Oral regimen for metastatic neuroendocrine tumours

Abstract

An oral regimen of temozolomide and thalidomide seems to be active against metastatic neuroendocrine tumours, according to a team from Dana-Farber Cancer Institute, Boston, MA, USA (J Clin Oncol 2006; 24: 401–06). “Neuroendocrine tumours are highly vascular, and the use of thalidomide was based on its putative antiangiogenic effects”, says lead investigator Matthew Kulke. Temozolomide is a less-toxic analogue of dacarbazine. In a phase II study of 29 patients with metastatic carcinoid, phaeochromocytoma, or pancreatic neuroendocrine tumours, 40% had an objective biochemical response, as measured by concentration of chromogranin—a surrogate marker of antitumour activity. Radiological response was 45% for patients with pancreatic endocrine tumours, 33% for phaeochromocytomas, and 7% for carcinoid tumours. Median duration of response was 13·5 months, 1-year survival was 79%, and 2-year survival was 61%. Grade 3–4 toxic effects were uncommon, apart from lymphopenia in 69% of patients. “We believe that the combination of temozolomide and thalidomide is an active oral regimen for the treatment of advanced neuroendocrine tumors, and represents a reasonable treatment alternative to older, intravenous regimens”, says Kulke. “Like previous intravenous regimens, this one appears to be more active in pancreatic than in other neuroendocrine tumour types, although we do not know why that would be”, adds Kulke. Manfred Lutz, Caritasklinik St Theresia, Saarbrucken, Germany, comments that “the main merit of the study is that it demonstrates the activity of an oral regimen in neuroendocrine tumours and it seems to be fairly well tolerated”. However, he remains to be convinced about the contribution of thalidomide. ”We know that chemotherapy alone, with streptozotocin or dacarbazine-based regimens, yields responses in around a third of patients, which is quite similar to the results reported here. Therefore, it remains unclear if the antiangiogenic activity of thalidomide adds anything.” He adds: “I would like to see another phase II trial with temozolomide given as a single agent to a study population with a clear focus on proliferating tumours”. Gregory Friberg, University of Chicago, IL, USA, shares the concern over the effectiveness of thalidomide, and draws attention to the frequency of lymphopenia and the potential for long-term immunosuppressive effects; nevertheless, he acknowledges that the new regimen seems to be acutely better tolerated than some alternatives.