NICE verdict on Temozolomide: where next?

Temozolomide is a UK product developed in a CRC laboratory at Aston University by Malcolm Stevens and his team. It came to clinical testing in the early 1990s and the first UK study suggested activity in recurrent malignant glioma beyond that perceived for conventional therapy ( O'Reilly et al, 1993 ). This raised hope in a largely chemoresistant tumour with poor prognosis. However, the subsequent UK experience in a CRC multicentre phase II study in recurrent malignant glioma did not reproduce the results expected from the initial experience ( Bower et al, 1997 ). Time moved on and Temozolomide was licenced to Schering Plough. Following three preregistration studies which were the largest ever performed in patients with recurrent malignant glioma ( Yung et al, 1999 , 2000 ; Brada et al, 2001 ) it became available in clinical practice. The median progression free survival and survival were 5.4 and 13.6 months in anaplastic astrocytoma and 3 and 7.3 months in glioblastoma with 35% response rate in anaplastic astrocytoma and 6–8% in glioblastoma multiforme and quality of life benefit. Two studies had no comparative group and one randomized Phase II study demonstrated small progression free survival gain compared to single agent Procarbazine with no survival benefit ( Yung et al, 2000 ).