TY - JOUR
T1 - O6-methylguanine-DNA methyltransferase (MGMT) status in neuroendocrine tumors
T2 - a randomized phase II study (MGMT-NET)
AU - for the MGMT-NET investigators
AU - Lemelin, Annie
AU - Barritault, Marc
AU - Hervieu, Valérie
AU - Payen, Léa
AU - Péron, Julien
AU - Couvelard, Anne
AU - Cros, Jérome
AU - Scoazec, Jean Yves
AU - Bin, Sylvie
AU - Villeneuve, Laurent
AU - Lombard-Bohas, Catherine
AU - Walter, Thomas
N1 - Publisher Copyright:
© 2019 Editrice Gastroenterologica Italiana S.r.l.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - Introduction: Neuroendocrine tumors (NETs) are rare, but their incidence is rising. Alkylating agents (ALKY), temozolomide and streptozotocin, are the main chemotherapies used for advanced pancreatic NETs. According to retrospective data, O6-methylguanine-DNA methyltransferase (MGMT) status appears to be a predictive factor of the response to ALKY. Aims: The main objective is to evaluate the value of tumor MGMT promoter (pMGMT) methylation in the prediction of the objective response (OR) at 3 months in patients treated with ALKY. Secondly, we will evaluate the value of MGMT immunohistochemistry and the efficacy of treatment with ALKY vs. oxaliplatin-based chemotherapy (Ox). Materials and methods: A national, prospective, open-label, randomized, controlled and multicenter trial was designed. Main inclusion criteria are: adult patients with well-differentiated advanced duodeno-pancreatic, lung, or unknown primitive NETs with a validated indication for chemotherapy. pMGMT methylation will be assessed by pyrosequencing, but an ancillary study will compare this technique with others ones including MGMT immunohistochemistry. Results: A total of 104 patients will be randomly assigned (1:1 for unmethylated or 2:1 for methylated pMGMT NETs) to either the ALKY arm or to the Ox arm. Conclusion: Recruitment started on October 16, 2018 (NCT03217097) and will be open in 21 centers in France.
AB - Introduction: Neuroendocrine tumors (NETs) are rare, but their incidence is rising. Alkylating agents (ALKY), temozolomide and streptozotocin, are the main chemotherapies used for advanced pancreatic NETs. According to retrospective data, O6-methylguanine-DNA methyltransferase (MGMT) status appears to be a predictive factor of the response to ALKY. Aims: The main objective is to evaluate the value of tumor MGMT promoter (pMGMT) methylation in the prediction of the objective response (OR) at 3 months in patients treated with ALKY. Secondly, we will evaluate the value of MGMT immunohistochemistry and the efficacy of treatment with ALKY vs. oxaliplatin-based chemotherapy (Ox). Materials and methods: A national, prospective, open-label, randomized, controlled and multicenter trial was designed. Main inclusion criteria are: adult patients with well-differentiated advanced duodeno-pancreatic, lung, or unknown primitive NETs with a validated indication for chemotherapy. pMGMT methylation will be assessed by pyrosequencing, but an ancillary study will compare this technique with others ones including MGMT immunohistochemistry. Results: A total of 104 patients will be randomly assigned (1:1 for unmethylated or 2:1 for methylated pMGMT NETs) to either the ALKY arm or to the Ox arm. Conclusion: Recruitment started on October 16, 2018 (NCT03217097) and will be open in 21 centers in France.
KW - Alkylating agents
KW - Clinical trial
KW - Neuroendocrine
KW - O6-Methylguanine-DNA methyltransferase
UR - http://www.scopus.com/inward/record.url?scp=85062023690&partnerID=8YFLogxK
U2 - 10.1016/j.dld.2019.02.001
DO - 10.1016/j.dld.2019.02.001
M3 - Article
C2 - 30824408
AN - SCOPUS:85062023690
SN - 1590-8658
VL - 51
SP - 595
EP - 599
JO - Digestive and Liver Disease
JF - Digestive and Liver Disease
IS - 4
ER -