Anne-Sophie Dussol1, Marie-Odile Joly2,3,4, Cecile Vercherat2, Julien Forestier1, Valérie Hervieu2,3,4, Jean-Yves Scoazec2,3,4, Catherine Lombard-Bohas1, Thomas Walter1,2,4. 1. Department of Digestive Oncology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. 2. Lyon Cancer Research Center (National Institute of Health and Medical Research Joint Research Unit 1052), Laennec Faculty, Lyon, France. 3. Department of Central Anatomy and Pathological Cytology, Edouard Herriot Hospital, Hospices Civils de Lyon, Lyon, France. 4. Claude Bernard University Lyon 1, University of Lyon, Villeurbanne, France.
Abstract
BACKGROUND: The alkylating agents (ALKYs) streptozotocin, dacarbazine, and temozolomide currently are the main drugs used in systemic chemotherapy for neuroendocrine tumors (NETs). The promising activity shown by gemcitabine and oxaliplatin (GEMOX) in previous studies prompted this study 1) to confirm the use of GEMOX in a larger population of NET patients, 2) to compare its efficacy with that of ALKYs, and 3) to explore whether the O(6) -methylguanine-DNA methyltransferase (MGMT) status could help in selecting the chemotherapy regimen. METHODS: One hundred four patients with metastatic NETs (37 pancreatic NETs, 33 gastrointestinal NETs, 23 bronchial NETs, and 11 NETs of other/unknown origin) were treated with GEMOX between 2004 and 2014. Among these patients, 63 also received ALKYs. MGMT promoter gene methylation was assessed via pyrosequencing in 42 patients. RESULTS: Patients received a median of 6 courses of GEMOX. Twenty-four (23%) had an objective response (OR). The median progression-free survival (PFS) and overall survival were 7.8 and 31.6 months, respectively. In the 63 patients treated with both ALKYs and GEMOX, the ORs (22% and 22%) and the PFSs (7.5 and 7.3 months) were similar. The response was concordant in 53% of the patients. Promoter gene methylation of MGMT was associated with better outcomes with ALKYs (P = .03 for OR and P = .04 for PFS) but not GEMOX. CONCLUSIONS: GEMOX is effective against NETs; its activity is comparable to that of ALKYs, and it is not influenced by the MGMT status. Our data suggest that GEMOX might be preferred for patients with unmethylated MGMT tumors. Cancer 2015;121:3435-43.
BACKGROUND: The alkylating agents (ALKYs) streptozotocin, dacarbazine, and temozolomide currently are the main drugs used in systemic chemotherapy for neuroendocrine tumors (NETs). The promising activity shown by gemcitabine and oxaliplatin (GEMOX) in previous studies prompted this study 1) to confirm the use of GEMOX in a larger population of NET patients, 2) to compare its efficacy with that of ALKYs, and 3) to explore whether the O(6) -methylguanine-DNA methyltransferase (MGMT) status could help in selecting the chemotherapy regimen. METHODS: One hundred four patients with metastatic NETs (37 pancreatic NETs, 33 gastrointestinal NETs, 23 bronchial NETs, and 11 NETs of other/unknown origin) were treated with GEMOX between 2004 and 2014. Among these patients, 63 also received ALKYs. MGMT promoter gene methylation was assessed via pyrosequencing in 42 patients. RESULTS:Patients received a median of 6 courses of GEMOX. Twenty-four (23%) had an objective response (OR). The median progression-free survival (PFS) and overall survival were 7.8 and 31.6 months, respectively. In the 63 patients treated with both ALKYs and GEMOX, the ORs (22% and 22%) and the PFSs (7.5 and 7.3 months) were similar. The response was concordant in 53% of the patients. Promoter gene methylation of MGMT was associated with better outcomes with ALKYs (P = .03 for OR and P = .04 for PFS) but not GEMOX. CONCLUSIONS:GEMOX is effective against NETs; its activity is comparable to that of ALKYs, and it is not influenced by the MGMT status. Our data suggest that GEMOX might be preferred for patients with unmethylated MGMT tumors. Cancer 2015;121:3435-43.
Authors: Rachel P Riechelmann; Rui F Weschenfelder; Frederico P Costa; Aline Chaves Andrade; Alessandro Bersch Osvaldt; Ana Rosa P Quidute; Allan Dos Santos; Ana Amélia O Hoff; Brenda Gumz; Carlos Buchpiguel; Bruno S Vilhena Pereira; Delmar Muniz Lourenço Junior; Duilio Reis da Rocha Filho; Eduardo Antunes Fonseca; Eduardo Linhares Riello Mello; Fabio Ferrari Makdissi; Fabio Luiz Waechter; Francisco Cesar Carnevale; George B Coura-Filho; Gustavo Andrade de Paulo; Gustavo Colagiovanni Girotto; João Evangelista Bezerra Neto; João Glasberg; Jose Claudio Casali-da-Rocha; Juliana Florinda M Rego; Luciana Rodrigues de Meirelles; Ludhmila Hajjar; Marcos Menezes; Marcello D Bronstein; Marcelo Tatit Sapienza; Maria Candida Barisson Villares Fragoso; Maria Adelaide Albergaria Pereira; Milton Barros; Nora Manoukian Forones; Paulo Cezar Galvão do Amaral; Raphael Salles Scortegagna de Medeiros; Raphael L C Araujo; Regis Otaviano França Bezerra; Renata D'Alpino Peixoto; Samuel Aguiar; Ulysses Ribeiro; Tulio Pfiffer; Paulo M Hoff; Anelisa K Coutinho Journal: Ecancermedicalscience Date: 2017-01-26
Authors: Alessandra Pulvirenti; Nitya Raj; Sara Cingarlini; Antonio Pea; Laura H Tang; Claudio Luchini; Joanne F Chou; Elisabetta Grego; Ioana Marinova; Marinela Capanu; Luca Landoni; Aldo Scarpa; Peter J Allen; David S Klimstra; Diane L Reidy-Lagunes Journal: Pancreas Date: 2021-02-01 Impact factor: 3.243