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1. The organ-specific nitric oxide synthase activity in the interaction with sympathetic nerve activity: a hypothesis

Author

S Liskova

Subjects
medicine.medical_specialty, Sympathetic Nervous System, Nitric Oxide Synthase Type III, Physiology, Blood Pressure, Nitric Oxide Synthase Type I, 030204 cardiovascular system & hematology, Kidney, Nitric Oxide, Nitric oxide, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Enos, Internal medicine, medicine, Animals, Humans, Neurotransmitter, reproductive and urinary physiology, Denervation, biology, Brain, General Medicine, Rostral ventrolateral medulla, musculoskeletal system, medicine.disease, biology.organism_classification, body regions, Nitric oxide synthase, Endocrinology, nervous system, chemistry, Pathophysiology of hypertension, Hypertension, cardiovascular system, biology.protein, Minireview, Brainstem, 030217 neurology & neurosurgery
Abstract

The sympathetic nerve activity (SNA) is augmented in hypertension. SNA is regulated by neuronal nitric oxide synthase (nNOS) or endothelial nitric oxide synthase (eNOS) activity in hypothalamic paraventricular nuclei (PVN) and/or brainstem rostral ventrolateral medulla. High nNOS or eNOS activity within these brain regions lowers the SNA, whereas low cerebral nNOS and/or eNOS activity causes SNA augmentation. We hypothesize that the decreased cerebral nNOS/eNOS activity, which allows the enhancement of SNA, leads to the augmentation of renal eNOS/nNOS activity. Similarly, when the cerebral nNOS/eNOS activity is increased and SNA is suppressed, the renal eNOS/nNOS activity is suppressed as well. The activation of endothelial α2-adrenoceptors, may be a possible mechanism involved in the proposed regulation. Another possible mechanism might be based on nitric oxide, which acts as a neurotransmitter that tonically activates afferent renal nerves, leading to a decreased nNOS activity in PVN. Furthermore, the importance of the renal nNOS/eNOS activity during renal denervation is discussed. In conclusion, the presented hypothesis describes the dual organ-specific role of eNOS/nNOS activity in blood pressure regulation and suggests possible connection between cerebral NOS and renal NOS via activation or inhibition of SNA, which is an innovative idea in the concept of pathophysiology of hypertension.

Published
2021

2. Effect of iron oxide nanoparticles on vascular function and nitric oxide production in acute stress-exposed rats

Author

S Liskova, M Kluknavský, M Okuliarová, Peter Balis, M Škrátek, I. Sekaj, P Valovič, Angelika Puzserova, A Mičurová, J Maňka, and Iveta Bernatova

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Mean arterial pressure, Vascular smooth muscle, Physiology, Nitric Oxide, Rats, Inbred WKY, Nitric oxide, Excretion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Stress, Physiological, Hepcidin, Internal medicine, medicine, Animals, biology, Articles, General Medicine, Rats, Nitric oxide synthase, 030104 developmental biology, Endocrinology, chemistry, biology.protein, Magnetic Iron Oxide Nanoparticles, Endothelium, Vascular, Sodium nitroprusside, Nitric Oxide Synthase, 030217 neurology & neurosurgery, Acetylcholine, medicine.drug
Abstract

We investigated whether polyethylene glycol-coated Fe(3)O(4) nanoparticles (IONs), acute stress and their combination modifies vascular functions, nitric oxide synthase (NOS) activity, mean arterial pressure (MAP) as well as hepcidin and ferritin H gene expressions in Wistar-Kyoto rats. Rats were divided into control, ION-treated rats (1 mg Fe/kg i.v.), repeated acute air-jet stress-exposed rats and IONs-and-stress co-exposed rats. Maximal acetylcholine (ACh)-induced and sodium nitroprusside (SNP)-induced relaxations in the femoral arteries did not differ among the groups. IONs alone significantly elevated the Nω-nitro-L-arginine methyl ester (L-NAME)-sensitive component of ACh-induced relaxation and reduced the sensitivity of vascular smooth muscle cells to SNP. IONs alone also elevated NOS activity in the brainstem and hypothalamus, reduced NOS activity in the kidneys and had no effect in the liver. Acute stress alone failed to affect vascular function and NOS activities in all the tissues investigated but it elevated ferritin H expression in the liver. In the ION-and-stress group, NOS activity was elevated in the kidneys and liver, but reduced in the brainstem and hypothalamus vs. IONs alone. IONs also accentuated air-jet stress-induced MAP responses vs. stress alone. Interestingly, stress reduced ION-originated iron content in blood and liver while it was elevated in the kidneys. In conclusion, the results showed that 1) acute administration of IONs altered vascular function, increased L-NAME-sensitive component of ACh-induced relaxation and had tissue-dependent effects on NOS activity, 2) ION effects were considerably reduced by co-exposure to repeated acute stress, likely related to decrease of ION-originated iron in blood due to elevated decomposition and/or excretion.

Published
2020

3. Biopharmaceuticals safety perception in Slovakia: considerations and real-life pharmacovigilance data

Author

S Fundarkova, Tisonova J, S Liskova, Monika Laššánová, and S. Lassan

Subjects
Drug, Economics and Econometrics, medicine.medical_specialty, Slovakia, media_common.quotation_subject, Filgrastim, Pharmacovigilance, Drug control, Quality of life, Internal medicine, Materials Chemistry, Media Technology, medicine, Adverse Drug Reaction Reporting Systems, Humans, Biosimilar Pharmaceuticals, media_common, business.industry, Forestry, Biosimilar, medicine.disease, Infliximab, Quality of Life, Perception, business, Adverse drug reaction, medicine.drug
Abstract

Objectives Biopharmaceuticals improved the prognosis and quality of life of patients with chronic diseases. The aim of our study was to analyse the total reported suspected adverse drug reactions (ADR) and ADRs of reference biologicals and their biosimilars in Slovakia. Methods Using data from the State Institute for Drug Control database, we analysed the trends of suspected ADR submitted between 2001-2017 including the registered biosimilars and their reference biologicals: erythropoietin, filgrastim and infliximab. Results Severe suspected ADR represented 42.95 % from all the reported cases (n=13,462) over the time period 2006-2017 and 54.98 % over 2015-2017 respectively. Reports from 2015-2017 were further analysed. From 4,364 cases, 27 were associated with infliximab and one with erythropoietin. 75 % of these ADR were severe including one death. The difference between the suspected ADR for infliximab reference biological compared to the biosimilar was not statistically significant (p=0.171) after adjustment to the number of prescribed drug units. Conclusion We did not find any evidence of increased risks associated with biosimilars compared to reference biologics. The spontaneous reporting system represents an inexpensive tool of reporting ADRs and should be utilized more frequently by health professionals, but even more importantly, by patients (Tab. 3, Fig. 2, Ref. 30). Text in PDF www.elis.sk Keywords: adverse drug reaction, spontaneous reporting, biopharmaceuticals, biosimilars, infliximab.

Published
2021

4. Phase II Study of Everolimus (E) in Refractory Germ Cell Tumors (GCTS)

Author

Jana Obertova, Zuzana Sycova-Mila, Michal Mego, S Liskova, Daniela Svetlovska, Patrik Palacka, Viera Miskovska, M. Reckova, Rajec J, and Jozef Mardiak

Subjects
Cisplatin, Oncology, Chemotherapy, medicine.medical_specialty, Everolimus, biology, business.industry, medicine.medical_treatment, Phases of clinical research, Cancer, Hematology, medicine.disease, Regimen, Internal medicine, biology.protein, Medicine, PTEN, Germ cell tumors, business, medicine.drug
Abstract

Background GCTs represent a model for the cure of cancer. Nonetheless, a small proportion of patients (pts) develop disease recurrence. Loss of the tumor suppressor gene PTEN (phosphatase and tensin homolog) marks the transition from intratubular germ cell neoplasias (ITGCN) to invasive GCTs. PTEN inactivation is associated with dysregulation of PI3K/Akt pathway and increased mTOR signalling. We hypothesize that dysregulation of PI3K/Akt pathway due to PTEN inactivation in GCTs suggests that these pts would have greater benefit from mTOR inhibition. Methods In December 2011, National Cancer Institute of Slovakia launched a one arm, two-staged phase II study aimed to evaluate the efficacy and toxicity of Everolimus (E) in pts with refractory GCTs. The primary objective is to determine the efficacy of E in pts with refractory GCTs. The pts with radiological and/or serological proof of relapsed GCTs, who were not amenable to be cured by chemotherapy or surgery and who failed at least two platinum-based regimens or one platinum regimen in case of platinum-refractory disease or primary mediastinal non-seminomatous GCTs have been eligible. E has been administered at a dose of 10mg daily until progression or unacceptable toxicity. Results From December 2011, 4 patients have been enrolled. Median age of patients is 28 years. All patients were pretreated with at least 3 cisplatin-based therapy, three patients were absolute cisplatin refractory, progressed directly on cisplatin-based therapy. We observed no unexpected toxicity. One patient experienced pneumonitis grade 3, and dose reduction was needed. One patient progressed early, while three patients are still on treatment for 1 + , 3+ and 5+ months. Conclusion Our preliminary data suggests that, Everolimus is safe and well tolerated drug in patients with GCT. Efficacy data is warranted. Disclosure All authors have declared no conflicts of interest.

Published
2012

5. RANDOMIZED PHASE II STUDY OF FIRST-LINE EVEROLIMUS (EVE) + BEVACIZUMAB (BEV) VERSUS INTERFERON ALFA-2A (IFN) + BEV IN PATIENTS (PTS) WITH METASTATIC RENAL CELL CARCINOMA (MRCC): RECORD-2

Author

Rickard Sandin, Javier Diaz, David Smith, investigators, H. Pandha, A. Damato, M. Del Prete, M. Reckova, E. Korbenfeld, A. Seth, Cristina Suarez, P. Celiz, S. Liskova, R.K. Sahoo, A. Felici, A. Suder, Francesco Cognetti, P. Gronesova, G. Martignoni, M. Jebali, E. Fernández-Parra, C. Bokemeyer, Yingwei Peng, M.C. Sebastia, H. Mullot, Daniele Raggi, D. Urosa Velasco, Begoña Mellado, J. Chester, Corina Andresen, Sally Ellis, N. Nicolai, A. Omar, A. Ambavane, Georg A. Bjarnason, Frank Priou, A. Vieillefond, T. Wahlgren, U. Harmenberg, H. Nemeth, M. Rivoire, Guru Sonpavde, C. Binder, V. Prati, M. Witkowski, R. Delva, J.F. Rodríguez-Moreno, L. Stern, V. Calderero, O. Bauduceau, Andrea Viqueira, K. Kaiser, Maurizio Colecchia, M.P. López Martí, M.E. Lampron, J.T. Hartmann, D. Tunali, Reza Elaidi, V. Galvis, Z. Sycova-Mila, Veg Team, R. von Moos, Jose Carlos Benitez, Simon Chowdhury, H. Mergenthaler, F. Arpaci, S. Cascinu, G. Erdem, A. Comte, J.M. Sepulveda Sanchez, K. Slimane, Mustafa Benekli, Paul Nathan, S. Van Belle, B. Metzner, Hussein M. Khaled, Q. Wang, Denice D. Tsao-Wei, J. Jin, H. Cortes-Funes, N. Clottens, P. Wilson, G. Procopio, A.L. Gentile, L. Burattini, Robert E. Hawkins, R. Montironi, G.R. Pond, Viorel Jinga, B. Ceccaldi, Tanya B. Dorff, S. Lata, Sergio Bracarda, P. Palacka, N. Karadurmus, S. Tumolo, Mario Sznol, A. Guillot, H. Spliid, C. Kahl, Cora N. Sternberg, K. Nagyivanyi, N. Sarwar, G. Krekeler, G. Fischer, S. Le Moulec, Brian I. Rini, R. Casciano, Derek Raghavan, F. Mehmud, N.V. Jensen, Suleyman Buyukberber, J.P. Fusco, Kim Edmonds, C. Messina, H.G. Sayer, Sanjiv S. Agarwala, R.J. Jones, J. Ribeiro, T. Geldart, A. González del Alba, E. López Juarez, G. Mead, Ben Challacombe, I. Brindel, T. M-H, F. Lumachi, S.M. M. Basso, E.Q. Bergan, R. Morales-Barrera, J.L. Perez Gracia, P. Cislo, I. Victoria, B. Sarsık, M. Cakar, S. Lee, Marc Campayo, R. Roy, A. Necchi, M. Ozturk, Hai T. Tran, R. Mondéjar Solís, M. Schmidt, N. Dalal, J. Coombs, Danka Cholujova, Ashok Kumar Gupta, C. Poehlein, S. Ozkan, B. Maughan, W.E. Berdel, C. Masini, F. Pili, A. Vuillemin, R. Martínez-Monge, J.J. Zudaire, F. Orlandi, C. Cianci, J. Bay, J. Thompson, C. Theodore, L. McCann, Anne Gold, N. Muzaffar, A. Houlgatte, L. Bergmann, X. Ren, G.B. Chiara, M. Ktiouet, Muhammad A. Khattak, J. Eymard, N. Nagaraj, J. Yu, Alfredo Falcone, Oezlem Anak, C. Korn, Karim Fizazi, P. Biron, V. Usakova, E. Gökmen, A. Flechon, R.R. Prasad, R. Bianco, M.E. Zudaire, S.J. Park, U. De Giorgi, Brad Rosbrook, F. Selle, A. Zurita-Saavedra, E. Verzoni, Günter Niegisch, J.L. Álvarez-Ossorio, Börje Ljungberg, N. Lainez, T.M. Kim, Irina Proskorovsky, C. Rodriguez-Antona, L. Maute, Komel Khabra, F. Algaba, A.C. Palozzo, L. Bodnar, O. Etxaniz, L. Galli, J.-P. Lotz, S.S. Sridhar, Yongchel Ahn, G. El Hussiny, E. Paze, M. Bianconi, E. Esteban, I. Fernandes, Omid Hamid, V. Kruse, P.F. Geertsen, Laurence Albiges, Joseph C. Cappelleri, M. Gaulet, Mayer Fishman, W. Kong, Aslam Sohaib, L. Formisano, B. Biswas, Heui June Ahn, C. Nicolau, G. Ye, P. Beuzeboc, C. Arqueros, A. Bair, H. Abdel Azim, F. Riet, T. Turker, J. Fouque, John D. Powderly, G. Velasco, J. Areal, G. Papiani, B. Wittig, D.R. Siemens, U. Anido, G. Anguera, J. Medioni, K. Pennert, G.G. Hermann, Igor Puzanov, D. Herchenhorn, James Larkin, B. Bui, P. Srinivasan, I. Waxman, J. Garcia-Donas, M. Ermani, J. Malet, R. Buzzoni, C. Emmanouilides, L. Kumar, Xin-Yun Huang, J. Beaumont, M. Bragagni, F. Fabbri, M. Santoni, A. Castillo, A. Pantuck, S. Imbevaro, G. Chahine, K. Zhang, D. Ondrus, Parminder Singh, Francesco Massari, S. Spanik, Svetozar Gogov, J. Kowalski, N. Pardo, J.M. Miclea, Dae Ho Lee, P. Gerletti, P. Rocca Cossu, H.J. Choi, Stéphane Oudard, J. Guo, A. Berkenblit, Pablo Maroto, A.R. Jazeih, L. Hodge, D. Ye, Daniel Castellano, David Cella, I.G. Sullivan, Vsevolod Matveev, I. Temby, Gwenaelle Gravis, J. Khalil, R. Fougeray, M. Wheater, G. Di Lorenzo, P. Landsman-Blumberg, A.J. Birtle, S. Zanetta, M. Harza, Y. Su, A. Badran, A. Alcaraz, K. Wood, S. Weikert, D. Chen, M. Bonomi, B. Paño, E. Garanzini, L. Ciuffreda, Lisa Derosa, D.J. George, L. Cerbone, J-H Ahn, A.J. McPartlin, E. Barsoum, J. Droz, Antonin Levy, T. Brechenmacher, J. Kim, A. Ozet, S Songül Yalçin, P.A. Zucali, F. Brusa, L. Steelman, J.J. Sánchez, O.E. Carranza, I. Bodrogi, Alain Ravaud, E. Boleti, L. Santomé, I. Chaib, J.V. Heymach, B. Sanchez, E. Matczak, Ying Chen, E. Castanon Alvarez, C. Farfan, J-P. Machiels, J. P. Maroto, J.H. Hong, S. Babakulov, G. Elhussiny, D. Santeufemia, L. Chen, A. Shamseddine, Jacek Pinski, S. Stergiopoulos, J.L. Cuadra Urteaga, A. Boeckenhoff, Viktor Grünwald, P. Sandström, C. Ketchens, S. Rudman, L. Costa, I. Cañamares, Shaowen Qin, M.C. Lopez Lopez, Darrel P. Cohen, A. Cappetta, R. De Vivo, M.J. Méndez-Vidal, Georgia Kollia, U. Kube, K.M. Boucher, Tim O'Brien, Z. Küronya, A.M. Molina, Y.-N. Wong, C. Ferrario, A.M. Gianni, M.D. Michaelson, R. Salvioni, Walter M. Stadler, M. Taron, S. Sarker, B. Kopf, L. Wang, B. Lutiger, Jon M. Wigginton, C. Sacco, J. Shanks, Sarvendra Kumar, C. Buges, L. Wood, M. Domenech, Riccardo Giampieri, M.P. Trojniak, R. Sabbatini, N. Leonhartsberger, R. Lewis, L. Anton-Aparicio, A.J. Zurita Saavedra, Yohann Loriot, D. Giannarelli, M. Cichowicz, M. Aglietta, E. Horn, N. Bonnin, J. Wang, M. Nicodemo, A. Bamias, X. Xiao, M. Calderon, P. Giannatempo, K. Dykstra, Lisa Pickering, Patricia A. English, G. Rosti, J. Ma, G. Guderian, Jean Jacques Patard, Andrew G. Bushmakin, N. Siddqui, P. Sabin Domínguez, C. Chevreau, J. Carles, D. Muskett, I.F. Tannock, A. Scarpa, G. Deplanque, Emilio Bria, L. Védrine, C. Chen, H. Villavicencio, S. Pan, Bohuslav Melichar, J. Palou, W. Kozłowski, Michal Mego, E. Jones, H. Ozturk, J.A. Arranz Arija, A. Benedict, C. Helissey, R. González Beca, G. Kooiman, Yuan Liu, C. May, K. Bíró, E. Hall, S. Vazquez-Estevez, M. Morente, R. Rosa, Raika Durusoy, A. Caty, R. Keyser, A. Shablak, J.A. Williams, D. Burcoveanu, M. Tschaika, S. Navruzov, E. Weith, F. de Braud, R. Kockelbergh, Begoña Perez-Valderrama, A.V. Soerensen, J.A. Peña, Christophe Massard, A. Chandra, M. Staehler, L.E. Abella, W. Arafat, G. Fargues, A. Darwish, E. De Coene, H. Sun, C. Martin Lorente, Robin Wiltshire, Cyrus Chargari, A. Louveau, E. Aitini, L. van Bortel, A. Onofri, A.A. Patel, I. Chirivella Gonzalez, F. Villacampa, J. Rajec, D. Biasoni, C. Szczylik, J. Schmitz, U. Mueller, P.F. Conte, M. Carducci, G. Tapia Rico, Anne Schuckman, Xun Lin, I. Alemany, A. Farnesi, E. Arevalo, Meral Kurt, M.O. Giganti, C. Song, I.G. Schmidt-Wolf, J. Pan, M. De Fromont, M. Schmidinger, K. Das, M. Yaman, C. Teghom, C. Boni, I. Ozer-Stillman, F. Maines, B. Moya Ortega, T.B. Powles, S. Pusceddu, I. Barista, I. Duran, S. Cierniak, M.E. Gore, R. Rosell, Jamal Tarazi, E. Kurt, D. Svetlovska, G. Li, F. Gyergyay, W. Yin, C. Porta, I. Park, M. Smoter, G. Rottenberg, S. Crabb, M. Rizzo, G. Gravis-Mescam, A. Spencer-Shaw, David M. Berman, R. Janciauskiene, F. Pons Valladares, I. Testa, E. Bajetta, Olga Valota, M. Lazaro, B. Esteves, Mario Scartozzi, M. Catanzaro, M. Arzoz, David F. McDermott, E. Sevin, Charles G. Drake, L. Ye, Ugur Coskun, A. Lorch, D. Pelov, D. Xanthaki, L. Nappi, G. Lo Re, Giampaolo Tortora, L. Ruiz, Kolette D. Fly, P. Mendez, M. Johnson, M. Jakobsson, Y. Lin, Sinil Kim, J.Y. Yuan, I. Chiappino, I.A. Muazzam, Xudong Zhang, K.J. Park, Stéphane Culine, C. Papandreou, S. Hauser, B. Paolini, O. Fernandez, D. Kalanovic, L. León, C. De La Piedra, R. Iacovelli, S. Provent, P.D. Simmonds, Michele Milella, D. Jäger, K. Massopust, G. Miolo, J. Neves, D. Amadori, F.L. Lim, M. Ramos Vazquez, A. De Both, S. Ozaydin, O. Reig Torras, E. Villa, G. Mickisch, T. Nguyen, R. Stec, M. Schroff, Cristina Suarez Rodriguez, S. Rottey, Boris Alekseev, O. Rick, D. Condori, W.J. Mackillop, J. Gligorov, Christopher M. Booth, A. Fontana, A.S. Ataergin, L. Capdevila, J.-F. Martini, M. Jimenez, J. Loewy, Piotr Tomczak, J. Hu, K.L. Baker-Neblett, M. Pastorek, P. Rescigno, V. Miskovska, F. Atzori, Thomas Gauler, K. Fode, Ü.E. Bagriacik, D. Nosov, Y. Kim, P.C. Lara, Frede Donskov, Michael B. Atkins, L. Géczi, V. Lorusso, Kiruthikah Thillai, F. Zhou, A.M. Aparicio, B. González, Susan Groshen, M. Aieta, R. Cathomas, E. Calvo, A. Lopez, S. Hernando, D.S. Heo, F. Goldwasser, F. Boccardo, Carlos H. Barrios, V. Damiano, Toni K. Choueiri, L.N. Pandite, F.J. Afonso, Jonathan Shamash, Fiona C Thistlethwaite, G.R. Hudes, Mellar P. Davis, D. Macedo, A. Font, Joaquim Bellmunt, S. Lundstam, Ignacio Gil-Bazo, T. Eisen, J. Qiu, Siamak Daneshmand, David I. Quinn, Ashok Panneerselvam, S. De Placido, L. Jacobasch, M. Climent, Luca Faloppi, Petri Bono, B.K. Mohanti, F. Valduga, Y. Huang, M. Zemanova, M. Fehr, E. Biasco, A. Kaprin, T. Montella, Cristian Loretelli, O. Ekinci, S. S¸en, C. Bailly, Sylvie Negrier, L. Ozkan, Beata Korytowsky, T. de Revel, A. Somers, B. Escudier, Umut Demirci, K. Stauch, Helen Boyle, A. Jirillo, C. Kim, R.A. Figlin, N. Shi, Joseph K. T. Lee, A. Jouinot, G. Abdel Metaal, R. Marconcini, C. Dubot, A. Pinto, L. Crino, T.E. Hutson, Thomas Powles, J. Mardiak, D. Cesic, Sook Ryun Park, D. Kim, S. Cetintas, Subramanian Hariharan, Alessandro Bittoni, M. Cotreau, J. Donovan, J. Obertova, Robert J. Motzer, and T. Steiner

Subjects
medicine.medical_specialty, medicine.medical_treatment, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Prostate, Internal medicine, medicine, Stomatitis, Objective response, 030304 developmental biology, 0303 health sciences, Proteinuria, Genitourinary system, business.industry, Treatment options, Hematology, medicine.disease, Nephrectomy, 3. Good health, medicine.anatomical_structure, Oncology, Tolerability, 030220 oncology & carcinogenesis, medicine.symptom, business
Abstract

Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progression-free survival (PFS) per central review based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success). Results In EVE + BEV (n = 182) and IFN + BEV (n = 183) arms, median age was 60/60 years, 76/72% of pts were men, MSKCC risk was favourable/intermediate/poor in 36/57/7% and 36/57/7% of pts, and 43/46% of pts had >2 organs involved, respectively. For EVE + BEV and IFN + BEV, median treatment duration was 8.5/8.3 months, respectively; 23/26% of pts discontinued due to AEs. In EVE + BEV and IFN + BEV arms, median PFS by central review was 9.3/10.0 months (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P =0.485), respectively; probability of subsequent phase III success was 5.1%. Results of central and local PFS analysis were consistent. Objective response rate was 27/28% in EVE + BEV and IFN + BEV arms, respectively. Median overall survival (OS) was not reached in the EVE + BEV arm and was 25.9 months (95% CI: 21.1, 30.2) in the IFN + BEV arm. Most frequent AEs (%) were stomatitis (63), proteinuria (49), diarrhoea (39), hypertension (38), and epistaxis (35) in EVE + BEV arm and decreased appetite (45), fatigue (41), proteinuria (37), and pyrexia (35) in IFN + BEV arm. Conclusions In RECORD-2, PFS and tolerability were similar for first-line EVE + BEV and IFN + BEV. Final OS analysis will occur after 2-year follow-up. Disclosure A. Ravaud: Alain Ravaud is a member of global, European, and/or French boards on urological tumors for Pfizer, Novartis, GlaxoSmithKline, Bayer-Schering, and Dendreon, and has received institutional grant support from Pfizer, Novartis, and Roche. O. Anak: Ozlem Anak is an employee of Novartis Pharma AG. D. Pelov: Diana Pelov is an employee of Novartis Pharmaceuticals Corporation. A. Louveau: Anne-Laure Louveau is an employee of Novartis Pharma S.A.S. T. M-H: Tay M-H is a speaker for an advisory board for Novartis Pharmaceuticals Corporation. B. Melichar: Bohuslav Melichar has received honoraria from Novartis and Roche and served on an advisory board for Roche. All other authors have declared no conflicts of interest.

Published
2012

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