A Phase II Trial of Primary Chemotherapy with Temozolomide in Patients with Low-Grade Cerebral Gliomas.
Louis Viviers, Michael Brada, Frances Hines, Juliet Britton, Charlotte Abson, Susan Ashley, Royal Marsden Hosp, London, UK.
Presented at the American Society Of Clinical Oncology, 2000 Conference

We assessed the efficacy of Temozolomide in a prospective Phase II study of patients with stable and progressive low-grade glioma who had no previous antitumour therapy other than surgery. Patients received Temozolomide (200 mg/m2/day) on a 28-day cycle for a maximum of 12 cycles or until the time of tumour progression. Objective response assessment consisted of 3-monthly MRI and monthly clinical evaluation and health-related quality of life (HQL) scores using a validated instrument (QLQC30 & BCM). 25 patients (12 men, 13 females; mean age of 39 years) with WHO grade II astrocytoma (18) and oligodendroglioma (7) were enrolled since March 1998. Median follow up is 9 months (range 1-20 months). 18 patients had biopsy alone and 7 incomplete resection; all had measurable disease on MRI seen as high signal intensity region on T2W and FLAIR sequences. 5 patients completed 6 and 7 patients 12 months of treatment. 9 of 10 symptomatic patients (recurrent seizures were main symptom) had clinical benefit with improvement in symptoms and HQL scores. Objective radiological response demonstrated slow reduction in the size of the abnormal signal intensity area of 21% (range 25-47%) at 6 months and 37% (range 0 - 75%) at 12 months determined by the product of 2 largest perpendicular diameters. Of 12 patients who received a minimum of 6 cycles of chemotherapy 3/12 had PR, 5/12 MR and 3/12 SD. 2/23 patients had PD and one patient died of unrelated causes (presumed PE). One patient had grade 3/4 haematological toxicity. Preliminary results of this ongoing trial suggest that Temozolomide has single agent activity in the treatment of patients with low grade cerebral glioma.