title: Strategies to prevent brain metastasis in high-risk non-small-cell lung cancer: lessons learned from a randomized study of maintenance temozolomide versus observation.
abstract: BACKGROUND
  This study investigated whether maintenance temozolomide (TMZ) after definitive therapy for locally advanced non-small-cell lung cancer (NSCLC) could decrease the incidence of brain metastasis (BM).
  
  
  METHODS
  Eligible patients included those with stage IIIA, IIIB, or IV (for stage IV, only with malignant pleural/pericardial effusion) NSCLC with no BM at diagnosis and stable disease, partial response, or complete response after first-line chemotherapy using at least 2 agents. Patients were randomized to observation or TMZ (75 mg/m(2) for 21 consecutive days followed by a 7-day rest for up to 6 cycles or progression). The primary end point was incidence of radiographically diagnosed BM within 12 months from day 1 of first-line chemotherapy. Secondary end points included overall survival (OS), time to progression, incidence of BM at first progression, and toxicity.
  
  
  RESULTS
  The study was closed early on the basis of a futility analysis; 45 of 53 enrolled patients were evaluable from an original target of 100. No difference was noted in the incidence of BM at 1 year in the TMZ and observation groups (18% and 13%, respectively), in median time to progression (11.7 and 10.7 months, respectively), or in median OS (27.1 and 22.5 months, respectively). Common Terminology Criteria for Adverse Events grade 3 or 4 adverse events were 46% in the TMZ group and 19% in the observation group.
  
  
  CONCLUSIONS
  TMZ monotherapy does not appear to decrease the incidence of BM in patients with locally advanced NSCLC. These results considered in the context of the existing literature have implications for future clinical trial design.
authors: Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD.
authors: D Hunter
authors: DH
authors: Boggs
authors: Departments of Medicine, Human Oncology, and Neurology, University of Wisconsin, Madison, WI.
authors: H Ian
authors: HI
authors: Robins
authors: Hematology and Oncology, University of Pennsylvania, Philadelphia, PA.
authors: Corey J
authors: CJ
authors: Langer
authors: Department of Medical Oncology, University of Wisconsin, Madison, WI.
authors: Anne M
authors: AM
authors: Traynor
authors: Department of Hematology and Oncology, Providence Saint Joseph Medical Center, Burbank, CA.
authors: Maurice J
authors: MJ
authors: Berkowitz
authors: Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD. Electronic address: mmehta@umm.edu.
authors: Minesh P
authors: MP
authors: Mehta
mesh_terms: D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D001932:Brain Neoplasms / Q000401:mortality* / Q000517:prevention & control* / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000517:prevention & control* / Q000556:secondary*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D057239:Early Termination of Clinical Trials; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011859:Radiography; D012306:Risk; D016019:Survival Analysis; D000077204:Temozolomide
chemical_list: D003606:Dacarbazine; D000077204:Temozolomide
keywords: Brain metastasis; Non–small-cell lung cancer; Prophylactic cranial irradiation; Prophylaxis; Temozolomide