title: Phase II evaluation of temozolomide and 13-cis-retinoic acid for the treatment of recurrent and progressive malignant glioma: a North American Brain Tumor Consortium study.
abstract: OBJECTIVE
  Temozolomide (TMZ) and 13-cis-retinoic acid (cRA) have shown activity in prior single-agent trials of recurrent malignant gliomas (MG). This phase II trial evaluated efficacy and toxicity of combination temozolomide and cRA treatment in recurrent MG.
  
  
  METHODS
  Adults with recurrent supratentorial MG for whom surgery, radiation, and/or chemotherapy failed were eligible. Treatment included oral TMZ 150 or 200 mg/m2/d, days 1 through 5, and cRA 100 mg/m2/d, days 1 to 21, every 28 days. Primary end point was progression-free survival at 6 months (PFS 6); secondary end points included response, survival, and PFS12.
  
  
  RESULTS
  Eighty-eight eligible patients (glioblastoma multiforme [n = 40]; anaplastic gliomas [n = 48; astrocytoma, 28; oligodendroglioma, 14; mixed glioma, six]) received treatment. PFS 6 was 43% (95% confidence interval [CI], 33% to 54%) and PFS12 was 16% (95% CI, 10% to 26%). Median overall PFS was 19 weeks (95% CI, 16 to 27 weeks), and median overall survival (OS) was 47 weeks (95% CI, 36 to 58 weeks). OS was 46% (95% CI, 36% to 57%) at 52 weeks and 21% (95% CI, 13% to 31%) at 104 weeks. Of 84 assessable patients, there were two (3%) complete responses and eight (12%) partial responses (complete plus partial response, 15%). Among 499 treatment cycles, the most common grade 3/4 events included granulocytopenia (1.8%), thrombocytopenia (1.4%), and hypertriglyceridemia (1.2%).
  
  
  CONCLUSIONS
  TMZ and cRA were active, exceeding our 20% thresholds for PFS 6 success, assuming 20% improvement over our previously reported database (glioblastoma multiforme: expected, 30%; observed, 32%; anaplastic glioma: expected, 40%; observed, 50%).
authors.affiliation: University of Texas M. D. Anderson Cancer Center, Houston, USA. jaeckle.kurt@mayo.edu.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Jaeckle
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Harry
authors.initials: H
authors.lastname: Greenberg
authors.forename: Howard
authors.initials: H
authors.lastname: Fine
authors.forename: David
authors.initials: D
authors.lastname: Schiff
authors.forename: Ian F
authors.initials: IF
authors.lastname: Pollack
authors.forename: John
authors.initials: J
authors.lastname: Kuhn
authors.forename: Karen
authors.initials: K
authors.lastname: Fink
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
authors.forename: Timothy
authors.initials: T
authors.lastname: Cloughesy
authors.forename: M Kelly
authors.initials: MK
authors.lastname: Nicholas
authors.forename: Susan
authors.initials: S
authors.lastname: Chang
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D015474:Isotretinoin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D015173:Supratentorial Neoplasms / Q000188:drug therapy*; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D015474:Isotretinoin; D000077204:Temozolomide