title: Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors.
abstract: OBJECTIVE
  A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors.
  
  
  METHODS
  Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m(2)) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of O(6)-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n=23) and compared with response to temozolomide.
  
  
  RESULTS
  Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with O(6)-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses.
  
  
  CONCLUSIONS
  Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Ekeblad
authors.forename: Anders
authors.initials: A
authors.lastname: Sundin
authors.forename: Eva Tiensuu
authors.initials: ET
authors.lastname: Janson
authors.forename: Staffan
authors.initials: S
authors.lastname: Welin
authors.forename: Dan
authors.initials: D
authors.lastname: Granberg
authors.forename: Henrik
authors.initials: H
authors.lastname: Kindmark
authors.forename: Kristina
authors.initials: K
authors.lastname: Dunder
authors.forename: Gordana
authors.initials: G
authors.lastname: Kozlovacki
authors.forename: Håkan
authors.initials: H
authors.lastname: Orlefors
authors.forename: Mattias
authors.initials: M
authors.lastname: Sigurd
authors.forename: Kjell
authors.initials: K
authors.lastname: Oberg
authors.forename: Barbro
authors.initials: B
authors.lastname: Eriksson
authors.forename: Britt
authors.initials: B
authors.lastname: Skogseid
mesh_terms: D000368:Aged; D001984:Bronchial Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002276:Carcinoid Tumor / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D000077204:Temozolomide; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D003606:Dacarbazine; D000077204:Temozolomide