For Medical Professionals
Dr. Arenson Presents Paper on Chemotherapy Treatment
for Low-Grade Gliomas
to American Society of Clinical Oncology
Abstract of Paper:
Use of modified PCV chemotherapy as principal therapy for adults
with incompletely resected or recurrent low-grade glioma: A retrospective review
EB Arenson, J Bank, M Pierick, C Greenwald, J McVicker, JP Elliott,
JD Day, TM Fullagar; The Colorado Neurological Institute, Englewood,
Colorado
Background: In order to assess outcomes of patients treated
with chemotherapy versus a more standard approach of radiotherapy
(RT), we reviewed 48 patients with newly diagnosed, partially resected
or recurrent low-grade glioma (LGG) treated between 1996 and the
present.
Methods: Patients were divisible into three groups: those
treated with chemotherapy + RT before (Group A, 28 patients) or
after (Group B, 13 patients) radiographic progression, and those
with recurrences after treatment with RT (Group C, 7 patients).
Diagnoses included astrocytoma (23%), oligodendroglioma (48%) and
mixed glioma (29%). 39 patients were treated with chemotherapy alone
and 9 received post-chemotherapy RT. Chemotherapy consisted of PCV
in one case; all other patients received modified PCV (MPCV), which
variably included addition of carboplatin (200-360 mg/m2) and etoposide
(150 mg/m2) and substitution of temozolomide (150 mg/m2/day x 5
doses) for procarbazine. The intent was to treat monthly for one
year.
Results: Patients received a mean of 10 courses of MPCV;
481 cycles were given. There were no deaths or admissions during
chemotherapy. Grade III/IV toxicities occurred in 108 cycles (25
patients), 107 hematologic and 1 GI. Late effects included 1 case
of MDS and 1 AML. There were no cases of disease progression during
chemotherapy. Two patients stopped MPCV early, one because of worsening
seizures (2 cycles) and one by personal preference (1 cycle); both
died of disease. With a median follow-up of 46 months (range 4-120)
from initiation of chemotherapy, overall survival and progression-free
survival were 89% and 79% for Group A, 91% and 83% for Group B,
and 100% and 86% for Group C. Of 6 patients (12.5%) who recurred
after completing chemotherapy, 2 have died; both had received post-chemotherapy
RT and had clinical features of GBM. Four patients are either lost
to follow-up (2) or alive with stable disease (2) following additional
treatment.
Conclusions:
- MPCV is a tolerable regimen which can be given more aggressively
than standard PCV.
- There is minimal risk of early disease progression with MPCV.
- Results support a prospective trial comparing MPCV to RT in
patients with progressive unresectable LGG, and use of MPCV as
salvage therapy for patients who fail RT.
Dr. Arenson Presents Promising Chemotherapy Results
at International Neuro-oncology Conference
On May 7, 2005, Dr. Edward Arenson presented a paper
at the 2nd Quadrennial Meeting of the World Federation of Neuro-oncology
(WFNO), 6th Meeting of the European Association for Neuro-oncology,
in Edinburgh, Scotland. Below is the abstract of his paper:
Encouraging results for a novel chemotherapeutic regimen in
newly diagnosed glioblastoma multiforme, Arenson, E., Bank,
J., Pierick, M., Greenwald, C., Fullagar, T., and McVicker, J. from
the Colorado Neurological Institute and Swedish Medical Center,
Englewood, CO, USA.
Substantial benefit from chemotherapy of cancer requires effective
combinations; nevertheless, monotherapy with temozolomide (TMZ)
has emerged as the “standard” treatment of glioblastoma
multiforme (GBM). We report results of treatment of GBM with the
novel combination of BCNU, irinotecan (CPT11) and TMZ (BITE). Four
patients were excluded from this treatment because of: expected
survival < 3 months, absence of caregiver or 24 hour care requirement.
Thirty-seven patients with newly diagnosed GBM were treated between
August, 1999 and October, 2002. Mean age was 53.4 years. Thirteen
patients had bilateral and/or multifocal disease. Nine had gross
total resection, 27 subtotal resection and 1 biopsy, as determined
by early post-operative contrast MRI. Treatment consisted of three
courses of CPT11 (400 mg/m2 x 1) and TMZ (200 mg/m2 x 5) given every
21 days during standard radiotherapy (RT) (phase I) to which BCNU
(40 mg/m2 x 3) was added after RT for up to 6 monthly courses as
tolerated (phase II). Three patients did not complete phase I because
of patient choice, neurological decline or death from intratumoral
hemorrhage unrelated to treatment. Two additional patients did not
proceed to phase II because of poor performance status. Thirty-two
patients received 115 courses of BITE (mean 3.4) and had episodes
of grade III/IV toxicities as follows: GI 12%, neutropenia 42% and
thrombocytopenia 11%. There were 2 deaths during phase II unrelated
to disease progression: one disseminated CMV and one bacterial pneumonia.
One patient survived an atypical mycobacterial pneumonitis, and
one survived an episode of BCNU pneumonitis. With minimum follow-up
of 30 months, mean survival is 19 months. Overall survival is 59%
1-year, 30% 2-year, 19% 3-year, and relapse-free survival is 46%
1-year, 22% 2-year and 11% 3-year. Six patients are alive (16%),
five without evidence of disease and one with stable disease from
37 to 48 months post diagnosis. For patients with initial gross
total resection (24%), relapse-free survival was 67% 1-year, 33%
2-year and 11% 3-year. We conclude that: 1. BITE is toxic, but effective
2. polychemotherapy should not be abandoned in GBM 3. BITE deserves
further study with efforts to reduce toxicity 4. patients with gross
total resection may survive long-term with aggressive post-surgical
treatment.
Dr. Arenson's Brain Tumor Program
Praised by Dr. Raymond Sawaya, Chairman, Dept. of Neurosurgery
M. D. Anderson Cancer Center
During a recent visit to Dr. Arenson's
offices, which included considerable time spent talking with
staff and patients, Dr. Sawaya expressed high regard
for Dr. Arenson's program, especially its multi-disciplinary
team and patient-centered approach to treatment. During his
brief stay in Denver, Dr. Sawaya also delivered the annual
Neuro-Oncology Lecture attended by Colorado Neurological Institute
and Swedish Medical Center medical and nursing staff.
Dr. Arenson Publishes
Two Articles in the CNI REVIEW Medical Journal
 The
Summer 2004 issue of CNI's medical journal, CNI REVIEW,
is dedicated to discussing the issues related to treatment
of brain and central nervous system tumors. As medical director
of the CNI Center for Brain & Spinal Tumors, Dr. Arenson
contributed two of the articles for this issue.
Below are the abstracts of Dr. Arenson's articles
with links to the full text in PDF format. Click the icon
or title to view the full article. You can also go to the
CNI
website to read the entire issue.
Neuro-oncology:
The Promiscuous Discipline 
The relatively new field of neuro-oncology has arisen in
response to the long overdue surge in interest in central
nervous system (CNS) tumors by health care professionals.
Since this field has no history or tradition, its definition
remains elusive. What is clear is that the field concerns
itself with the care (mostly postsurgical) of patients with
CNS tumors. A neuro-oncologist typically assumes full responsibility
for the care of patients with CNS tumors following surgery
if ongoing care is necessary. Certainly all patients with
malignant CNS tumors, low-grade or high-grade, completely
or partially resected, should be followed by a neuro-oncologist.
In addition, patients with benign tumors complicated by ongoing
issues such as seizures, functional impairment, or significant
comorbidities frequently benefit from the care of a neuro-oncologist
who essentially becomes the primary care physician for issues
related to the tumor.
Chemotherapy
for Brain Tumors: Current Status and Controversy
The current status of chemotherapy for primary malignant
tumors of the central nervous system (CNS) is controversial
and complex. Despite the fact that it is well known in the
oncology community that cancer is virtually never cured with
single agent chemotherapy (monotherapy), the current “standard”
treatment for glioblastoma, the most lethal of all CNS tumors,
is single agent temozolomide (TMZ). This relatively new drug
has the advantage of being an oral agent, relatively low toxicity
profile and crossing the blood-brain barrier. Furthermore,
it is easy for oncologists to give. A recent study has clearly
demonstrated that survival is improved (3 months) if this
drug is given both during and after radiation therapy. However,
the disease remains essentially incurable with this approach.
The principle argument against using TMZ in combination with
other drugs is that, thus far, studies have not established
the safety and efficacy of such combinations.
Dr. Victor Levin
of M. D. Anderson
Speaks at CNI's Annual Memorial Lectureship
The Colorado Neurological Institute’s Center for Brain
and Spinal Tumors (of which Dr. Arenson is medical director)
held its Annual Memorial Lectureship for both the public as
well as health care professionals. Our guest was Dr. Victor
Levin, professor of Neuro-oncology at M. D. Anderson Cancer
Center in Houston, Texas. Dr. Levin was the 6th recipient
of our annual Award for Excellence in Neuro-oncology.
He lectured on current progress in the molecular biology
of central nervous system tumors and new strategies for therapy.
He also participated in our multi-disciplinary neuro-oncology
conference on Friday morning and rounded with the Brain Tumor
Team. Dr. Levin was very impressed with our Program and wrote
us the following letter after returning to Houston.
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