we have now
modified the treatment by substituting the drug Taxol for the BCNU.
BCNU is still used if the initial response is not adequate. This
new regimen, which we call TITE, is showing encouraging results
and is clearly safer than its predecessor, BITE.
An important element of our current treatment plan is to initiate
chemotherapy with two of the three drugs (irinotecan and Temodar)
during radiation instead of waiting for radiation to be completed.
This has been well-tolerated and has clearly reduced the early relapse
rate to less than 5% as compared to the 25 to 30% that would be
expected if chemotherapy were delayed. The rationale for doing this
is to avoid delaying important treatment, provide for possible sensitization
of tumor cells to radiotherapy and to arrest the growth of the tumor
as quickly as possible while waiting for radiotherapy to reach doses
capable of controlling tumor growth.
To the best of our knowledge, this chemotherapy approach is
unique and unavailable anywhere else in the world.
Biological therapy or Biotherapy:
The newest type of cancer treatment, and perhaps the most exciting,
is called biological therapy or biotherapy. This approach utilizes
agents which do not attempt to kill cancer cells and therefore have
fewer side effects and can be continued indefinitely. This provides
a substantial advantage over traditional chemotherapy, which can
be given only for limited periods of time. These treatments change
the chemistry of tumor cells or interfere with their recruitment
of new blood vessels which are necessary for growth. Some of these
agents, which are now commercially available, include Celebrex and
similar drugs, low-molecular weight heparin, thalidomide, tamoxifen
and cis-retinoic acid. Others are expected soon. Since these agents
can be combined with chemotherapy without interference or excessive
side effects, we routinely include one or more of these agents during
the early phases of chemotherapy but intensify the biological treatment
once the intensive chemotherapy has been completed.
Low-Grade Tumors
These tumors include Grade II (rarely Grade I) astrocytoma, oligodendroglioma
and mixtures of the two. They are slower-growing than high-grade
tumors, potentially curable by surgery and carry a substantially
better prognosis. The treatment is controversial.
Surgery: The initial treatment for these tumors is surgical.
Every effort is made to remove the entire tumor. Frequently, however,
this is not possible since low-grade tumors often have been present
for many months or years and have spread to areas of brain where
surgery is unsafe. Therefore, additional treatment may be necessary.
Radiation has been used for many years for the treatment
of unresectable low-grade tumors. Although there is clear evidence
that radiation has a beneficial effect, it is not clear from the
medical literature that radiation therapy is curative. Furthermore,
there is legitimate concern about its long-term effect on brain
health and function. Therefore, we favor avoidance of radiotherapy
unless other measures fail.
Chemotherapy has the advantage of having no or minimal effect
on the brain itself. There are recent reports indicating benefit
of chemotherapy in low-grade tumors using single agents or combinations.
One commonly used combination is called PCV — representing
the drugs procarbazine, CCNU and irinotecan. Although this regimen
is effective, it is not well-tolerated and seldom can be given for
more than six months. There is good reason to believe that adequate
treatment of low-grade gliomas requires longer therapy.
Therefore, we have modified PCV to make it a more tolerable and
perhaps a more effective regimen which we call TCVEP, which we give
for one year. 35 patients have been treated with PCV or TCVEP over
the last six years. Most have not required radiation. 95% of these
patients are currently alive, all but two with no evidence of active
disease.
Summary
For patients who elect to take an aggressive approach to the treatment
of their tumors and are suitable candidates for such treatment,
Dr. Arenson treats with the goal of cure.
Not all patients are candidates for this approach. For those who
are, results are promising and suggest the possibility of long-term
survival for a subset of patients including those with high-grade
tumors.
Because Dr. Arenson is in private practice, treatment can
be individualized to insure the best outcome for each patient. In
addition to newly-diagnosed patients, patients whose treatment has
been given elsewhere are welcome to inquire and frequently can be
helped by Dr. Arenson.
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Almost
six years ago I was diagnosed with an astrocytoma brain tumor. After
surgery the doctor told me that he could not remove the tumor, that
it was still in there. Even worse, he gave me a prognosis of two
to five years. Not satisfied with that answer, or that hospital,
I went in search of a second opinion. Meanwhile, my tumor was growing,
and I needed a new set of treatment options.
