O6-Methylguanine DNA Methyltransferase Status Does Not Predict Response or Resistance to Alkylating Agents in Well-Differentiated Pancreatic Neuroendocrine Tumors.

Journal Article (Journal Article)

OBJECTIVES: Alkylating agents have activity in well-differentiated pancreatic neuroendocrine tumors (WD panNETs). In glioblastoma multiforme, decreased activity of O-methylguanine DNA methyltransferase (MGMT) predicts response; in panNETs, MGMT relevance is unknown. METHODS: We identified patients with WD panNETs treated with alkylating agents, determined best overall response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, and performed MGMT activity testing. RESULTS: Fifty-six patients were identified; 26 (46%) of the 56 patients experienced partial response, 24 (43%) of 56 experienced stable disease, and 6 (11%) of 56 experienced progression of disease. O-methylguanine DNA methyltransferase status was available for 36 tumors. For tumors with partial response, 10 (67%) of 15 were MGMT deficient, and 5 (33%) of 15 were MGMT intact. For tumors with stable disease, 7 (47%) of 15 were MGMT deficient, and 8 (53%) of 15 were MGMT intact. For tumors with progression of disease, 3 (50%) of 6 were MGMT deficient, and 3 (50%) of 6 were MGMT intact. CONCLUSIONS: We observed response and resistance to alkylating agents in MGMT-deficient and MGMT-intact tumors. O-methylguanine DNA methyltransferase status should not guide alkylating agent therapy in WD panNETs.

Full Text

Duke Authors

Cited Authors

  • Raj, N; Klimstra, DS; Horvat, N; Zhang, L; Chou, JF; Capanu, M; Basturk, O; Do, RKG; Allen, PJ; Reidy-Lagunes, D

Published Date

  • July 2017

Published In

Volume / Issue

  • 46 / 6

Start / End Page

  • 758 - 763

PubMed ID

  • 28609363

Pubmed Central ID

  • PMC5509357

Electronic International Standard Serial Number (EISSN)

  • 1536-4828

Digital Object Identifier (DOI)

  • 10.1097/MPA.0000000000000842


  • eng

Conference Location

  • United States