title: Phase II study of fenretinide (NSC 374551) in adults with recurrent malignant gliomas: A North American Brain Tumor Consortium study.
abstract: OBJECTIVE
  Fenretinide induces apoptosis in malignant gliomas in vitro. This two-stage phase II trial was conducted to determine the efficacy of fenretinide in adults with recurrent malignant gliomas.
  
  
  METHODS
  Twenty-two patients with anaplastic gliomas (AG) and 23 patients with glioblastoma (GBM) whose tumors had recurred after radiotherapy and no more than two chemotherapy regimens were enrolled. Fenretinide was given orally on days 1 to 7 and 22 to 28 in 6-week cycles in doses of 600 or 900 mg/m(2) bid.
  
  
  RESULTS
  Six of 21 (29%) patients in the AG arm and two of 23 (9%) patients in the GBM arm had stable disease at 6 months. One patient with AG treated at 900 mg/m(2) bid dosage had a partial radiologic response. Median progression-free survival (PFS) was 6 weeks for the AG arm and 6 weeks for the GBM arm. PFS at 6 months was 10% for the AG arm and 0% for the GBM arm. Grade 1 or 2 fatigue, dryness of skin, anemia, and hypoalbuminemia were the most frequent toxicities reported. The trial was closed after the first stage because of the inadequate activity at the fenretinide doses used. The first-administration mean plasma C(max) for fenretinide was 832 +/- 360 ng/mL at the 600 mg/m(2) bid dosage and 1,213 +/- 261 ng/mL at the 900 mg/m(2) bid dosage.
  
  
  CONCLUSIONS
  Fenretinide was inactive against recurrent malignant gliomas at the dosage used in this trial. However, additional studies using higher doses of the agent are warranted based on the tolerability of the agent and the potential for activity of a higher fenretinide dosage, as suggested in this trial.
authors.affiliation: Department of Neuro-Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit 431, Houston TX 77030, USA. vpuduval@mdanderson.org
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Puduvalli
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Hess
authors.forename: John G
authors.initials: JG
authors.lastname: Kuhn
authors.forename: Morris D
authors.initials: MD
authors.lastname: Groves
authors.forename: Victor A
authors.initials: VA
authors.lastname: Levin
authors.forename: James
authors.initials: J
authors.lastname: Zwiebel
authors.forename: Susan M
authors.initials: SM
authors.lastname: Chang
authors.forename: Timothy F
authors.initials: TF
authors.lastname: Cloughesy
authors.forename: Larry
authors.initials: L
authors.lastname: Junck
authors.forename: Patrick
authors.initials: P
authors.lastname: Wen
authors.forename: Frank
authors.initials: F
authors.lastname: Lieberman
authors.forename: Charles A
authors.initials: CA
authors.lastname: Conrad
authors.forename: Mark R
authors.initials: MR
authors.lastname: Gilbert
authors.forename: Christina A
authors.initials: CA
authors.lastname: Meyers
authors.forename: Vivien
authors.initials: V
authors.lastname: Liu
authors.forename: Minesh P
authors.initials: MP
authors.lastname: Mehta
authors.forename: M Kelly
authors.initials: MK
authors.lastname: Nicholas
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D005260:Female; D017313:Fenretinide / Q000008:administration & dosage / Q000627:therapeutic use*; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D017313:Fenretinide