title: Dose-intensified bi-weekly temozolomide in patients with asymptomatic brain metastases from malignant melanoma: a phase II DeCOG/ADO study.
abstract: BACKGROUND
  Temozolomide has shown some efficacy in metastatic melanoma and recently received extended approval to treat brain tumours. The purpose of this study was to test a dose-intensified regimen of temozolomide in melanoma patients with brain metastases in a prospective, open-label, multicentre phase II trial.
  
  
  METHODS
  Forty-five patients with asymptomatic brain metastases from melanoma were stratified into arm A (no prior chemotherapy; n = 21) and arm B (previous chemotherapy; n = 24). Patients received oral temozolomide either 150 mg/m(2)/day (arm A) or 125 mg/m(2)/day (arm B), days 1-7 and 15-21, every 28 days. The primary study end point was objective response, and secondary end points were overall survival and safety.
  
  
  RESULTS
  Two patients (4.4%) achieved a partial response (PR) in brain metastases (one in each arm), one of them (2.2%) also showing a PR in extracerebral disease. An additional five patients (11.1%; two in arm A, three in arm B) showed disease stabilisation (SD) in brain and other sites. However, 82% revealed progressive disease (PD) already evident 8 weeks after therapy initiation. Median survival time from therapy onset was 3.5 months (range 0.7-8.3; arm B) and 4.3 months (range 1.6-11.8; arm A), P = 0.43. Dose modifications and prolongations of therapy cycles due to toxicity were required in 20% of patients. Grade 3/4 toxicity was observed in one patient only (2.2%).
  
  
  CONCLUSIONS
  Oral administration of temozolomide given bi-weekly is well-tolerated in melanoma patients with cerebral involvement. However, the efficacy is limited, with lower than 5% objective responses observed in brain and extracerebral metastases.
authors.affiliation: Skin Cancer Unit, German Cancer Research Center & University Hospital Mannheim, Department of Dermatology, Mannheim, Germany. d.schadendorf@dkfz.de
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
authors.forename: A
authors.initials: A
authors.lastname: Hauschild
authors.forename: S
authors.initials: S
authors.lastname: Ugurel
authors.forename: A
authors.initials: A
authors.lastname: Thoelke
authors.forename: F
authors.initials: F
authors.lastname: Egberts
authors.forename: M
authors.initials: M
authors.lastname: Kreissig
authors.forename: R
authors.initials: R
authors.lastname: Linse
authors.forename: U
authors.initials: U
authors.lastname: Trefzer
authors.forename: T
authors.initials: T
authors.lastname: Vogt
authors.forename: W
authors.initials: W
authors.lastname: Tilgen
authors.forename: P
authors.initials: P
authors.lastname: Mohr
authors.forename: C
authors.initials: C
authors.lastname: Garbe
mesh_terms: D000328:Adult; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide