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Phase II Study of Temozolomide and Thalidomide in Patients With Metastatic Neuroendocrine Tumors

From the Department of Medical Oncology, Dana-Farber Cancer Institute; Division of Hematology/Oncology, Beth Israel-Deaconess Medical Center; Division of Hematology/Oncology, and Department of Biostatistics, Massachusetts General Hospital; and Channing Laboratory, Brigham and Women’s Hospital, Boston, MA

Address reprint requests to Matthew H. Kulke, MD, Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: matthew_kulke{at}dfci.harvard.edu

Purpose Standard, intravenous chemotherapy regimens for neuroendocrine tumors have been associated with limited response rates and significant toxicity. We evaluated the efficacy of an oral regimen of temozolomide and thalidomide in patients with metastatic carcinoid, pheochromocytoma, or pancreatic neuroendocrine tumors.

Patients and Methods Twenty-nine patients were treated with a combination of temozolomide, administered at a dose of 150 mg/m² for 7 days, every other week, and thalidomide at doses of 50 to 400 mg daily. Patients were followed for evidence of toxicity, biochemical response, radiologic response, and survival.

Results Treatment with temozolomide and thalidomide was associated with an objective biochemical (chromogranin A) response rate of 40%, and a radiologic response rate of 25% (45% among pancreatic endocrine tumors, 33% among pheochromocytomas, and 7% among carcinoid tumors). The median duration of response was 13.5 months, 1-year survival was 79%, and 2-year survival was 61%. The median administered dose of temozolomide was 150 mg/m², and the median administered dose of thalidomide was 100 mg daily. Grade 3-4 toxicities were uncommon, with the exception of grade 3-4 lymphopenia, which developed in 69% of the patient population. Opportunistic infections occurred in three patients (10%) during the time of lymphopenia, and included single cases of Pneumocystis carinii pneumonia, disseminated varicella zoster virus, and herpes simplex virus.

Conclusion Orally administered temozolomide and thalidomide seems to be an active regimen for the treatment of neuroendocrine tumors. In this 29-patient study, this regimen appeared more active in pancreatic endocrine tumors than in carcinoid tumors.

Supported by Schering-Plough and Celgene, in part by NIH Grants No. K23 CA 093401, K30 HL04095 (M.H.K.), and gifts from Dr Raymond and Beverly Sackler, the Caring for Carcinoid Foundation, and the Stephen and Caroline Kaufer Fund for Neuroendocrine Tumor Research.

Presented in part at the 2003 Chemotherapy Foundation Symposium, New York, NY, November 12-15, 2003.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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