1. Correlation between MGMT promoter methylation and response to temozolomide-based therapy in neuroendocrine neoplasms: an observational retrospective multicenter study.
- Author
-
Campana, Davide, Walter, Thomas, Pusceddu, Sara, Gelsomino, Fabio, Graillot, Emmanuelle, Prinzi, Natalie, Spallanzani, Andrea, Fiorentino, Michelangelo, Barritault, Marc, Dall’Olio, Filippo, Brighi, Nicole, and Biasco, Guido
- 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% withoutMGMT promoter methylation). Response to therapy, progression free survival and overall survival was correlated to MGMT status at univariate and multivariate analysis. Methylation ofMGMT 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. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF