MGMT expression predicts response to temozolomide in pancreatic neuroendocrine tumors.
Fiche publication
Date publication
août 2016
Journal
Endocrine-related cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VERNEREY Dewi
Tous les auteurs :
Cros J, Hentic O, Rebours V, Zappa M, Gille N, Theou-Anton N, Vernerey D, Maire F, Lévy P, Bedossa P, Paradis V, Hammel P, Ruszniewski P, Couvelard A
Lien Pubmed
Résumé
Temozolomide (TEM) showed encouraging results in well-differentiated pancreatic neuroendocrine tumors (WDPNETs). Low O(6)-methylguanine-DNA methyltransferase (MGMT) expression and MGMT promoter methylation within tumors correlate with a better outcome under TEM-based chemotherapy in glioblastoma. We aimed to assess whether MGMT expression and MGMT promoter methylation could help predict the efficacy of TEM-based chemotherapy in patients with WDPNET. Consecutive patients with progressive WDPNET and/or liver involvement over 50% who received TEM between 2006 and 2012 were retrospectively studied. Tumor response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 guidelines. Nuclear expression of MGMT was assessed by immunochemistry (H-score, 0-300) and MGMT promoter methylation by pyrosequencing. Forty-three patients (21 men, 58years (27-84)) with grade 1 WDPNET (n=6) or 2 (n=36) were analyzed. Objective response, stable disease, and progression rates were seen in 17 patients (39.5%), 18 patients (41.9%), and 8 patients (18.6%), respectively. Low MGMT expression (≤50) was associated with radiological objective response (P=0.04) and better progression-free survival (PFS) (HR=0.35 (0.15-0.81), P=0.01). Disease control rate at 18months of treatment remained satisfying with an MGMT score up to 100 (74%) but dropped with a higher expression. High MGMT promoter methylation was associated with a low MGMT expression and longer PFS (HR=0.37 (0.29-1.08), P=0.05). Low MGMT score (≤50) appears to predict an objective tumor response, whereas an intermediate MGMT score (50-100) seems to be associated with prolonged stable disease.
Mots clés
Aged, Antimetabolites, Antineoplastic, pharmacology, Antineoplastic Agents, Alkylating, pharmacology, Antineoplastic Combined Chemotherapy Protocols, pharmacology, Capecitabine, pharmacology, DNA Methylation, DNA Modification Methylases, genetics, DNA Repair Enzymes, genetics, Dacarbazine, analogs & derivatives, Disease-Free Survival, Female, Humans, Male, Middle Aged, Neuroendocrine Tumors, drug therapy, Pancreatic Neoplasms, drug therapy, Prognosis, Promoter Regions, Genetic, Treatment Outcome, Tumor Suppressor Proteins, genetics
Référence
Endocr. Relat. Cancer. 2016 08;23(8):625-33