Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial.
作者： Pascal Hammel , Portales Fabienne , Laurent Mineur , Jean-Philippe Metges , Thierry Andre
DOI: 10.1016/J.EJCA.2019.10.020
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摘要: Abstract Purpose This Phase IIb (NCT02195180) open-label study evaluated erythrocyte-encapsulated asparaginase (eryaspase) in combination with chemotherapy second-line advanced pancreatic adenocarcinoma. Methods Eligible patients were randomized 2:1 to either eryaspase gemcitabine or mFOLFOX6 (eryaspase arm), alone (control arm). Co-primary endpoints overall survival (OS) and progression-free (PFS) low asparagine synthetase (ASNS) expression. Secondary included OS PFS the entire population. Results 141 arm, n = 95; control n = 46). Median ASNS expression 6.2 months (95% CI, 5.1–8.8) arm versus 4.9 (3.1–7.1) (HR, 0.63; 95% 0.39–1.01; P = 0.056) 2.0 1.8–3.4) 1.8 (1.4–3.8) 0.67; 0.40–1.12; P = 0.127), respectively. In population, median for 6.0 4.4 0.60; P = 0.008) and 1.6 0.56; 0.37–0.84; P = 0.005), The of was well tolerated. most frequent Grade 3/4 adverse events (n = 93) gamma-glutamyltransferase increase (16 [17.2%]), neutropenia (12 [12.9%]), physical health deterioration [12.9%]). Conclusion Eryaspase is associated improvements PFS, irrespective A III trial underway.
sci-hub.se 参考文章(17)
Inge M. Appel, Monique L. den Boer, Jules P. P. Meijerink, Anjo J. P. Veerman, Nathalie C. M. Reniers, Rob Pieters, Up-regulation of asparagine synthetase expression is not linked to the clinical response L-asparaginase in pediatric acute lymphoblastic leukemia. Blood. ,vol. 107, pp. 4244- 4249 ,(2006) , 10.1182/BLOOD-2005-06-2597
Jaekyoung Son, Costas A. Lyssiotis, Haoqiang Ying, Xiaoxu Wang, Sujun Hua, Matteo Ligorio, Rushika M. Perera, Cristina R. Ferrone, Edouard Mullarky, Ng Shyh-Chang, Ya’an Kang, Jason B. Fleming, Nabeel Bardeesy, John M. Asara, Marcia C. Haigis, Ronald A. DePinho, Lewis C. Cantley, Alec C. Kimmelman, Glutamine supports pancreatic cancer growth through a KRAS-regulated metabolic pathway Nature. ,vol. 496, pp. 101- 105 ,(2013) , 10.1038/NATURE12040
Abhinav Shrivastava, Abdul Arif Khan, Mohsin Khurshid, Mohd Abul Kalam, Sudhir K. Jain, Pradeep K. Singhal, Recent developments in L-asparaginase discovery and its potential as anticancer agent. Critical Reviews in Oncology Hematology. ,vol. 100, pp. 1- 10 ,(2016) , 10.1016/J.CRITREVONC.2015.01.002
Helen Dimitriou, Christianna Choulaki, Chryssoula Perdikogianni, Eftichia Stiakaki, Maria Kalmanti, Expression levels of ASNS in mesenchymal stromal cells in childhood acute lymphoblastic leukemia International Journal of Hematology. ,vol. 99, pp. 305- 310 ,(2014) , 10.1007/S12185-014-1509-Y
Nan Su, Yuan-Xiang Pan, Mi Zhou, Richard C. Harvey, Stephen P. Hunger, Michael S. Kilberg, Correlation between asparaginase sensitivity and asparagine synthetase protein content, but not mRNA, in acute lymphoblastic leukemia cell lines. Pediatric Blood & Cancer. ,vol. 50, pp. 274- 279 ,(2008) , 10.1002/PBC.21213
Thierry Conroy, Françoise Desseigne, Marc Ychou, Olivier Bouché, Rosine Guimbaud, Yves Bécouarn, Antoine Adenis, Jean-Luc Raoul, Sophie Gourgou-Bourgade, Christelle de la Fouchardière, Jaafar Bennouna, Jean-Baptiste Bachet, Faiza Khemissa-Akouz, Denis Péré-Vergé, Catherine Delbaldo, Eric Assenat, Bruno Chauffert, Pierre Michel, Christine Montoto-Grillot, Michel Ducreux, FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer The New England Journal of Medicine. ,vol. 364, pp. 1817- 1825 ,(2011) , 10.1056/NEJMOA1011923
Helmut Oettle, Hanno Riess, Jens M. Stieler, Gerhard Heil, Ingo Schwaner, Jörg Seraphin, Martin Görner, Matthias Mölle, Tim F. Greten, Volker Lakner, Sven Bischoff, Marianne Sinn, Bernd Dörken, Uwe Pelzer, Second-Line Oxaliplatin, Folinic Acid, and Fluorouracil Versus Folinic Acid and Fluorouracil Alone for Gemcitabine-Refractory Pancreatic Cancer: Outcomes From the CONKO-003 Trial Journal of Clinical Oncology. ,vol. 32, pp. 2423- 2429 ,(2014) , 10.1200/JCO.2013.53.6995
Daniel D Von Hoff, Thomas Ervin, Francis P Arena, E Gabriela Chiorean, Jeffrey Infante, Malcolm Moore, Thomas Seay, Sergei A Tjulandin, Wen Wee Ma, Mansoor N Saleh, Marion Harris, Michele Reni, Scot Dowden, Daniel Laheru, Nathan Bahary, Ramesh K Ramanathan, Josep Tabernero, Manuel Hidalgo, David Goldstein, Eric Van Cutsem, Xinyu Wei, Jose Iglesias, Markus F Renschler, None, Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine The New England Journal of Medicine. ,vol. 369, pp. 1691- 1703 ,(2013) , 10.1056/NEJMOA1304369
Hongyan Cui, Stephanie Darmanin, Mitsuteru Natsuisaka, Takeshi Kondo, Masahiro Asaka, Masanobu Shindoh, Fumihiro Higashino, Junji Hamuro, Futoshi Okada, Masataka Kobayashi, Koji Nakagawa, Hideyuki Koide, Masanobu Kobayashi, Enhanced Expression of Asparagine Synthetase under Glucose-Deprived Conditions Protects Pancreatic Cancer Cells from Apoptosis Induced by Glucose Deprivation and Cisplatin Cancer Research. ,vol. 67, pp. 3345- 3355 ,(2007) , 10.1158/0008-5472.CAN-06-2519
Andrea Wang-Gillam, Chung-Pin Li, György Bodoky, Andrew Dean, Yan-Shen Shan, Gayle Jameson, Teresa Macarulla, Kyung-Hun Lee, David Cunningham, Jean F Blanc, Richard A Hubner, Chang-Fang Chiu, Gilberto Schwartsmann, Jens T Siveke, Fadi Braiteh, Victor Moyo, Bruce Belanger, Navreet Dhindsa, Eliel Bayever, Daniel D Von Hoff, Li-Tzong Chen, Clarence Adoo, Thomas Anderson, Jamil Asselah, Alan Azambuja, Carolyn Bampton, Carlos Henrique Barrios, Tanios Bekaii-Saab, Melichar Bohuslav, David Chang, Jen-Shi Chen, Yeu-Chin Chen, Hye Jin Choi, Ik Joo Chung, Vincent Chung, Tibor Csoszi, Antonio Cubillo, Linda DeMarco, Maike de Wit, Tomislav Dragovich, William Edenfield, Luis Enrique Fein, Fábio Franke, Martin Fuchs, Vega Gonzales-Cruz, Alberto Gozza, Rivera Herrero Fernando, Rosario Iaffaioli, Jitka Jakesova, Zsuzsanna Kahan, Misagh Karimi, Jun Suk Kim, Ernesto Korbenfeld, Istvan Lang, Fa-Chyi Lee, Kuan-Der Lee, Lara Lipton, Wen Wee Ma, Laszlo Mangel, Raul Mena, Daniel Palmer, Shubham Pant, Joon Oh Park, Paolo Piacentini, Uwe Pelzer, Javier Gallego Plazas, Cooray Prasad, Kun-Ming Rau, Jean-Luc Raoul, Donald Richards, Paul Ross, Luis Schlittler, Martin Smakal, Vladimira Stahalova, Cora Sternberg, Thomas Seufferlein, Niall Tebbutt, Jeferson Jose Vinholes, Raymond Wadlow, Milkos Wenczl, Mark Wong, None, Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial The Lancet. ,vol. 387, pp. 545- 557 ,(2016) , 10.1016/S0140-6736(15)00986-1