Prolonged temozolomide for treatment of glioblastoma: preliminary clinical results and prognostic value of p53 overexpression

Abstract

We report retrospective data on the feasibility and efficacy of prolonging adjuvant temozolomide (TMZ) more than 6 months after chemoradiotherapy completion in patients with glioblastoma (GBM). Molecular prognostic factors were assessed. Data from 46 patients were reviewed. Patients received postoperative irradiation, 60 Gy in 30 fractions, combined with concurrent TMZ, 75 mg/m(2). Four weeks later, adjuvant TMZ was prescribed, 150-200 mg/m(2) for a total of 24 cycles unless there was progression or toxicity. Tumor samples were tested for the following prognostic factors: EGFR overexpression, 1p19q deletion, p53 overexpression and proliferation index. Overall survival (OS) was 84.8% at 6 months, 54.3% at 12 months, 26.1% at 18 months, and 21.7% at 24 months. Progression-free survival (PFS) was 73.9% at 6 months, 34.8% at 12 months, 15.2% at 18 months and 10.4% at 24 months. In the adjuvant phase, no treatment disruption for toxicity was necessary but eight patients required dose adaptation because of side effects. No significant molecular prognostic factor was evidenced for OS. We found that p53 overexpression was the only significant prognostic factor for PFS, with a median PFS of 9.3 months versus 7 months for patients without p53 overexpression (P = 0.031). This study suggests that delivering adjuvant TMZ therapy for more than 6 months is feasible in patients with GBM. Efficacy data warrant further prospective assessment with the focus on molecular prognostic factors, such as p53 overexpression, which was found to be the only significant molecular prognostic factor for outcome.