A Phase II trial of Neo-adjuvant Temozolomide followed by Hypofractionated Accelerated Radiotherapy with Concurrent and Adjuvant Temozolomide for Patients with Glioblastoma
Mené sur 50 patients atteints d'un glioblastome (durée médiane de suivi : 22,3 mois), cet essai de phase II évalue la faisabilité et la toxicité d'un traitement par témozolomide suivi d'une radiothérapie hyperfractionnée accélérée en combinaison avec ce même anticancéreux
Background : We performed a phase II trial of neo-adjuvant Temozolomide (TMZ), followed by hypofractionated accelerated radiotherapy (HART) with concurrent TMZ, and adjuvant TMZ in patients with newly diagnosed Glioblastoma (GBM) to determine whether neo-adjuvant TMZ would safely improve outcomes in this group of patients prior to subsequent cytotoxic therapy. Methods : Newly diagnosed adult patients with GBM and KPS > 60 were eligible. Neo-adjuvant TMZ started 2 to 3 weeks from surgery at daily dose of 75 mg/m2 for 2 weeks prior to delivering HART (60 Gy in 20 daily fractions) with concurrent and adjuvant TMZ. The primary end-points were feasibility and toxicity. Secondary end-points included overall survival (OS) and progression-free survival (PFS). Results : Fifty patients were accrued. Median follow-up for patients at risk was 44.0 months, and 22.3 months for all 50 patients. Except for one patient who developed infection, and another one who progressed during HART, all patients completed protocol therapy as planned. The median OS and PFS were 22.3 months (95% CI, 14.6-42.7) and 13.7 months (95% CI, 8.0-33.3), respectively. The 4-year OS rates were 30.4% for the entire cohort, 53.3% and 14.0% for patients with Methylated (n=21) and Unmethylated (n=27) MGMT-gene promoter tumors, respectively. One patient experienced grade-5 pancytopenia during HART and another one had transient grade-4 hepatotoxicity. Thirteen patients underwent second surgery: 2 had intracranial infection, 3 recurrences, 4 recurrences and radiation-induced damage, and 4 radiation-induced damage only. Conclusion : This novel approach of neo-adjuvant TMZ is associated with an encouraging favorable long-term survival with acceptable toxicity. Future comparative trial of efficacy of this regimen is warranted.