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Temozolomide as Monotherapy Is Effective in Treatment of Advanced Malignant Neuroendocrine Tumors

Authors' Affiliations: Departments of ¹ Medical Sciences and ² Radiology, Uppsala University, Uppsala, Sweden

Requests for reprints: Britt Skogseid, Department of Medical Sciences, University Hospital, 75185 Uppsala, Sweden. Phone: 46-1861-10000; Fax: 46-1855-3601; E-mail: Britt.Skogseid{at}medsci.uu.se.

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/m²) 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 O⁶-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 O⁶-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.