title: Randomized, double-blind, placebo-controlled trial of marimastat in glioblastoma multiforme patients following surgery and irradiation.
abstract: OBJECTIVE
  Because raised matrix metalloprotease (MMP) levels are associated with glioma invasion and angiogenesis, we tested the efficacy of marimastat (MT) an orally active drug that can reduce MMP levels, in patients with gliomas.
  
  
  METHODS
  A total of 162 patients with intracranial glioblastoma multiforme or gliosarcomas who had undergone surgery and radiotherapy participated in this multicenter, double-blind, placebo-controlled, parallel group study conducted at 20 institutions. Seventy-nine patients (57 male, 22 female, median age 58 years) were randomized to receive placebo (PB), and 83 patients (51 male, 32 female, median age 57 years) were randomized to receive MT, 10 mg orally twice daily, until tumor progression.
  
  
  RESULTS
  This intention-to-treat efficacy analysis showed no statistically significant difference between MT and PB groups with respect to survival (P = 0.38, log rank test). The median survival time from protocol initiation was 37.9 weeks for the PB group and 42.9 weeks for the MT group, with a hazard ratio of 1.16 (95% CI 0.83 to 1.60). There were no statistically significant differences in quality of life between the PB and MT groups, as assessed by the FACT-BR questionnaire. Musculoskeletal toxicities led to dose modification or withdrawal in 20% of MT-treated and 1.2% of PB-treated patients.
  
  
  CONCLUSIONS
  MT does not improve survival in patients with glioblastoma or gliosarcoma following surgery and radiotherapy. Therefore, single-agent MT appears unwarranted; however, MT in combination with cytotoxic chemotherapy may be warranted, as suggested by observations in our study and other studies.
authors.affiliation: Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA. vlevin@mdanderson.org
authors.forename: Victor A
authors.initials: VA
authors.lastname: Levin
authors.forename: Surasak
authors.initials: S
authors.lastname: Phuphanich
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Peter A
authors.initials: PA
authors.lastname: Forsyth
authors.forename: Rolando Del
authors.initials: RD
authors.lastname: Maestro
authors.forename: James R
authors.initials: JR
authors.lastname: Perry
authors.forename: Gregory N
authors.initials: GN
authors.lastname: Fuller
authors.forename: Mark
authors.initials: M
authors.lastname: Baillet
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000201:enzymology; D018316:Gliosarcoma / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D006877:Hydroxamic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000139:chemically induced; D011788:Quality of Life; D016019:Survival Analysis; D017211:Treatment Failure
chemical_list: D004791:Enzyme Inhibitors; D006877:Hydroxamic Acids; D061965:Matrix Metalloproteinase Inhibitors; C100342:marimastat; D020782:Matrix Metalloproteinases