title: Oral temozolomide in heavily pre-treated brain metastases from non-small cell lung cancer: phase II study.
abstract: BACKGROUND
  The primary tumour type most likely to metastasize to the brain is lung cancer. In heavily pre-treated patients, limited therapeutic option is available and the results of availability therapies reported in literature are disappointing. The present phase II study was designed to assess the efficacy and safety of temozolomide (TMZ) as palliative treatment for brain metastases (BrM) in NSCLC patients pre-treated with WBRT and at least one line of chemotherapy for metastatic brain disease.
  
  
  METHODS
  Temozolomide was administered orally at 150 mg/mq/day for five consecutive days for the first cycle, doses were increased to 200 mg/mq/day for 5 days every 28 days for subsequent cycles if no grade 3/4 haematological toxicity was observed. Eligibility criteria included cytological or histological confirmed NSCLC; BrM, recurrent or progressing after WBRT and at least one line of chemotherapy. A total of 30 consecutive patients entered the study and received the allocated treatment.
  
  
  RESULTS
  Three patients (10%) achieved an objective response (OR) of BrM with two complete remission. Stable disease and progressive disease were achieved in 3 (10%) and 24 patients (80%), respectively. A correlation between response to TMZ and sensitivity to the previous first line chemotherapy was reported. Time to progression and overall survival were examined both for responder patients and for all included patients. For long-term survivors, we considered the patients who survived >12 months after the start of TMZ. According to this definition, three patients resulted long-term survivors: 2 with OR and 1 with stable brain disease. No grades 3 or 4 toxicity occurred. The total of treatment-related adverse events were mild or moderate (G1-2) in intensity. No patients discontinued TMZ as a result of treatment-related toxicity.
  
  
  CONCLUSIONS
  The results of the present trial clearly demonstrates that TMZ is active and safe in BrM NSCLC patients previously treated with WBRT and at least one line of chemotherapy.
authors.affiliation: Gravina Hospital, Oncology Unit, Caltagirone, Italy.
authors.forename: Carmelo Giannitto
authors.initials: CG
authors.lastname: Giorgio
authors.forename: Dario
authors.initials: D
authors.lastname: Giuffrida
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pappalardo
authors.forename: Antonio
authors.initials: A
authors.lastname: Russo
authors.forename: Daniele
authors.initials: D
authors.lastname: Santini
authors.forename: Placida
authors.initials: P
authors.lastname: Salice
authors.forename: Giusy
authors.initials: G
authors.lastname: Blanco
authors.forename: Sergio
authors.initials: S
authors.lastname: Castorina
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Failla
authors.forename: Roberto
authors.initials: R
authors.lastname: Bordonaro
mesh_terms: D000284:Administration, Oral; D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010166:Palliative Care; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide