Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors.
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.
Ekeblad
Sara
S
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Sundin
Anders
A
Janson
Eva Tiensuu
ET
Welin
Staffan
S
Granberg
Dan
D
Kindmark
Henrik
H
Dunder
Kristina
K
Kozlovacki
Gordana
G
Orlefors
Håkan
H
Sigurd
Mattias
M
Oberg
Kjell
K
Eriksson
Barbro
B
Skogseid
Britt
B
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
D003606:Dacarbazine; D000077204:Temozolomide