title: A phase II study of thalidomide in patients with brain metastases from malignant melanoma.
abstract: BACKGROUND
  Brain metastases develop in nearly half of the patients with advanced melanoma and in 15 to 20% of these patients CNS is the first site of relapse. Overall median survival is short, ranging from 2 to 4 months. Thalidomide has antiangiogenic and immunomodulatory effects. Results obtained in prior trials indicate that Thalidomide acts as a cytostatic agent in metastatic melanoma. We evaluated single agent antitumour activity and toxicity of Thalidomide in a phase II setting in patients with brain metastases associated with metastatic melanoma.
  
  
  METHODS
  Patients with measurable metastatic melanoma in progression and with PS < or = 2 were enrolled in the study. Thalidomide was given orally. Dose was escalated over 4 weeks from 100 mg/day to 400 mg/day. Primary objective of the study was to determine response rate, according to RECIST. Secondary objectives were to estimate time to progression, overall survival and to evaluate tolerability of the regimen.
  
  
  RESULTS
  Twenty five men and 11 women were enrolled in the study, median age 48 years. Among 36 eligible patients 35 were evaluable for response. None of the patients obtained a response in brain metastases. Three patients obtained a partial response in extracranial lesions. Toxicity was acceptable and manageably. Median time to progression and overall survival time was 1.7 and 3.1 months, respectively.
  
  
  CONCLUSIONS
  There were no objective responses in the brain but single agent Thalidomide has some activity in melanoma patients with brain metastases. It has encouraged us to investigate Thalidomide in combination with Temozolomide, a very lipophilic agent, in this group of patients.
authors.affiliation: Department of Oncology, Odense University Hospital, Odense C, Denmark. lene.vestermark@ouh.regionsyddanmark.dk
authors.forename: Lene W
authors.initials: LW
authors.lastname: Vestermark
authors.forename: Susanne
authors.initials: S
authors.lastname: Larsen
authors.forename: Birgit
authors.initials: B
authors.lastname: Lindeløv
authors.forename: Lars
authors.initials: L
authors.lastname: Bastholt
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008875:Middle Aged; D009367:Neoplasm Staging; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D013792:Thalidomide / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D013792:Thalidomide