Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study

Davide Campana, Thomas Walter, Sara Pusceddu, Fabio Gelsomino, Emmanuelle Graillot, Natalie Prinzi, Andrea Spallanzani, Michelangelo Fiorentino, Marc Barritault, Filippo Dall'Olio, Nicole Brighi, Guido Biasco

Research output: Contribution to journalArticlepeer-review

Abstract

PURPOSE: Temozolomide (TEM) based therapy has been reported being effective in the treatment of metastatic neuroendocrine neoplasms (NEN), with response rates ranging from 30 to 70%. Among patients affected by advanced glioblastoma or melanoma and treated with TEM, loss of tumoral O6-methylguanine DNA methyltransferase (MGMT) is correlated with improved survival. In NEN patients, the role of MGMT deficiency in predicting clinical outcomes of TEM treatment is still under debate.

METHODS: In this study we evaluated 95 patients with advanced NENs undergoing treatment with TEM-based therapy. MGMT promoter methylation status was evaluated with two techniques: methylation specific-polymerase chain reaction or pyrosequencing.

RESULTS: Treatment with TEM-based therapy was associated with an overall response rate of 27.4% according to RECIST criteria (51.8% of patients with and 17.7% without MGMT promoter methylation). Response to therapy, progression free survival and overall survival was correlated to MGMT status at univariate and multivariate analysis. Methylation of MGMT promoter could be a strong predictive factor of objective response and an important prognostic factor of a longer PFS and OS.

CONCLUSION: According to our results, MGMT methylation status, evaluated with methylation specific-polymerase chain reaction or pyrosequencing, should have an important role in patients with metastatic NENs, in order to guide therapeutic options. These results need further confirmation with prospective studies.

Original languageEnglish
Pages (from-to)490-498
Number of pages9
JournalEndocrine
Volume60
Issue number3
DOIs
Publication statusPublished - Jun 2018

Keywords

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Methylation
  • DNA Modification Methylases/genetics
  • DNA Repair Enzymes/genetics
  • Female
  • Humans
  • Lung Neoplasms/drug therapy
  • Male
  • Middle Aged
  • Neuroendocrine Tumors/drug therapy
  • Pancreatic Neoplasms/drug therapy
  • Pharmacogenetics
  • Prognosis
  • Promoter Regions, Genetic
  • Retrospective Studies
  • Survival Rate
  • Temozolomide/therapeutic use
  • Treatment Outcome
  • Tumor Suppressor Proteins/genetics
  • Young Adult

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