title: Phase II trial of temozolomide in patients with progressive low-grade glioma.
abstract: OBJECTIVE
  Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma.
  
  
  METHODS
  Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m(2)/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity.
  
  
  RESULTS
  Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to infinity months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced > or = grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death.
  
  
  CONCLUSIONS
  Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. quinn008@mc.duke.edu
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Quinn
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: John H
authors.initials: JH
authors.lastname: Sampson
authors.forename: James M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Sridharan
authors.initials: S
authors.lastname: Gururangan
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Nicholas
authors.initials: N
authors.lastname: Avgeropoulos
authors.forename: Jonathan
authors.initials: J
authors.lastname: Finlay
authors.forename: Sandra
authors.initials: S
authors.lastname: Tourt-Uhlig
authors.forename: Mary Lou
authors.initials: ML
authors.lastname: Affronti
authors.forename: Brandon
authors.initials: B
authors.lastname: Evans
authors.forename: Valerie
authors.initials: V
authors.lastname: Stafford-Fox
authors.forename: Sara
authors.initials: S
authors.lastname: Zaknoen
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
mesh_terms: D000293:Adolescent; D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects / Q000627:therapeutic use*; D002648:Child; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide