title: Temozolomide added to whole brain radiotherapy in patients with multiple brain metastases of non-small-cell lung cancer: a multicentric Austrian phase II study.
abstract: BACKGROUND
  This multicentric randomized phase II study investigated the feasibility and toxicity of temozolomide (TMZ) added to whole brain radiotherapy (WBRT) followed by adjuvant TMZ in patients with multiple brain metastases of non-small-cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with multiple brain metastases from NSCLC aged ≥ 18 years, classified according to recursive partitioning analysis class I or II and with adequate organ functions were eligible. Treatment consisted of WBRT + TMZ 75 mg/m² for 2 weeks followed at day 28 by TMZ 100 mg/m²/day 2 weeks on/2 weeks off for up to 6 months (radiochemotherapy, RCT) or WBRT alone (radiotherapy, RT).
  
  
  RESULTS
  The study enrolled only 35 patients (22 patients in RCT and 13 in RT) and had to be closed prematurely due to poor accrual. The toxicity was mainly due to TMZ with WHO grade 3 and 4 thrombocytopenia in 3/22 versus 0/13, leucocytopenia in 1/22 versus 0/13 and lymphocytopenia in 7/22 versus 12/13 patients in RCT and RT respectively. Thirteen patients in RCT and six in RT progressed systemically and dropped out before first restaging of the response in brain. Median time to progression (TTP) was 2.4 months (95 % CI: 2-2.6 months) and 2.0 months (95 % CI: 0.5-3.5 months), median overall survival (OAS) was 3 months (95% CI: 1.7-3.1 months) and 6.3.months (95 % CI: 0.2-7.6 months) in RCT and RT, respectively.
  
  
  CONCLUSIONS
  Like other studies before on patients with brain metastases, insufficient number of recruited patients does not allow conclusions on efficacy and toxicity as the study closed prematurely.
authors.affiliation: Department of Internal Medicine I, Clinical Division of Oncology, Medical University of Vienna, Austria.
authors.forename: Marco Ronald
authors.initials: MR
authors.lastname: Hassler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pfeifer
authors.forename: Thomas Hendrik
authors.initials: TH
authors.lastname: Knocke-Abulesz
authors.forename: Klaus
authors.initials: K
authors.lastname: Geissler
authors.forename: Gabriele
authors.initials: G
authors.lastname: Altorjai
authors.forename: Karin
authors.initials: K
authors.lastname: Dieckmann
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use; D001317:Austria; D001932:Brain Neoplasms / Q000556:secondary* / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000556:secondary* / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D011832:Radiation Injuries / Q000209:etiology / Q000517:prevention & control; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide
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