title: Short-term radiotherapy followed by adjuvant chemotherapy in poor-prognosis patients with glioblastoma.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Forty-five patients with a newly diagnosed glioblastoma, older than 70 years or aged 50-70 years and with a Karnofsky performance score <or=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/m(2) 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.
authors.affiliation: Department of Radiotherapy, S. Andrea Hospital, University Sapienza, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Muni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Minniti
authors.forename: Gaetano
authors.initials: G
authors.lastname: Lanzetta
authors.forename: Paola
authors.initials: P
authors.lastname: Caporello
authors.forename: Alessandro
authors.initials: A
authors.lastname: Frati
authors.forename: Maurizio Maurizi
authors.initials: MM
authors.lastname: Enrici
authors.forename: Paolo
authors.initials: P
authors.lastname: Marchetti
authors.forename: Riccardo Maurizi
authors.initials: RM
authors.lastname: Enrici
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide