title: Whole-brain radiation therapy plus concomitant temozolomide for the treatment of brain metastases from non-small-cell lung cancer: a randomized, open-label phase II study.
abstract: BACKGROUND
  A previously published study of temozolomide concurrent with whole-brain radiation therapy (WBRT) reported significant improvement in response rates and a nonsignificant trend toward improved overall survival compared with WBRT alone in patients with brain metastases primarily from lung cancer. This study sought to confirm the benefit of adding temozolomide to WBRT in patients with non-small-cell lung cancer (NSCLC) with brain metastases.
  
  
  METHODS
  This planned phase III study (target = 380 events) was converted to a phase II study (target = 70 events) because of poor enrollment. Patients with NSCLC and > or = 1 newly diagnosed brain lesion were randomized to WBRT (30 Gy in 10 fractions) alone or combined with temozolomide (75 mg/m2/day) for 21 or 28 days. Endpoints included overall survival and time to central nervous system (CNS) progression.
  
  
  RESULTS
  Median overall survival and median time to CNS progression was 4.4 and 3.1 months in the WBRT + temozolomide arm (n = 47) versus 5.7 and 3.8 months in the WBRT arm (n = 48). However, there were imbalances in the percentages of patients receiving previous chemotherapy and with synchronous brain metastases. Adding temozolomide to WBRT increased the frequency of nausea, vomiting, alopecia, fatigue, anorexia, and constipation. Most adverse events were mild to moderate.
  
  
  CONCLUSIONS
  The benefit of adding temozolomide to WBRT was not confirmed; however, the accrual goal for the planned phase III trial was not reached, and the study regimen differed from regimens used previously. Therefore, the role of temozolomide in treating brain metastases remains unresolved.
authors.affiliation: Department of Clinical Oncology, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. danielchua@hksh.com
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Maciej
authors.initials: M
authors.lastname: Krzakowski
authors.forename: Christos
authors.initials: C
authors.lastname: Chouaid
authors.forename: Maria G
authors.initials: MG
authors.lastname: Pallotta
authors.forename: Jose I
authors.initials: JI
authors.lastname: Martinez
authors.forename: Maya
authors.initials: M
authors.lastname: Gottfried
authors.forename: Walter
authors.initials: W
authors.lastname: Curran
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Throuvalas
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000009:adverse effects; D001932:Brain Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D003131:Combined Modality Therapy; D016371:Cranial Irradiation / Q000009:adverse effects / Q000379:methods; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide