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Phase
II trial of the antiangiogenic agent thalidomide in patients with recurrent
high-grade gliomas
Fine
HA, Figg WD, Jaeckle K, Wen PY, Kyritsis AP, Loeffler JS, Levin VA, Black PM,
Kaplan R, Pluda JM, Yung WK
Center
for Neuro-Oncology, Dana-Farber Cancer Institute, and Departments of Neurology,
Surgery, and Radiation Oncology, Brigham and Women's Hospital, Harvard Medical
School, Boston, MA, USA.
Purpose.
Little progress has been made in the treatment of adult high-grade gliomas over
the last two decades, thus necessitating a search for novel therapeutic
strategies.
Malignant gliomas are vascular or angiogenic tumors, which leads to the
supposition that angiogenesis inhibition may represent a potentially promising
strategy in the treatment of these tumors.
We present the results of a phase II trial of thalidomide, a putative inhibitor
of angiogenesis, in the treatment of adults with previously irradiated,
recurrent high-grade gliomas.
Patients
and Methods. Patients with a histologic diagnosis of anaplastic mixed glioma,
anaplastic astrocytoma, or glioblastoma multiforme who had radiographic
demonstration of tumor progression after standard external-beam radiotherapy
with or without chemotherapy were eligible.
Patients were initially treated with thalidomide 800 mg/d with increases in dose
by 200 mg/d every 2 weeks until a final daily dose of 1,200 mg was achieved.
Patients were evaluated every 8 weeks for response by both clinical and
radiographic criteria.
Results.
A total of 39 patients were accrued, with 36 patients being assessable for both
toxicity and response. Thalidomide was well tolerated, with constipation and
sedation being the major toxicities.
One patient developed a grade 2 peripheral neuropathy after treatment with
thalidomide for nearly a year.
There were two objective radiographic partial responses (6%), two minor
responses (6%), and 12 patients with stable disease (33%).
Eight patients were alive more than 1 year after starting thalidomide, although
almost all with tumor progression.
Changes in serum levels of basic fibroblastic growth factor (bFGF) were
correlated with time to tumor progression and overall survival.
Conclusion.
Thalidomide is a generally well-tolerated drug that may have antitumor activity
in a minority of patients with recurrent high-grade gliomas.
Future studies will better define the usefulness of thalidomide in newly
diagnosed patients with malignant gliomas and in combination with radiotherapy
and chemotherapy.
Additionally, studies will be needed to confirm the potential utility of changes
in serum bFGF as a marker of antiangiogenic activity and/or glioma growth.
PMID:
10673511 [PubMed - indexed for MEDLINE]
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