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

M. Cives, M. Ghayouri, B. Morse, M. Brelsford, M. Black, A. Rizzo, Alan Keith Meeker, J. Strosberg

Research output: Contribution to journalArticle

Abstract

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 O6-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.

Original languageEnglish (US)
Pages (from-to)759-767
Number of pages9
JournalEndocrine-Related Cancer
Volume23
Issue number9
DOIs
StatePublished - 2016

Fingerprint

temozolomide
Neuroendocrine Tumors
Telomere Homeostasis
Methyltransferases
DNA
Biomarkers
Chromosomal Instability
Patient Selection
Capecitabine
Therapeutics
Retrospective Studies

Keywords

  • ALT
  • ATRX
  • DAXX
  • MGMT
  • Predictive factors

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research

Cite this

Cives, M., Ghayouri, M., Morse, B., Brelsford, M., Black, M., Rizzo, A., ... Strosberg, J. (2016). Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. Endocrine-Related Cancer, 23(9), 759-767. https://doi.org/10.1530/ERC-16-0147

Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. / Cives, M.; Ghayouri, M.; Morse, B.; Brelsford, M.; Black, M.; Rizzo, A.; Meeker, Alan Keith; Strosberg, J.

In: Endocrine-Related Cancer, Vol. 23, No. 9, 2016, p. 759-767.

Research output: Contribution to journalArticle

Cives, M. ; Ghayouri, M. ; Morse, B. ; Brelsford, M. ; Black, M. ; Rizzo, A. ; Meeker, Alan Keith ; Strosberg, J. / Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors. In: Endocrine-Related Cancer. 2016 ; Vol. 23, No. 9. pp. 759-767.
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