title: Phase II trial of 7 days on/7 days off temozolmide for recurrent high-grade glioma.
abstract: BACKGROUND
  A phase II trial was performed to evaluate the efficacy of a dose-dense, 7 days on/7 days off schedule of temozolomide for patients with recurrent high-grade gliomas (HGG).
  
  
  METHODS
  Sixty patients with recurrent HGG received temozolomide at 150 mg/m(2)/day on days 1-7 and days 15-21 during each 4-week cycle. The primary endpoint was 6-month progression-free survival (PFS-6), with a secondary endpoint of overall survival (OS). A further exploratory objective included the investigation of whether methylation status of the O(6)-methylguanine-DNA methyltransferase (MGMT) promoter within tumor tissue predicted outcomes.
  
  
  RESULTS
  Among patients with glioblastoma (n = 40), PFS-6 was 10% (95% CI, 3%-24%) with median OS of 21.6 weeks (95% CI, 16.9-30.6 weeks). PFS-6 for grade III glioma patients (n = 20) was 50% (95% CI, 27%-73%), and median OS was 100.6 weeks (95% CI, 67 weeks to not reached). There were trends towards longer PFS and OS with MGMT promoter methylation (log-rank test; P = .06 for PFS; P = .07 for OS). Additionally, bevacizumab-naïve glioblastoma patients had significantly longer PFS and OS (median PFS was 8.07 weeks [95% CI, 8 weeks to not reached] vs 7.57 weeks [95% CI, 7.29-8.29 weeks], log-rank test, P < .001; median OS was 62 weeks [26.1 weeks to not reached] vs 18.2 weeks [13.9-27.3 weeks], log-rank test, P < .001).
  
  
  CONCLUSIONS
  The dose-dense temozolomide regimen was well tolerated, although it has no significant activity in this population. Clinical trials.gov identified. NCT00619112 (available at http://clinicaltrials.gov/ct2/show/NCT00619112).
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: Seunggu J
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: John D
authors.initials: JD
authors.lastname: Rolston
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Clarke
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: Michael D
authors.initials: MD
authors.lastname: Prados
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: Ashley
authors.initials: A
authors.lastname: DeSilva
authors.affiliation: Department of Neurological Surgery, University of California, San Francisco, California (S.J.H., J.D.R., A.M.M., J.L.C., M.D.P., S.M.C., M.S.B., A.D., N.A.B.); Department of Epidemiology and Biostatistics, University of California, San Francisco, California (A.M.M.).
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Butowski
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D019175:DNA Methylation; D015254:DNA Modification Methylases; D045643:DNA Repair Enzymes; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018906:Antineoplastic Agents, Alkylating; D025521:Tumor Suppressor Proteins; D000068258:Bevacizumab; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: bevacizumab; chemotherapy; glioblastoma; glioma; temozolomide