title: Long-term survival of patients with glioblastoma treated with radiotherapy and lomustine plus temozolomide.
abstract: OBJECTIVE
  To evaluate long-term survival in a prospective series of patients newly diagnosed with glioblastoma and treated with a combination of lomustine (CCNU), temozolomide (TMZ), and radiotherapy.
  
  
  METHODS
  Thirty-nine patients received radiotherapy of the tumor site only (60 Gy) and CCNU/TMZ chemotherapy (n = 31 received standard-dose CCNU, 100 mg/m2 on day 1 and TMZ 100 mg/m(2)/d on days 2 to 6; n = 8 received intensified-dose CCNU 110 mg/m(2) on day 1 and TMZ 150 mg/m(2) on days 2 to 6) for up to six courses.
  
  
  RESULTS
  In the whole cohort, the median overall survival (mOS) was 23.1 months; 47.4% survived for 2 years, and 18.5% survived for 4 years. After a median follow-up of 41.5 months, mOS had not been reached in the intensified group and was significantly higher than in the standard group (22.6 months; P = .024). In the intensified group, four of eight patients survived for at least 56 months, two of them without recurrence. O(6)-methylguanine-DNA methyltransferase (MGMT) gene promotor methylation in the tumor tissue was associated with significantly longer mOS (methylated, 34.3 months v nonmethylated, 12.5 months). A multivariate Cox proportional hazard model revealed MGMT status (methylated v nonmethylated; relative risk [RR] of death, 0.43; P = .003) and chemotherapy dose (intensified v standard; RR, 0.37; P = .012) as independent prognostic factors. WHO grade 4 hematoxicity was observed more frequently in the intensified group (57% v 16%).
  
  
  CONCLUSIONS
  The combination of radiotherapy, CCNU, and TMZ yielded promising long-term survival data in patients with newly diagnosed glioblastoma. Intensification of CCNU/TMZ chemotherapy may add an additional survival benefit, albeit with greater acute toxicity.
authors.affiliation: Division of Clinical Neurooncology, Department of Neurology, University of Bonn, Sigmund-Freud-Str 25, D-53105 Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Glas
authors.forename: Caroline
authors.initials: C
authors.lastname: Happold
authors.forename: Johannes
authors.initials: J
authors.lastname: Rieger
authors.forename: Dorothee
authors.initials: D
authors.lastname: Wiewrodt
authors.forename: Oliver
authors.initials: O
authors.lastname: Bähr
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Steinbach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wick
authors.forename: Rolf-Dieter
authors.initials: RD
authors.lastname: Kortmann
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Herrlinger
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005909:Glioblastoma / Q000401:mortality / Q000628:therapy*; D006801:Humans; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D000077204:Temozolomide
chemical_list: D008130:Lomustine; D003606:Dacarbazine; D000077204:Temozolomide