Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors

作者：Cives M; Ghayouri M; Morse B; Brelsford M; Black M; Rizzo A; Meeker A; Stro**erg J

来源：Endocrine-Related Cancer, 2016, 23(9): 759-767.

DOI：10.1530/ERC-16-0147

• predictive factors
• MGMT
• ALT
• DAXX
• ATRX

The capecitabine and temozolomide (CAPTEM) regimen is active in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs), with response rates ranging from 30 to 70%. Small retrospective studies suggest that O-6-methylguanine DNA methyltransferase (MGMT) deficiency predicts response to temozolomide. High tumor proliferative activity is also commonly perceived as a significant predictor of response to cytotoxic chemotherapy. It is unclear whether chromosomal instability (CIN), which correlates with alternative lengthening of telomeres (ALT), is a predictive factor. In this study, we evaluated 143 patients with advanced pNET who underwent treatment with CAPTEM for radiographic and biochemical response. MGMT expression (n = 52), grade (n = 128) and ALT activation (n = 46) were investigated as potential predictive biomarkers. Treatment with CAPTEM was associated with an overall response rate (ORR) of 54% by RECIST 1.1. Response to CAPTEM was not influenced by MGMT expression, proliferative activity or ALT pathway activation. Based on these results, no biomarker-driven selection criteria for use of the CAPTEM regimen can be recommended at this time.

• 出版日期2016-9