title: Phase II study of the antiangiogenesis agent thalidomide in recurrent or metastatic squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  Thalidomide has been shown to have antiangiogenic effects in preclinical models as well as a significant antitumor effect in hematologic tumors such as multiple myeloma. The authors performed this Phase II study to determine the activity, toxicity profile, and antiangiogenic effect of thalidomide in patients with locoregionally recurrent or metastatic squamous cell carcinoma of the head and neck.
  
  
  METHODS
  Twenty-one patients with recurrent or metastatic squamous cell carcinoma of the head and neck were treated with single-agent thalidomide. All patients had received radiation therapy, and most had undergone surgery (95%) and/or chemotherapy (90%). Thalidomide was initiated at 200 mg;3>daily and increased to a target dose of 1000 mg daily. Patients continued treatment until disease progression, unacceptable toxicity, or death occurred.
  
  
  RESULTS
  All 21 patients eventually developed progressive disease. Median time to progression was 50 days (95% confidence interval, 28-70), with median overall survival time of 194 days (95% lower confidence boundary, 151), similar to the progression and survival times reported for this patient group with other agents. Thalidomide was generally well tolerated, with few patients experiencing Grades 3 to 4 toxicities. Serum vascular endothelial growth factor and basic fibroblast growth factor levels increased in six of seven patients, for whom paired serum samples were available and all of whom had progressive disease.
  
  
  CONCLUSIONS
  In this heavily pretreated population of patients with advanced squamous cell carcinoma of the head and neck, thalidomide does not appear to have single-agent antitumor activity. Further evaluation of the mechanism of action of thalidomide is indicated. Potentially, future evaluations of thalidomide may be performed in combination with other antiangiogenic or cytotoxic agents in patients with earlier stage disease or in patients with minimal residual disease.
authors.affiliation: Department of Thoracic and Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: J E
authors.initials: JE
authors.lastname: Tseng
authors.forename: B S
authors.initials: BS
authors.lastname: Glisson
authors.forename: F R
authors.initials: FR
authors.lastname: Khuri
authors.forename: D M
authors.initials: DM
authors.lastname: Shin
authors.forename: J N
authors.initials: JN
authors.lastname: Myers
authors.forename: A K
authors.initials: AK
authors.lastname: El-Naggar
authors.forename: J S
authors.initials: JS
authors.lastname: Roach
authors.forename: L E
authors.initials: LE
authors.lastname: Ginsberg
authors.forename: P F
authors.initials: PF
authors.lastname: Thall
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Teddy
authors.forename: K N
authors.initials: KN
authors.lastname: Lawhorn
authors.forename: R E
authors.initials: RE
authors.lastname: Zentgraf
authors.forename: G D
authors.initials: GD
authors.lastname: Steinhaus
authors.forename: J M
authors.initials: JM
authors.lastname: Pluda
authors.forename: J L
authors.initials: JL
authors.lastname: Abbruzzese
authors.forename: W K
authors.initials: WK
authors.lastname: Hong
authors.forename: R S
authors.initials: RS
authors.lastname: Herbst
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016019:Survival Analysis; D013792:Thalidomide / Q000009:adverse effects / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide