Kulke MH et al. (2006) Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol 24: 401–406

Although medical treatments for hormone-secreting neuroendocrine tumors can help normalize hormone levels, they rarely reduce tumor size. Dacarbazine has shown some promise but is associated with marked adverse effects. Kulke et al., therefore, assessed the efficacy and safety of a combination therapy comprising temozolomide and thalidomide.

This phase II trial evaluated 29 patients with histologically confirmed metastatic tumors. Thalidomide was given daily at a dose of 50–400 mg, whereas 150 mg/m2 temozolomide was administered for 7 days, every other week. Doses of both agents were adjusted in response to adverse effects and the median treatment duration was 7.3 months. Overall, 16 patients discontinued therapy because of toxicity (median time to withdrawal 8.4 months). Serious treatment-related effects included neuropathy, thromobocytopenia, lymphopenia, and opportunistic infections. The radiologic response rate (complete or partial tumor regression) was 25%, with the regimen being most effective against pancreatic neuroendocrine tumors (5 out of 11 patients). The median response duration was 13.5 months. The biologic response rate, assessed by serum CHROMOGRANIN A levels, was 40%. Follow-up was for a median of 26 months. Only four patients experienced progressive disease and the 1-year and 2-year survival rates were 79% and 61%, respectively.

This small trial demonstrates that temozolomide and thalidomide combination therapy could be effective for treating neuroendocrine tumors; nevertheless, larger trials will be necessary to assess the efficacy and safety of this regimen fully.