title: A phase II study of thalidomide and irinotecan for treatment of glioblastoma multiforme.
abstract: OBJECTIVE
  Irinotecan is a cytotoxic agent with activity against gliomas. Thalidomide, an antiangiogenic agent, may play a role in the treatment of glioblastoma multiforme (GBM). To evaluate the combination of thalidomide and irinotecan, we conducted a phase II trial in adults with newly-diagnosed or recurrent GBM.
  
  
  METHODS
  Thalidomide was given at a dose of 100 mg/day, followed by dose escalation every 2 weeks by 100 mg/day to a target of 400 mg/day. Irinotecan was administered on day 1 of each 3 week cycle. Irinotecan dose was 700 mg/m(2) for patients taking enzyme-inducing anticonvulsants and 350 mg/m(2) for all others. The primary endpoint was tumor response, assessed by MRI. Secondary endpoints were toxicity, progression-free survival, and overall survival.
  
  
  RESULTS
  Twenty-six patients with a median age of 55 years were enrolled, with fourteen evaluable for the primary outcome, although all patients were included for secondary endpoints. One patient (7%) exhibited a partial response after twelve cycles, and eleven patients (79%) had stable disease. The intention to treat group with recurrent disease included 16 patients who had a 6-month PFS of 19% (95% CI: 4-46%) and with newly-diagnosed disease included 10 patients who had a 6-month PFS of 40% (95% CI: 12-74%). Gastrointestinal (GI) toxicity was mild, but six patients (23%) experienced a venous thromboembolic complication. Two patients had Grade 4 treatment-related serious adverse events that required hospitalization. There were no treatment-related deaths.
  
  
  CONCLUSIONS
  The combination of irinotecan and thalidomide has limited activity against GBM. Mild GI toxicity was observed, but venous thromboembolic complications were common.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center Drive, One Medical Center Drive, Lebanon, NH 03756, USA. camilo.e.fadul@hitchcock.org
authors.forename: Camilo E
authors.initials: CE
authors.lastname: Fadul
authors.forename: Linda S
authors.initials: LS
authors.lastname: Kingman
authors.forename: Louise P
authors.initials: LP
authors.lastname: Meyer
authors.forename: Bernard F
authors.initials: BF
authors.lastname: Cole
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Eskey
authors.forename: C Harker
authors.initials: CH
authors.lastname: Rhodes
authors.forename: David W
authors.initials: DW
authors.lastname: Roberts
authors.forename: Herbert B
authors.initials: HB
authors.lastname: Newton
authors.forename: J Marc
authors.initials: JM
authors.lastname: Pipas
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage*
chemical_list: D007166:Immunosuppressive Agents; D013792:Thalidomide; D000077146:Irinotecan; D002166:Camptothecin