Combination therapy with capecitabine and temozolomide in patients with low and high grade neuroendocrine tumors, with an exploratory analysis of O 6-methylguanine DNA methyltransferase as a biomarker for response

Oncotarget. 2017 Oct 24;8(61):104046-104056. doi: 10.18632/oncotarget.22001. eCollection 2017 Nov 28.


Recent advances in the treatment of neuroendocrine tumors (NET), including the combination regimen of capecitabine and temozolomide (CAPTEM), have mostly focused on grade 1 and 2 pancreatic neuroendocrine tumors (pNET). We undertook a retrospective review of 38 patients with advanced NET treated with CAPTEM, including patients with non-pancreatic tumors as well as grade 2 and 3 tumors. O6-methylguanine DNA methyltransferase (MGMT) expression was assessed as a predictive biomarker. We found that CAPTEM demonstrated activity in patients with all grades and in pNET and non-pNET. Median progression free survival (mPFS) was 13.0 months (95% CI: 5.6-17.0) and median overall survival (mOS) 29.3 months (95% CI 17.7 - 45.3). Among evaluable patients, there were 11 (38%) partial responses, 15 (52%) stable disease, and 3 (10%) progressive disease for a disease control rate of 90%. A higher rate of partial responses occurred in patients whose tumors had low levels of MGMT expression (63%) compared to intermediate-high (17%) (p=0.19). Our results show that CAPTEM therapy is active in patients with NET including in previously treated patients and in those with poorly-differentiated histology. We observed a trend towards increased response rate, median PFS, and median OS in patients whose tumors had low MGMT protein expression.

Keywords: MGMT; capecitabine; immunohistochemistry; neuroendocrine tumors; temozolomide.