Thalidomide as an anti-angiogenic agent in relapsed gliomas

Background. Thalidomide (alpha -phthalimidoglutarimide), a synthetic sedati ve 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 gliom as de novo and 7 high-grade gliomas following transformation of low-grade g liomas. Thalidomide was prescribed at 100 mg/day p.o. continuously. Respons e was assessed at 4-weekly intervals. Disease progression was defined as ne urological deterioration and/or radiological evidence of increased tumour s ize. Treatment was discontinued at the time of disease progression, or if t oxicity 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 t han 4 weeks, 1 patient had clinical and radiological response (PR), 2 patie nts had stable disease for 2 and 4 months respectively and 9 patients had d isease progression. The median survival from the start of thalidomide was 2 .5 months. Conclusion. The efficacy of thalidomide in terms of response in recurrent g liomas is low, with a partial response rate of only 6%. Future studies shou ld investigate thalidomide in combination with other agents and at an earli er stage of disease. Methods to assess anti-angiogenic properties such as c hanges in tumour vasculature could be employed as initial surrogate end-poi nts in the investigation of efficacy.