title: Temozolomide combined with irradiation as postoperative treatment of primary glioblastoma multiforme. Phase I/II study.
abstract: OBJECTIVE
  The role of radiochemotherapy in the treatment of primary glioblastoma multiforme is still discussed controversially. To evaluate the feasibility and toxicity of irradiation and concomitant administration of 50 mg/m(2) temozolomide in patients with primary malignant glioma, this phase I/II study was conducted.
  
  
  METHODS
  53 Patients with histologically confirmed WHO grade IV malignant glioma were enrolled into the study. All patients were treated with radiation therapy up to a total dose of 60 Gy using conventional fractionation of 5 x 2.0 Gy/week. Temozolomide was administered orally each therapy day at a dose of 50 mg/m(2).
  
  
  RESULTS
  Prior to radiochemotherapy, complete resection (n = 14), subtotal resection (n = 22) or a biopsy (n = 17) of the tumor was performed. The median time interval between surgery and radiochemotherapy was 21 days. Treatment-related toxicity was very mild. Acute toxicity > grade 2 was observed in one patient who developed grade 4 hemotoxicity. Minor side effects of chemotherapy included nausea and vomiting. No severe late effects were observed. Median progression-free and overall survival were 8 and 19 months, respectively. The overall survival rate was 72% at 1 and 26% at 2 years. Age and extent of surgery significantly influenced survival.
  
  
  CONCLUSIONS
  The combination of temozolomide plus radiation therapy is feasible and safe in terms of toxicity. Overall survival times were relatively long compared to survival times reported for radiotherapy alone. The application of 50 mg/m(2) of temozolomide can be performed throughout the whole time course without interruption due to side effects and might largely contribute to the prolonged overall survival. Further evaluation is warranted as to which dose of temozolomide is optimal with regard to tumor response and toxicity.
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany. Stephanie.Combs@med.uni-heidelberg.de
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Combs
authors.forename: Sybille
authors.initials: S
authors.lastname: Gutwein
authors.forename: Daniela
authors.initials: D
authors.lastname: Schulz-Ertner
authors.forename: Michael
authors.initials: M
authors.lastname: van Kampen
authors.forename: Christoph
authors.initials: C
authors.lastname: Thilmann
authors.forename: Lutz
authors.initials: L
authors.lastname: Edler
authors.forename: Michael M
authors.initials: MM
authors.lastname: Wannenmacher
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use / Q000633:toxicity*; D001772:Blood Cell Count; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use / Q000633:toxicity; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D000077204:Temozolomide; D013997:Time Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide