title: Analysis of potential response predictors to capecitabine/temozolomide in metastatic pancreatic neuroendocrine tumors.
abstract: The capecitabine and temozolomide (CAPTEM) regimen is active in the treatment of metastatic pancreatic neuroendocrine tumors (pNETs), with response rates ranging from 30 to 70%. Small retrospective studies suggest that O(6)-methylguanine DNA methyltransferase (MGMT) deficiency predicts response to temozolomide. High tumor proliferative activity is also commonly perceived as a significant predictor of response to cytotoxic chemotherapy. It is unclear whether chromosomal instability (CIN), which correlates with alternative lengthening of telomeres (ALT), is a predictive factor. In this study, we evaluated 143 patients with advanced pNET who underwent treatment with CAPTEM for radiographic and biochemical response. MGMT expression (n=52), grade (n=128) and ALT activation (n=46) were investigated as potential predictive biomarkers. Treatment with CAPTEM was associated with an overall response rate (ORR) of 54% by RECIST 1.1. Response to CAPTEM was not influenced by MGMT expression, proliferative activity or ALT pathway activation. Based on these results, no biomarker-driven selection criteria for use of the CAPTEM regimen can be recommended at this time.
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cives
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: M
authors.initials: M
authors.lastname: Ghayouri
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: B
authors.initials: B
authors.lastname: Morse
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: M
authors.initials: M
authors.lastname: Brelsford
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
authors.forename: M
authors.initials: M
authors.lastname: Black
authors.affiliation: Department of PathologyJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: A
authors.initials: A
authors.lastname: Rizzo
authors.affiliation: Department of PathologyJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: A
authors.initials: A
authors.lastname: Meeker
authors.affiliation: Department of Gastrointestinal OncologyH. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA jonathan.strosberg@moffitt.org.
authors.forename: J
authors.initials: J
authors.lastname: Strosberg
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology / Q000627:therapeutic use*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069287:Capecitabine / Q000494:pharmacology / Q000627:therapeutic use*; D056970:Co-Repressor Proteins; D015254:DNA Modification Methylases / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D018358:Neuroendocrine Tumors / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016615:Telomere; D000077204:Temozolomide; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D000075924:X-linked Nuclear Protein / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000964:Antimetabolites, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D025521:Tumor Suppressor Proteins; D000069287:Capecitabine; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C092332:ATRX protein, human; D000075924:X-linked Nuclear Protein; D045643:DNA Repair Enzymes; D000077204:Temozolomide
keywords: ALT; ATRX; DAXX; MGMT; predictive factors