Pierpaolo Pastina1, Valerio Nardone1, Stefania Croci1, Giuseppe Battaglia1, Francesca Vanni1, Cristiana Bellan2, Marcella Barbarino2, Veronica Ricci3, Susan Costantini4, Francesca Capone4, Cirino Botta5, Mayra Rachele Zarone6, Gabriella Misso6, Mariarosaria Boccellino6, Michele Caraglia6,7, Antonio Giordano2,7, Piero Paladini8, Pierfrancesco Tassone5,7, Pierosandro Tagliaferri5, Maria Grazia Cusi9, Luigi Pirtoli1, Pierpaolo Correale1. 1. Radiotherapy Unit, Department of Medicine, Surgery, and Neuroscience, Siena University, Siena, Italy. 2. Pathology Unit, Department of Medicine, Surgery, and Neuroscience, Siena University, Siena, Italy. 3. Radiology Unit, Department of Medicine, Surgery, and Neuroscience, Siena University, Siena, Italy. 4. CROM, Istituto Nazionale Tumori "Fondazione G. Pascale", IRCCS, Napoli, Italy. 5. Department of Experimental and Clinical Medicine, Magna Graecia University, Salvatore Venuta University Campus, Catanzaro, Italy. 6. Department of Biochemistry, Biophysics and General Pathology, University of Campania "Luigi Vanvitelli", Naples, Italy. 7. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USA. 8. Unit of Thoracic Surgery, Department of Medicine, Surgery, and Neuroscience, Siena University, Siena, Italy. 9. Microbiology and Virology Unit, Department of Medical Biotechnology, Siena University, Siena, Italy.
Abstract
BACKGROUND: Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/- bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology. METHODS: Retrospective analysis was carried out in a subset of 31 patients with squamous histology enrolled in the study between September 2007 and September 2015. All of the patients received chemotherapy with cisplatin (30 mg/sqm, days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE) and 14 of them also received bevacizumab 5 mg/kg on the day 3q21 (mPEBev regimen). RESULTS: This treatment showed a disease control rate of 71% with a mean progression free survival (PFS) and overall survival (OS) of 13.6 and 17 months respectively. After 4 treatment courses, 6 patients showing a remarkable tumor shrinkage, underwent to radical surgery, attaining a significant advantage in term of survival (P=0.048). Kaplan-Meier and log-rank test identified the longest survival in patients presenting low baseline levels in neutrophil-to-lymphocyte ratio (NLR) (P=0.05), interleukin (IL) 17A (P=0.036), regulatory-T-cells (Tregs) (P=0.020), and activated CD83+ dendritic cells (DCs) (P=0.03). CONCLUSIONS: These results suggest that the mPE +/- bevacizumab regimen is feasible and should be tested in comparative trials in advanced squamous-NSCLC (sqNSCLC). Moreover, its immune-biological effects strongly suggest the investigation in sequential combinations with immune check-point inhibitors.
BACKGROUND: Results from the BEVA2007 trial, suggest that the metronomic chemotherapy regimen with dose-fractioned cisplatin and oral etoposide (mPE) +/- bevacizumab, a monoclonal antibody to the vascular endothelial growth factor (VEGF), shows anti-angiogenic and immunological effects and is a safe and active treatment for metastatic non-small cell lung cancer (mNSCLC) patients. We carried out a retrospective analysis aimed to evaluate the antitumor effects of this treatment in a subset of patients with squamous histology. METHODS: Retrospective analysis was carried out in a subset of 31 patients with squamous histology enrolled in the study between September 2007 and September 2015. All of the patients received chemotherapy with cisplatin (30 mg/sqm, days 1-3q21) and oral etoposide (50 mg, days 1-15q21) (mPE) and 14 of them also received bevacizumab 5 mg/kg on the day 3q21 (mPEBev regimen). RESULTS: This treatment showed a disease control rate of 71% with a mean progression free survival (PFS) and overall survival (OS) of 13.6 and 17 months respectively. After 4 treatment courses, 6 patients showing a remarkable tumor shrinkage, underwent to radical surgery, attaining a significant advantage in term of survival (P=0.048). Kaplan-Meier and log-rank test identified the longest survival in patients presenting low baseline levels in neutrophil-to-lymphocyte ratio (NLR) (P=0.05), interleukin (IL) 17A (P=0.036), regulatory-T-cells (Tregs) (P=0.020), and activated CD83+ dendritic cells (DCs) (P=0.03). CONCLUSIONS: These results suggest that the mPE +/- bevacizumab regimen is feasible and should be tested in comparative trials in advanced squamous-NSCLC (sqNSCLC). Moreover, its immune-biological effects strongly suggest the investigation in sequential combinations with immune check-point inhibitors.
Authors: Giorgio Vittorio Scagliotti; Purvish Parikh; Joachim von Pawel; Bonne Biesma; Johan Vansteenkiste; Christian Manegold; Piotr Serwatowski; Ulrich Gatzemeier; Raghunadharao Digumarti; Mauro Zukin; Jin S Lee; Anders Mellemgaard; Keunchil Park; Shehkar Patil; Janusz Rolski; Tuncay Goksel; Filippo de Marinis; Lorinda Simms; Katherine P Sugarman; David Gandara Journal: J Clin Oncol Date: 2008-05-27 Impact factor: 44.544
Authors: Lisa K Puntigam; Sandra S Jeske; Marlies Götz; Jochen Greiner; Simon Laban; Marie-Nicole Theodoraki; Johannes Doescher; Stephanie E Weissinger; Cornelia Brunner; Thomas K Hoffmann; Patrick J Schuler Journal: Int J Mol Sci Date: 2020-07-22 Impact factor: 5.923