Surgery, radiotherapy and temozolomide in treating high-grade gliomas

Abstract

Temozolomide (TMZ) a recent, oral, second generation alkylating agent is a chemotherapeutic with demonstrated efficacy for the treatment of high-grade gliomas. The efficacy of TMZ has been demonstrated in both pre-clinical and phase I and II studies. The goal of this study is to determine the activity and safety of temozolomide in improving overall survival (OS), progression-free survival (PFS) and health-related quality of life (HQL) in patient with malignant gliomas treated by surgery, radiotherapy and temozolomide. Twelve patients with newly diagnosed glioblastoma (GBM), and anaplastic astrocytoma (AA) were studied. The mean follow-up period was 12 months. The overall response rate for all histological groups was 33% (4 patients), 6 patients (50%) showed a stabilization of disease. The median progression-free survival (PFS) and overall survival (OS) was respectively 8.35 and 14.1 months; time to progression was 36 week ranging from 20 to 46 In all patients, treatment with temozolomide was associated with improvement of performance status including the patient showing disease progression; Karnofski score improved in all patients by a minimum of 10, with a median of 20 at 6 months. No patient stopped the treatment due to side-effects, no major adverse events were recorded. In two cases of glioblastoma, we observed complete response and after three years, the quality of life is optimal. Surgery allows to establish a histopathological diagnosis, to improve signs and symptoms which are attributable to intracranial hypertension or tumour topography, and to reduce the number of target cells for adjunctive therapies. Radiotherapy improves survival and TMZ chemotherapy that is given after radiotherapy adds survival benefit for patients. Because of its favourable pharmacokinetic and pharmacodynamic properties and improved tolerability. Temozolomide appears to be an ideal, first-line, single-agent, with a safe profile and demonstrated HQL benefits in patients with high-grade gliomas.