title: Survival of patients with newly diagnosed glioblastoma treated with radiation and temozolomide in research studies in the United States.
abstract: OBJECTIVE
  Novel agents are currently combined with radiation and temozolomide (RT + TMZ) in newly diagnosed glioblastoma using overall survival as the primary end point. Results of these phase II studies are typically compared with the phase III European Organization for Research and Treatment of Cancer (EORTC) survival data that resulted in RT + TMZ becoming standard therapy.
  
  
  METHODS
  The New Approaches to Brain Tumor Therapy (NABTT) Consortium assigned 365 patients with glioblastoma to four single-cohort studies with similar eligibility criteria. Patients received RT + TMZ with talampanel (n = 72), poly-ICLC (n = 97), or cilengitide (n = 112) or RT + TMZ alone with monitoring of CD4 counts (n = 84). Overall survival of those ages 18 to 70 years with glioblastoma was compared with published EORTC data.
  
  
  RESULTS
  NABTT and EORTC patients had comparable performance status and debulking surgery. Median, 12-month, and 24-month survival rates for the EORTC patients (n = 287) and the comparable NABTT patients receiving RT + TMZ and novel agents (n = 244) are 14.6 versus 19.6 months, 61% versus 81%, and 27% versus 37%, respectively. This represents a 37% reduction in odds of death (P < 0.0001) through 2 years of follow-up. NABTT and EORTC patients receiving only RT + TMZ had similar survival.
  
  
  CONCLUSIONS
  Newly diagnosed glioblastoma treated recently with RT + TMZ and talampanel, poly-ICLC, or cilengitide had significantly longer survival than similar patients treated with only RT + TMZ accrued internationally from 2000 to 2002. These differences could result from the novel agents or changing patterns of care. Until the reasons for these different survival rates are clarified, comparisons of outcomes from phase II studies with published RT + TMZ survival data should be interpreted with caution.
authors.affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, Maryland, USA. grossman@jhmi.edu.
authors.forename: Stuart A
authors.initials: SA
authors.lastname: Grossman
authors.forename: Xiaobu
authors.initials: X
authors.lastname: Ye
authors.forename: Steven
authors.initials: S
authors.lastname: Piantadosi
authors.forename: Serena
authors.initials: S
authors.lastname: Desideri
authors.forename: Louis B
authors.initials: LB
authors.lastname: Nabors
authors.forename: Myrna
authors.initials: M
authors.lastname: Rosenfeld
authors.forename: Joy
authors.initials: J
authors.lastname: Fisher
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D035843:Biomedical Research; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy / Q000628:therapy*; D002266:Carboxymethylcellulose Sodium / Q000031:analogs & derivatives / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D003131:Combined Modality Therapy; D016371:Cranial Irradiation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D007369:Interferon Inducers / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011070:Poly I-C / Q000627:therapeutic use; D011107:Polylysine / Q000031:analogs & derivatives / Q000627:therapeutic use; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D012910:Snake Venoms / Q000627:therapeutic use; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007369:Interferon Inducers; D018091:Receptors, AMPA; D012910:Snake Venoms; D001569:Benzodiazepines; D011107:Polylysine; C422910:Cilengitide; D003606:Dacarbazine; C019531:poly ICLC; C085266:talampanel; D002266:Carboxymethylcellulose Sodium; D011070:Poly I-C; D000077204:Temozolomide