title: Multi-institutional phase II study of temozolomide administered twice daily in the treatment of recurrent high-grade gliomas.
abstract: BACKGROUND
  The prognosis for patients with recurrent high-grade gliomas is poor and treatment options are limited. Current chemotherapeutic regimens can improve clinical outcomes, but extend survival by only a few months. Temozolomide is a methylating agent that is typically administered once daily. Because preclinical studies suggested that a twice-daily dosing schedule might be more effective, the safety and efficacy of twice-daily dosing of temozolomide were studied in patients with recurrent gliomas at their first, second, or third recurrence.
  
  
  METHODS
  This multi-institutional trial enrolled 120 patients with recurrent glioblastoma multiforme (GBM), anaplastic astrocytoma (AA), or anaplastic oligodendroglioma (AO). An initial oral dose of 200 mg/m(2) of temozolomide was followed by 9 consecutive doses of 90-mg/m(2) every 12 hours. Treatment cycles were repeated every 28 days. Doses were escalated to 100 mg/m(2) twice daily in the absence of unacceptable toxicity or were reduced if unacceptable toxicity occurred.
  
  
  RESULTS
  For GBM, AA, and AO patients, respectively, the median progression-free survival (PFS) was 4.2 months, 5.8 months, and 7.7 months, whereas the median overall survival (OS) was 8.8 months, 14.6 months, and 18 months. The overall response rate (partial and complete) for the GBM, AA, and AO patients was 31%, 46%, and 46%, respectively. Grade 3/4 toxicities included neutropenia (1.1%), thrombocytopenia (3.6%), and anemia (0.3%) (graded according to the World Health Organization grading system).
  
  
  CONCLUSIONS
  Twice-daily dosing may enhance the efficacy of temozolomide in the treatment of recurrent gliomas without increasing toxicity. This regimen compares favorably with other dosing schedules of temozolomide reported in the literature.
authors.affiliation: Department of Neurology, New York Presbyterian, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY 10032, USA. cb116@columbia.edu
authors.forename: Casilda
authors.initials: C
authors.lastname: Balmaceda
authors.forename: David
authors.initials: D
authors.lastname: Peereboom
authors.forename: Susan
authors.initials: S
authors.lastname: Pannullo
authors.forename: Ying Kuen K
authors.initials: YK
authors.lastname: Cheung
authors.forename: Paul G
authors.initials: PG
authors.lastname: Fisher
authors.forename: Jane
authors.initials: J
authors.lastname: Alavi
authors.forename: Michael
authors.initials: M
authors.lastname: Sisti
authors.forename: Johnson
authors.initials: J
authors.lastname: Chen
authors.forename: Robert L
authors.initials: RL
authors.lastname: Fine
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage* / Q000633:toxicity; D001932:Brain Neoplasms / Q000188:drug therapy*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide