title: Survival and neurologic outcomes in a randomized trial of motexafin gadolinium and whole-brain radiation therapy in brain metastases.
abstract: OBJECTIVE
  This phase III randomized trial evaluated survival as well as neurologic and neurocognitive function in patients with brain metastases from solid tumors receiving whole-brain radiation therapy (WBRT) with or without motexafin gadolinium (MGd).
  
  
  METHODS
  Patients were randomly assigned to 30 Gy of WBRT +/- 5 mg/kg/d MGd. Survival and time to neurologic progression determined by a blinded events review committee (ERC) were coprimary end points. Standardized investigator neurologic assessment and neurocognitive testing were evaluated.
  
  
  RESULTS
  Four hundred one (251 non-small-cell lung cancer) patients were enrolled. There was no significant difference by treatment arm in survival (median, 5.2 months for MGd v 4.9 months for WBRT; P =.48) or time to neurologic progression (median, 9.5 months for MGd v 8.3 months for WBRT; P =.95). Treatment with MGd improved time to neurologic progression in patients with lung cancer (median, not reached for MGd v 7.4 months for WBRT; P =.048, unadjusted). By investigator, MGd improved time to neurologic progression in all patients (median, 4.3 months for MGd v 3.8 months for WBRT; P =.018) and in lung cancer patients (median, 5.5 months for MGd v 3.7 months for WBRT; P =.025). MGd improved neurocognitive function in lung cancer patients.
  
  
  CONCLUSIONS
  The overall results did not demonstrate significant differences by treatment arm for survival and ERC time to neurologic progression. Investigator neurologic assessments demonstrated an MGd treatment benefit in all patients. In lung cancer patients, ERC- and investigator-determined time to neurologic progression demonstrated an MGd treatment benefit. MGd may improve time to neurologic and neurocognitive progression in lung cancer.
authors.affiliation: University of Wisconsin-Madison, Department Human Oncology Radiation Oncology, 53792, USA. mehta@mail.humonc.wisc.edu
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.forename: Patrick
authors.initials: P
authors.lastname: Rodrigus
authors.forename: C H J
authors.initials: CH
authors.lastname: Terhaard
authors.forename: Aroor
authors.initials: A
authors.lastname: Rao
authors.forename: John
authors.initials: J
authors.lastname: Suh
authors.forename: Wilson
authors.initials: W
authors.lastname: Roa
authors.forename: Luis
authors.initials: L
authors.lastname: Souhami
authors.forename: Andrea
authors.initials: A
authors.lastname: Bezjak
authors.forename: Mark
authors.initials: M
authors.lastname: Leibenhaut
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: Christopher
authors.initials: C
authors.lastname: Schultz
authors.forename: Robert
authors.initials: R
authors.lastname: Timmerman
authors.forename: Walter
authors.initials: W
authors.lastname: Curran
authors.forename: Jennifer
authors.initials: J
authors.lastname: Smith
authors.forename: See-Chun
authors.initials: SC
authors.lastname: Phan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Miller
authors.forename: Markus F
authors.initials: MF
authors.lastname: Renschler
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000556:secondary*; D003071:Cognition; D003131:Combined Modality Therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D013534:Survival; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D008665:Metalloporphyrins; C437683:motexafin gadolinium