Metronomic combination therapy including temozolamide, bevacizumab and somatostatin analogue for the treatment of malignant gastroenteropancreatic neuroendocrine tumors Abstract #55

Introduction: Malignant gastroenteropancreatic neuroendocrine tumors (GEPNETS), mainly carcinoids, are not considered to be particularly chemotherapy-sensitive to conventional chemotherapeutic schemes. Long-standing evidence suggests these tumors to be highly vascularised and responsive to antiangiogenic strategies. Newest reports demonstrate benefit by the use of temozolamide, an oral alkylating agent similar to intravenous dacarbazine. The DNA repair enzyme O6-alkylguanine–DNA alkyltransferase (AGAT) confers cancer cell resistance to O6-alkylating agents such as temozolamide through its ability to remove methyl/alkyl groups from the O6-position of guanine, thus correcting drug-induced DNA damage.
Aim(s): We investigated a novel combination of drugs including daily low dose temozolamide chemotherapy, bevacizumab a monoclonal antibody targeting the vascular endothelial growth factor and somatostatin analogue.
Materials and methods: From July 2008 to June 2009, 13 patients with previously treated and progressive metastatic GEPNETs received oral temozolamide 100 mg/day, intravenous bevacizumab 7.5 mg/m2 every three weeks and the long-acting somatostatin analogue octreotide 30 mg subcutaneously every three weeks (TeBeSa). There were nine men (median age 64 years, range 47-78) with four functioning and nine non-functioning tumors (seven pancreatic, four small intestine, one gastric, and one of unknown primary). Before TeBeSa therapy, nine patients had received first-line therapy (Cisplatin/etoposide: 6pts, streptozotocin/5-FU: 2 pts and Everolimus: 1pt), three patients two lines and one patient three lines of therapy. There were no available archived tissues for testing AGAT expression with immunohistochemistry in any of these patients.
Conference: 7th Annual ENETS Conference (2010)
Category: Clinical
Presenting Author: DR Anna Koumarianou

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