Dear Editor

Neuroendocrine tumours (NETs) are highly vascularised tumours that express high levels of the vascular endothelial growth factor (VEGF) ligand together with its receptor VEGFR (Modlin et al. 2008). Although advanced NETs may exhibit a 30–40% response rate to combination chemotherapeutic approaches, the response to single-agent chemotherapy is only 10% (Modlin et al. 2008). Bevacizumab (BVZ; Avastin, Roche, Basle, Switzerland), an anti-VEGF humanised monoclonal antibody, has been shown to exert objective tumour responses and improvement in median time to progression (TTP) in advanced carcinoid tumours (Yao et al. 2008). Additionally, a recently published study reported that temozolomide (TMZ), an oral chemotherapy derivative of dacarbazine, at a dose of 200 mg/m² on first 5 days of each 28-day cycle may exert a significant effect on NETs (Ekeblad et al. 2007). A previous report that examined a variety of NETs suggested that the combination of BVZ and TMZ can be safely administered and shows promising activity in patients who had failed to prior treatments (Kulke et al. 2006a). Additionally, there is growing interest on regimens that introduce continuous low-dose TMZ administration as protracted low-dose TMZ regimens may deplete O6-methylguanine DNA methyltransferase (MGMT), an important factor in cases of TMZ resistance and/or inhibit endothelial cell proliferation and formation of tumour vasculature via the so-called metronomic effect (Tolcher et al. 2003, Lam et al. 2007). Although the exact mechanism of action of somatostatin analogues is not well understood, a long-standing hypothesis based on preclinical experiments suggests that they exert an antiangiogenic effect (Grozinsky-Glasberg et al. 2008).

Given the high degree of endothelial proliferation, high vascular permeability and high expression of pro-angiogenic growth factors such as VEGF in NETs, angiogenesis inhibition by multiple pathways may be a rational treatment strategy for these tumours. We …