title: Teniposide for brain metastases of small-cell lung cancer: a phase II study. European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group.
abstract: OBJECTIVE
  Here we report the results of a phase II study of teniposide, one of the most active drugs against small-cell lung cancer (SCLC), in patients with brain metastases.
  
  
  METHODS
  Patients with SCLC who presented with brain metastases at diagnosis (n = 11) or during follow-up evaluation after treatment (n = 69) were treated with teniposide at a dose of 150 mg/m2 intravenously on days 1, 3, and 5 at 3-week intervals in an outpatient setting. Response in the brain was evaluated by brain computed tomography (CT) after two, six, and 12 courses.
  
  
  RESULTS
  In 26 of 80 assessable patients, an intracranial response was seen, with a response rate of 33% (95% confidence interval, 22% to 44%). The median response duration was 5.4 months for patients with a complete response (CR) and 4.2 months for patients with a partial response (PR). Patients who required corticosteroids for peritumoral edema had a significantly lower response rate than patients who did not receive corticosteroids. Neurologic function at the start of treatment had a significant influence (neurologic function 1 better than 2, respectively, better than 3 and 4; P < .001), as did the number of cycles of previous chemotherapy (0 better than 1 to 5 cycles, respectively, better than > 5 cycles; P = .043). Grade 3/4 leukocytopenia and thrombocytopenia were seen in 3% and 39%, respectively, of 80 patients. Toxicity-related death was seen in eight patients, seven of whom were previously treated with chemotherapy.
  
  
  CONCLUSIONS
  Teniposide is active against brain metastases of SCLC. It is a suitable drug for palliation, especially of patients without extensive pretreatment and with a good neurologic function and performance status. Patients previously treated with cranial radiotherapy are also candidates for this therapy. If systemic chemotherapy is considered for tumor progression outside the brain, radiotherapy of brain metastases might be omitted or delayed pending the effect of chemotherapy. The use of corticosteroids in patients with brain metastases treated with chemotherapy might influence the efficacy of the chemotherapy.
authors.affiliation: Department of Pulmonary Diseases, University Hospital, Free University, Amsterdam, The Netherlands.
authors.forename: P E
authors.initials: PE
authors.lastname: Postmus
authors.forename: E F
authors.initials: EF
authors.lastname: Smit
authors.forename: H
authors.initials: H
authors.lastname: Haaxma-Reiche
authors.forename: N
authors.initials: N
authors.lastname: van Zandwijk
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
authors.forename: E
authors.initials: E
authors.lastname: Quoix
authors.forename: A
authors.initials: A
authors.lastname: Kirkpatrick
authors.forename: T
authors.initials: T
authors.lastname: Sahmoud
authors.forename: G
authors.initials: G
authors.lastname: Giaccone
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D018288:Carcinoma, Small Cell / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000556:secondary*; D016371:Cranial Irradiation; D005060:Europe; D005260:Female; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D012074:Remission Induction; D013713:Teniposide / Q000009:adverse effects / Q000627:therapeutic use*; D013921:Thrombocytopenia / Q000139:chemically induced; D014057:Tomography, X-Ray Computed
chemical_list: D013713:Teniposide