title: NOA-05 phase 2 trial of procarbazine and lomustine therapy in gliomatosis cerebri.
abstract: OBJECTIVE
  The NOA-05 multicenter trial was performed to analyze the efficacy of primary chemotherapy with procarbazine and lomustine (PC) in patients with gliomatosis cerebri (GC) and to define clinical, imaging, and molecular factors influencing outcome.
  
  
  METHODS
  Thirty-five patients with previously untreated GC were treated with up to six 56-day courses of 110mg/m(2) lomustine on day 1 and 60mg/m(2) procarbazine on days 8 to 21. The primary endpoint was the rate of patients without therapy failure (defined as progressive disease, death from any cause, or termination of PC therapy before the end of course 4) at 8 months after the beginning of PC chemotherapy.
  
  
  RESULTS
  The failure-free survival rate at 8 months was 50.3%. Median progression-free survival was 14 months. At progression, 12 patients received salvage radiotherapy. Median overall survival was 30 months. Multivariate analysis revealed isocitrate dehydrogenase 1 (IDH1) gene mutation (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.02-0.58) and initial presentation without a bilateral symmetrical infiltration pattern on magnetic resonance imaging (HR 0.07, 95%CI 0.01-0.54) as independent prognostic factors associated with prolonged survival. IDH1 mutation was significantly associated with MGMT promoter methylation and an oligodendroglial tumor component.
  
  
  CONCLUSIONS
  PC chemotherapy is effective in GC. With the NOA-05 trial being the first prospective multicenter trial in GC, PC chemotherapy can be regarded as a promising option for the primary therapy of these tumors.
authors.affiliation: Division of Clinical Neuro-oncology, Department of Neurology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Glas
authors.forename: Oliver
authors.initials: O
authors.lastname: Bähr
authors.forename: Jörg
authors.initials: J
authors.lastname: Felsberg
authors.forename: Katja
authors.initials: K
authors.lastname: Rasch
authors.forename: Dorothee
authors.initials: D
authors.lastname: Wiewrodt
authors.forename: Martin
authors.initials: M
authors.lastname: Schabet
authors.forename: Matthias
authors.initials: M
authors.lastname: Simon
authors.forename: Horst
authors.initials: H
authors.lastname: Urbach
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Steinbach
authors.forename: Johannes
authors.initials: J
authors.lastname: Rieger
authors.forename: Rolf
authors.initials: R
authors.lastname: Fimmers
authors.forename: Michael
authors.initials: M
authors.lastname: Bamberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Nägele
authors.forename: Guido
authors.initials: G
authors.lastname: Reifenberger
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Herrlinger
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis; D001921:Brain / Q000473:pathology; D003131:Combined Modality Therapy; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D023381:Endpoint Determination; D005260:Female; D006801:Humans; D017567:Karnofsky Performance Status; D008130:Lomustine / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D018302:Neoplasms, Neuroepithelial / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011344:Procarbazine / Q000008:administration & dosage; D011379:Prognosis; D011446:Prospective Studies; D018401:Sample Size; D016019:Survival Analysis; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D011344:Procarbazine; D008130:Lomustine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes