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Thalidomide
as an anti-angiogenic agent in relapsed gliomas
Short SC, Traish D, Dowe A, Hines F, Gore M, Brada M.
Unit of Neuro-Oncology, The Institute of Cancer Research and The
Royal Marsden NHS Trust, Sutton, Surrey, UK. susan.short@rmh.nthames.nhs.uk
Background. Thalidomide (alpha-phthalimidoglutarimide), a synthetic
sedative drug, has anti-angiogenic properties due to inhibition of growth-factor
mediated neovascularisation and has been shown to inhibit tumour growth in
experimental solid tumour models.
Aim.
To assess response of recurrent malignant gliomas to thalidomide.
Methods.
Eighteen patients with recurrent gliomas were enrolled to an open,
non-randomised phase II trial between October 1997 and December 1999.
All patients had failed following treatment with radiotherapy and chemotherapy
with PCV and/or temozolomide regimens.
Eleven patients had high-grade gliomas de novo and 7 high-grade gliomas
following transformation of low-grade gliomas.
Thalidomide was prescribed at 100 mg/day p.o. continuously.
Response was assessed at 4-weekly intervals.
Disease progression was defined as neurological deterioration and/or
radiological evidence of increased tumour size.
Treatment was discontinued at the time of disease progression, or if toxicity
occurred, or at patients' request.
Results.
Thalidomide was prescribed for a median of 42 days (range 7-244).
Treatment was discontinued due to toxicity (peripheral sensory neuropathy) in 1
patient.
Six patients died before response could be fully assessed and are classified as
non-responders.
Of 12 who continued treatment for more than 4 weeks, 1 patient had clinical and
radiological response (PR), 2 patients had stable disease for 2 and 4 months
respectively and 9 patients had disease progression.
The median survival from the start of thalidomide was 2.5 months.
Conclusion.
The efficacy of thalidomide in terms of response in recurrent gliomas is low,
with a partial response rate of only 6%.
Future studies should investigate thalidomide in combination with other agents
and at an earlier stage of disease.
Methods to assess anti-angiogenic properties such as changes in tumour
vasculature could be employed as initial surrogate end-points in the
investigation of efficacy.
PMID: 11349879 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11349879
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