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Phase
II trial of thalidomide and carmustine for patients with recurrent high-grade
gliomas
Fine HA, Wen PY, Maher EA, Viscosi E, Batchelor T, Lakhani N, Figg WD, Purow
BW, Borkowf CB
Neuro-Oncology Branch, Center for Cancer Research, National
Cancer Institute, National Institutes of Health, 10 Center Drive, MSC 1911,
Building 10, Room 12S245, Bethesda, MD 20892-1911, USA.
hfine@mail.nih.gov.
Purpose. The use of thalidomide as an antiangiogenic agent has met with
only limited success in the treatment of malignant gliomas.
On the basis of preclinical data demonstrating synergistic antitumor activity
when antiangiogenic agents are combined with cytotoxic agents, we explored the
clinical activity of the combination of thalidomide and carmustine (BCNU) in
patients with recurrent high-grade gliomas.
Patients
and Methods. Patients with a histologic diagnosis of high-grade glioma and
radiographic evidence of tumor progression after standard surgery, radiation,
and chemotherapy were eligible for the study.
Patients received BCNU 200 mg/m2 on day 1 of every 6-week cycle, and 800 mg/d of
thalidomide that was escalated to a maximal dose of 1,200 mg/d as
tolerated.
Results.
A total of 40 patients (38 with glioblastomas, two with anaplastic gliomas) were
accrued to the study.
The combination of thalidomide and BCNU was well tolerated; mild
myelosuppression and mild to moderate sedation were the most common side
effects.
The median progression-free survival (100 days) and the objective radiographic
response rate (24%) for patients with glioblastoma compared favorably with data
from historical controls.
Conclusion.
This is one of the first clinical trials to evaluate the strategy of combining a
putative antiangiogenic agent with a cytotoxic agent in patients with primary
brain tumors.
Our data demonstrate that thalidomide in combination with BCNU is well tolerated
and has antitumor activity in patients with recurrent high-grade gliomas.
Although the combination seems to be more active than either agent alone, such
conclusions await confirmatory trials.
PMID:
12805330 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12805330&dopt=Abstract |
