Short-term Radiotherapy followed by Adjuvant Chemotherapy in Poor-Prognosis Patients with Glioblastoma

Abstract

Objectives The optimal treatment for patients with glioblastoma with unfavorable prognostic factors, such as old age and low performance status, remains controversial. We conducted a prospective study to assess the effect of temozolomide and short-course radiation versus short-course radiation alone in the treatment of poor-prognosis patients with newly diagnosed glioblastoma. Patients and methods Forty-five patients with a newly diagnosed glioblastoma, older than 70 years or aged 50–70 years and with a Karnofsky performance score ≤70 were enrolled in this prospective study. Twenty-three patients were treated with an abbreviated course of radiotherapy (30 Gy in 6 fractions over 2 weeks) and 22 patients with the same radiotherapy schedule plus adjuvant temozolomide at the dose of 150–200 mg/m2 for 5 days every 28-day cycle. The primary end point was overall survival. Secondary end points included progression-free survival and toxicity. Results Median overall survival was 7.3 months in the radiotherapy group and 9.4 months in the radiotherapy plus temozolomide group (P = 0.003), with respective 6-month overall survivals of 78% and 95%, respectively. Median progression-free survival was 4.4 months in the radiotherapy group and 5.5 months in the radiotherapy plus temozolomide group (P = 0.01), and respective 6-month progression-free survival rates were 22% and 45%. In multivariate analysis, Karnofsky performance score was the only significant independent predictive factor of survival (P = 0.03). Adverse effects of radiotherapy were mainly represented by neurotoxicity (24%), which resolved in most cases with the use of steroids. Grade 3-4 hematologic toxicity occurred in 36% of patients treated with temozolomide. Conclusions The addition of temozolomide to short-term radiotherapy resulted in a statistically significant survival benefit with minimal additional toxicity in poor-prognosis patients with newly diagnosed glioblastoma. Future studies need to define the best combined regimens of radiotherapy and temozolomide on survival and quality of life in this subgroup of patients.