Thalidomide as an anti-angiogenic agent in relapsed gliomas.

Abstract

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.

• Authors: S C Short, D Traish, A Dowe, F Hines, M Gore, M Brada
• Journal: Journal of neuro-oncology (J Neurooncol) Vol. 51 Issue 1 Pg. 41-5 (Jan 2001) ISSN: 0167-594X [Print] United States
• PMID: 11349879 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Thalidomide

Topics

• Adult
• Angiogenesis Inhibitors (therapeutic use)
• Brain Neoplasms (drug therapy, mortality)
• Disease Progression
• Glioma (drug therapy, mortality)
• Humans
• Middle Aged
• Neoplasm Recurrence, Local
• Survival Analysis
• Thalidomide (therapeutic use)
• Treatment Outcome