Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors

Ekeblad S, Eriksson B, Sundin A, Welin S, Granberg D, Kindmark H, Dunder K, Kozlovacki G, Örlefors H, Sigurd M, Öberg K, Janson ET, Skogseid B

Clin Cancer Res. 2007; 13(10): 2986-2991

Abstract

PURPOSE:

A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors.

EXPERIMENTAL DESIGN:

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.

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