title: Phase II study of high central dose Gamma Knife radiosurgery and marimastat in patients with recurrent malignant glioma.
abstract: OBJECTIVE
  To assess the outcome of high central dose Gamma Knife radiosurgery plus marimastat in patients with recurrent malignant glioma.
  
  
  METHODS
  Twenty-six patients with recurrent malignant glioma were enrolled in a prospective Phase II study between November 1996 and January 1999. The radiosurgery dose was prescribed at the 25-30% isodose surface to increase the dose substantially within the tumor's presumably hypoxic core. Marimastat was administered after radiosurgery to restrict regional tumor progression. Survival was compared with that of historical patients treated at our institution with standard radiosurgery.
  
  
  RESULTS
  The median times to progression after radiosurgery for Grade 3 and 4 patients was 31 and 15 weeks, respectively. The corresponding median survival time after radiosurgery was 68 and 38 weeks. The median survival time after radiosurgery in the historical patients was 59 and 44 weeks.
  
  
  CONCLUSIONS
  The dual strategies of using high central dose radiosurgery to overcome tumor hypoxia together with marimastat to inhibit local tumor invasion may offer a small survival advantage for recurrent Grade 3 tumors; they do not offer an advantage for recurrent Grade 4 tumors.
authors.affiliation: Department of Radiation Oncology, University of California, San Francisco, School of Medicine, San Francisco, CA 94143-0226, USA. larson@radonc4.ucsf.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Larson
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Lamborn
authors.forename: Vernon
authors.initials: V
authors.lastname: Smith
authors.forename: Penny K
authors.initials: PK
authors.lastname: Sneed
authors.forename: Susan
authors.initials: S
authors.lastname: Chang
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Nicholas
authors.forename: William M
authors.initials: WM
authors.lastname: Wara
authors.forename: Daniel
authors.initials: D
authors.lastname: Devriendt
authors.forename: Sandeep
authors.initials: S
authors.lastname: Kunwar
authors.forename: Mitch
authors.initials: M
authors.lastname: Berger
authors.forename: Michael W
authors.initials: MW
authors.lastname: McDermott
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000401:mortality / Q000601:surgery*; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000401:mortality / Q000601:surgery*; D006801:Humans; D006877:Hydroxamic Acids / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016634:Radiosurgery / Q000379:methods*; D012008:Recurrence; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; C100342:marimastat