Résumé : Introduction: Despite the combined adjuvant treatment of radiotherapy plus chemotherapy with temozolomide (TMZ) followed by 6 cycles of temozolomide after surgery, the prognosis of patients with glioblastoma remains poor. We conducted a monocentric prospective study to explore the tolerance and potential efficacy of an early temozolomide cycle after surgery. Method: Patients with newly diagnosed glioblastoma (unmutated IDH1) and of poor prognosis (age > 50 years, biopsy or partial resection or unmethylated MGMT promoter) were prospectively included from June 2014 to 2017. They all received a cycle of 5 days of temozolomide between surgery and the combined adjuvant treatment. Results: Twelve patients of median age 64.5 years (45–73) were included in the study. The median doses of temozolomide administered were respectively 265 mg (225–300) for the early cycle; 130 mg (110–150) for the concomitant treatment and 310 mg (225–400) for the adjuvant one. Side effects during treatment were grade III lymphopenia, grade III neutropenia, fatigue and nausea/vomiting respectively in 4, 1, 7 and 5 patients. Progression-free survival and overall survival were respectively 90% and 91.7% at 6 months; 58.3 and 71.3% at 12 months; 31.1 and 71.3% at 18 months. Conclusion: Early postsurgical temozolomide treatment prior to standard adjuvant therapy for poor prognosis glioblastoma patients in our small prospective series presents toxicity and survival similar to those published in the literature for the general population of glioblastoma. These encouraging results should be confirmed by a multicentric study comparing this regiment with the standard treatment.