27 results on '"Dito, E."'
Search Results
2. P2.02: Investigation of the Effects Induced on Endothelial Function by the Human T2238C Anp Gene Molecular Variant
- Author
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Rubattu, S., Sciarretta, S., Calvieri, C., Castello, L., Battistoni, A., De Giusti, M., Dito, E., Marra, A., Laurino, I., Pagliaro, B., and Volpe, M.
- Published
- 2011
- Full Text
- View/download PDF
3. 451 Correlative and updated clinical endpoint analysis of a multicenter phase II trial of selumetinib (AZD6244) plus erlotinib in chemotherapy-refractory advanced pancreatic adenocarcinoma (PDAC)
- Author
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Ko, A.H., primary, Tempero, A.H., additional, Bekaii-Saab, T.B., additional, Kuhn, P., additional, Courtin, R., additional, Ziyeh, S., additional, Tahiri, S., additional, Kelley, R.K., additional, Dito, E., additional, Ong, A., additional, Linetskaya, R., additional, Talasaz, A., additional, Venook, A.P., additional, and Korn, W., additional
- Published
- 2014
- Full Text
- View/download PDF
4. A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer
- Author
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Ko, A H, primary, Tempero, M A, additional, Shan, Y-S, additional, Su, W-C, additional, Lin, Y-L, additional, Dito, E, additional, Ong, A, additional, Wang, Y-W, additional, Yeh, C G, additional, and Chen, L-T, additional
- Published
- 2013
- Full Text
- View/download PDF
5. AMINO TERMINAL NATRIURETIC PEPTIDES AND ASSOCIATION TO GLOBAL CARDIOVASCULAR RISK IN A MALE ADULT POPULATION FROM SOUTHERN ITALY
- Author
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Barbato, A., primary, Sciarretta, S., additional, Marchitti, S., additional, Iacone, R., additional, Battistoni, A., additional, De Giusti, M., additional, Dito, E., additional, Marra, A., additional, Schiano di Cola, M., additional, Ippolito, R., additional, Calvieri, C., additional, Volpe, M., additional, Strazzullo, P., additional, and Rubattu, S., additional
- Published
- 2011
- Full Text
- View/download PDF
6. INVESTIGATION OF THE EFFECTS INDUCED ON ENDOTHELIAL FUNCTION BY THE HUMAN T2238C ANP GENE MOLECULAR VARIANT
- Author
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Rubattu, S., primary, Sciarretta, S., additional, Calvieri, C., additional, Castello, L., additional, Battistoni, A., additional, De Giusti, M., additional, Dito, E., additional, Marra, A., additional, Laurino, I., additional, Pagliaro, B., additional, and Volpe, M., additional
- Published
- 2011
- Full Text
- View/download PDF
7. A multinational phase II study of PEP02 (liposome irinotecan) for patients with gemcitabine-refractory metastatic pancreatic cancer.
- Author
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Ko, A. H., primary, Tempero, M. A., additional, Shan, Y., additional, Su, W., additional, Lin, Y., additional, Dito, E., additional, Ong, A., additional, Wang, Y., additional, Yeh, G., additional, and Chen, L., additional
- Published
- 2011
- Full Text
- View/download PDF
8. Biliary stent complications in clinical trials for advanced pancreatic cancer.
- Author
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Espinoza, A. M., primary, Ko, A. H., additional, Ostroff, J. W., additional, Venook, A. P., additional, Bergsland, E. K., additional, Kelley, R. K., additional, Dito, E., additional, Ong, A., additional, and Tempero, M. A., additional
- Published
- 2011
- Full Text
- View/download PDF
9. A multinational phase II study of liposome irinotecan (PEP02) for patients with gemcitabine-refractory metastatic pancreatic cancer.
- Author
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Ko, A. H., primary, Tempero, M. A., additional, Shan, Y., additional, Su, W., additional, Lin, Y., additional, Dito, E., additional, Ong, A., additional, Yeh, G., additional, and Chen, L., additional
- Published
- 2011
- Full Text
- View/download PDF
10. Abstracts
- Author
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Barthelemy, O., primary, Silvain, J., additional, Brieger, D., additional, Bellemain-Appaix, A., additional, Cayla, G., additional, Beygui, F., additional, Lancar, R., additional, Collet, J. P., additional, Mercadier, A., additional, Montalescot, G., additional, Cha, K. S., additional, Nam, Y. H., additional, Kim, J. H., additional, Park, S. Y., additional, Park, T. H., additional, Kim, M. H., additional, Kim, Y. D., additional, Lee, H. C., additional, Ahn, M. S., additional, Hong, T. J., additional, Blanco, R., additional, Blanco, F., additional, Szarfer, J., additional, Garcia Escudero, A., additional, Gigena, G., additional, Gagliardi, J., additional, Rodriguez, A., additional, Sarmiento, R., additional, Affatatto, S., additional, Riccitelli, M., additional, Petris, A., additional, Datcu, M. D., additional, Pop, C., additional, Radoi, M., additional, Arsenescu-Georgescu, C., additional, Petrescu, I., additional, Petrescu, L., additional, Serban, L., additional, Nechita, E., additional, Tatu-Chitoiu, G., additional, Dorobantu, M., additional, Benedek, I., additional, Craiu, E., additional, Sinescu, C., additional, Ionescu, D. D., additional, Ginghina, C., additional, Minescu, B., additional, Izzo, A., additional, Mantovani, P., additional, Tomasi, L., additional, Dall'oglio, L., additional, Bonatti, S., additional, Rosiello, R., additional, Romano, M., additional, Agostini, F., additional, Zanini, R., additional, Zhao, Z. Y., additional, Wu, Y. J., additional, Li, J. J., additional, Yany, Y. J., additional, Qian, H. Y., additional, Tang, Y. D., additional, Timoteo, A. T., additional, Toste, A., additional, Lousinha, A., additional, Ramos, R., additional, Oliveira, J. A., additional, Ferreira, M. L., additional, Ferreira, R. C., additional, Cabades, C., additional, Diez Gil, J. L., additional, Aguar, P., additional, Sanmiguel, D., additional, Lopez-March, A., additional, Marmol, R., additional, Guerra, L., additional, Girbes, V., additional, Ferrando, J., additional, Rincon De Arellano, A., additional, Patricio, L., additional, Blondal, M., additional, Ainla, T., additional, Marandi, T., additional, Eha, J., additional, Oliveira, M. M., additional, Silva, M. N., additional, Cunha, P. S., additional, Feliciano, J., additional, Silva, S., additional, Kanovsky, J., additional, Kala, P., additional, Parenica, J., additional, Poloczek, M., additional, Prymusova, K., additional, Kubkova, L., additional, Spinar, J., additional, Olinic, D., additional, Homorodean, C., additional, Ober, M., additional, Olinic, M., additional, Andrioaia, C., additional, Condac, A., additional, Masmoudi, M., additional, Berdaoui, B., additional, Labidi, S., additional, Tapia Ballesteros, C., additional, Hernandez Luis, C., additional, Sandin, M. G., additional, Vegas, J. M., additional, Andion, R., additional, Martinez, N., additional, Gonzalez, I. A., additional, Alvarado, M., additional, Amat, I. J., additional, San Roman, J. A., additional, Garcia Gonzalez, M. J., additional, Arroyo Ucar, E., additional, Hernandez Garcia, C., additional, Dorta Martin, M., additional, Marrero Rodriguez, F., additional, Dragu, R., additional, Kapeliovich, M., additional, Hammerman, H., additional, Silva, D., additional, Cortez-Dias, N., additional, Jorge, C., additional, Silva Marques, J., additional, Carilho Ferreira, P., additional, Robalo Martins, S., additional, Almeida Ribeiro, M., additional, Calisto, C., additional, Fiuza, M., additional, Lopes, M. G., additional, Milicevic, P., additional, Panic, M., additional, Stankovic, I., additional, Milicevic, D., additional, Kalezic, T., additional, Kafedzic, S., additional, Ilic, I., additional, Cerovic, M., additional, Putnikovic, B., additional, Neskovic, A., additional, Rott, D., additional, Leibowitz, D., additional, Monhart, Z., additional, Reissigova, J., additional, Grunfeldova, H., additional, Jansky, P., additional, Valente, B., additional, Villanueva Benito, I., additional, Solla, I., additional, Paredes, E., additional, Diaz Castro, O., additional, Calvo, F., additional, Baz, J. A., additional, Iniguez, A., additional, Aleksova, A., additional, Gerloni, R., additional, Belfiore, R., additional, Carriere, C., additional, Barbati, G., additional, Fabris, E., additional, Possa, F., additional, Nait, D., additional, Milo, M., additional, Sinagra, G., additional, Marques, N., additional, Mimoso, J., additional, Gomes, V., additional, Agra Bermejo, R. M., additional, Emad Abu Assi, E. A. A., additional, Sergio Raposeiras Roubin, S. R. R., additional, Pilar Cabanas Grandio, P. C. G., additional, Carlos Pena Gil, C. P. G., additional, Jose Maria Garcia Acuna, J. M. G. A., additional, Jose Ramon Gonzalez Juanatey, J. R. G. J., additional, Daly, M. J., additional, Scott, P., additional, Owens, C. G., additional, Tomlin, A., additional, Smith, B., additional, Adgey, A. A. J., additional, Alvarez-Contreras, L. R., additional, Juarez, U., additional, Altamirano, A., additional, Arias, A., additional, Alvarez-San Gabriel, A., additional, Gonzalez-Pacheco, H., additional, Martinez-Sanchez, C., additional, Rahnavardi, M., additional, Keshtkar-Jahromi, M., additional, Vakili, H., additional, Gholamin, S., additional, Razavi, S. M., additional, Gilis-Januszewski, T., additional, Mellwig, K.- P., additional, Wiemer, M., additional, Gilis-Januszewski, J., additional, Peterschroeder, A., additional, Koerfer, J., additional, Horstkotte, D., additional, Vrsalovic, M., additional, Getaldic, B., additional, Vrkic, N., additional, Pintaric, H., additional, Khan, S., additional, Wasan, B., additional, Moretti, L., additional, Grossi, P., additional, Silenzi, S., additional, Testa, M., additional, Candelori, L., additional, Clementi, L. N., additional, Forlini, M., additional, Lando, L., additional, Pezzuoli, M. L., additional, Corradetti, P., additional, Leurent, G., additional, Pennec, P. Y., additional, Filippi, E., additional, Moquet, B., additional, Hacot, J. P., additional, Druelles, P., additional, Rialan, A., additional, Rouault, G., additional, Coudert, I., additional, Le Breton, H., additional, Gevaert, S., additional, Tromp, F., additional, Vandecasteele, E., additional, De Somer, F., additional, Van Belleghem, Y., additional, Bouchez, S., additional, Martens, F., additional, Herck, I., additional, De Pauw, M., additional, Ludka, O., additional, Sepsi, M., additional, Miklik, R., additional, Dusek, L., additional, Tomcikova, D., additional, Garcia-Acuna, J. M., additional, Aguiar-Souto, P., additional, Raposeiras Roubin, S., additional, Agra-Bermejo, R., additional, Jacquet, M., additional, Abu-Assi, E., additional, Gonzalez-Juanatey, J. R., additional, Ibatov, A., additional, Labrova, R., additional, Karlik, R., additional, Lokaj, P., additional, She, Q., additional, Deng, S. B., additional, Huang, S. H., additional, Gu, L. J., additional, Rong, J. I. A. N., additional, Wu, Z. K., additional, Li, Y., additional, Zhang, J., additional, Parascan, L., additional, Campanile, A., additional, Spinelli, L., additional, Santulli, G., additional, Ciccarelli, M., additional, De Gennaro, S., additional, Assante Di Panzillo, E., additional, Trimarco, B., additional, Iaccarino, G., additional, Bobescu, E., additional, Datcu, G., additional, Dobreanu, D., additional, Doka, B., additional, Charniot, J.- C., additional, Cosson, C., additional, Albertini, J. P., additional, Bittar, R., additional, Giral, P., additional, Cherfils, C., additional, Guillerm, E., additional, Bonnefont-Rousselot, D., additional, Rusali, A., additional, Cojocaru, L., additional, Parepa, I., additional, Koizumi, T., additional, Iida, S., additional, Sato, J., additional, Kikutani, T., additional, Muramatsu, T., additional, Nishimura, S., additional, Komiyama, N., additional, Lee, W. P., additional, Ong, B. B., additional, Haralambos, K., additional, Townsend, D., additional, Rees, J. A. E., additional, Williams, E. J., additional, Halcox, J. P., additional, Mcdowell, I., additional, Damjanovic, M., additional, Koracevic, G., additional, Djordjevic-Radojkovic, D., additional, Pavlovic, M., additional, Krstic, N., additional, Ciric-Zdravkovic, S., additional, Stojkovic, A., additional, Perisic, Z., additional, Apostolovic, S., additional, Faustino, A., additional, Seca, L., additional, Barra, S., additional, Caetano, F., additional, Providencia, R., additional, Silva, J., additional, Gomes, P., additional, Costa, G., additional, Costa, M., additional, Leitao-Marques, A., additional, Volkova, A. L., additional, Arutyunov, G. P., additional, Bylova, N. A., additional, Dayter, I. I., additional, Jao, Y. T. F. N., additional, Fang, C. C., additional, Chen, Y., additional, Yu, C. L., additional, Wang, S. P., additional, Valencia, J., additional, Perez-Berbel, P., additional, Ruiz-Nodar, J. M., additional, Pineda, J., additional, Bordes, P., additional, Quintanilla, M., additional, Mainar, V., additional, Sogorb, F., additional, Santos, N., additional, Serrao, M., additional, Cafe, H., additional, Silva, B., additional, Oliveira, R., additional, Caires, G., additional, Drumond, A., additional, Araujo, J., additional, Providencia, R. A., additional, Gomes, P. L., additional, Pais, J. R., additional, Mota, P., additional, Leitao-Marques, A. M., additional, Farhan, S., additional, Jarai, R., additional, Tentzeris, I., additional, Vogel, B., additional, Freynhofer, M. K., additional, Wojta, J., additional, Huber, K., additional, Poli, M., additional, Trambaiolo, P., additional, Corsi, F., additional, De Luca, M., additional, Mustilli, M., additional, Lukic, V., additional, Simonetti, M., additional, Ferraiuolo, G., additional, Lettino, M., additional, Casella, G., additional, Conte, M. R., additional, De Luca, L., additional, Geraci, G., additional, Ceravolo, R., additional, Pani, A., additional, Fradella, G., additional, Schratter, A., additional, Thiele, H., additional, Klemm, T., additional, Demmin, K., additional, Lehmann, D., additional, Mende, M., additional, Schuler, G., additional, Pittl, U., additional, Chernova, A., additional, Nikulina, S. U., additional, Naruke, T., additional, Inomata, T., additional, Yanagisawa, T., additional, Maekawa, E., additional, Mizutani, T., additional, Shinagawa, H., additional, Nishii, M., additional, Takeuchi, I., additional, Takehana, H., additional, Izumi, T., additional, Paulo, C., additional, Mascarenhas, J., additional, Patacho, M., additional, Pimenta, J., additional, Bettencourt, P., additional, Nardai, S., additional, Szabo, G. Y., additional, Berta, B., additional, Edes, I., additional, Merkely, B., additional, Delgado Silva, J., additional, Baptista, R., additional, Faria, R., additional, Trigo, J., additional, Gago, P., additional, Gheorghe, G., additional, Nanea, I. T., additional, Cristea, A., additional, Almarichi, S., additional, Martins, H., additional, Saraiva, F., additional, Jorge, E., additional, Mendes, P. L., additional, Monteiro, P., additional, Costa, S., additional, Franco, F., additional, Providencia, L. A., additional, Nanea, T., additional, Gheorghe, G. S., additional, Visan, S., additional, Paun, N., additional, Gaber, R., additional, Delewi, R., additional, Nijveldt, R., additional, De Bruin, H. A., additional, Hirsch, A., additional, Van Der Laan, A., additional, Bouma, B. J., additional, Tijssen, J. P. G., additional, Van Rossum, A. C., additional, Zijlstra, F., additional, Piek, J. J., additional, Rus, H., additional, Donea, M., additional, Ciurea, C., additional, Ifteni, G., additional, Casolo, G., additional, Chioccioli, M., additional, Magnacca, M., additional, Del Meglio, J., additional, Comella, A., additional, Baratto, M., additional, Lera, J., additional, Salvadori, L., additional, Tessa, C., additional, Vignali, C., additional, Keca, Z., additional, Momcilov Popin, T., additional, Panic, G., additional, White, R., additional, Mateen, F., additional, Weaver, A., additional, Agmon, Y., additional, Okisheva, E., additional, Tsaregorodtsev, D., additional, Sulimov, V., additional, Amat Santos, I. J., additional, Hernandez, C., additional, Tapia, C., additional, Campo, A., additional, Fredman, D., additional, Svensson, L., additional, Rosenqvist, M., additional, Tadel-Kocjancic, S., additional, Radsel, P., additional, Knafelj, R., additional, Gorjup, V., additional, Noc, M., additional, Zima, E., additional, Jenei, Z. S., additional, Kovacs, E., additional, Osztheimer, I., additional, Molnar, L., additional, Horvath, A., additional, Becker, D., additional, Geller, L., additional, Maggi, R., additional, Furukawa, T., additional, Viscardi, V., additional, Brignole, M., additional, Leal, S. R. N., additional, Dores, H., additional, Rosario, I., additional, Monge, J., additional, Carvalho, M. J., additional, Arroja, I., additional, Leitao, A., additional, Fonseca, C., additional, Aleixo, A., additional, Silva, A., additional, Keuleers, S., additional, Herijgers, P., additional, Herregods, M. C., additional, Budts, W., additional, Dubois, C., additional, Meuris, B., additional, Verhamme, P., additional, Flameng, W., additional, Van De Werf, F., additional, Adriaenssens, T., additional, Badran, H., additional, Elnoamany, M., additional, Lolah, T., additional, Olariu, C., additional, Macarie, C., additional, Mollik, M. A. H., additional, Hassan, A. I., additional, Paul, T. K., additional, Haque, M. Z., additional, Jahan, R., additional, Rahmatullah, M., additional, Khatun, M. A., additional, Rahman, M. T., additional, Chowdhury, M. H., additional, Bustamante Munguira, J., additional, Tamayo, E., additional, Garcia-Cuenca, I., additional, Bustamante, E., additional, Gualis, J., additional, Gomez-Martinez, M. L., additional, Florez, S., additional, Gomez-Herreras, J. I., additional, Ramirez Rodriguez, R., additional, Ramirez Rodriguez, A. M., additional, Garcia-Bello, M. A., additional, Hernadez Ortega, E., additional, Caballero Dorta, E., additional, Garcia Quintana, A., additional, Piro Mastraccio, V., additional, Medina Fernandez Aceytuno, A., additional, Assanelli, E., additional, De Metrio, M., additional, Rubino, M., additional, Lauri, G., additional, Cabiati, A., additional, Campodonico, J., additional, Grazi, M., additional, Moltrasio, M., additional, Marana, I., additional, Marenzi, G., additional, Lovlien, M., additional, Schei, B., additional, Picon-Heras, R., additional, Acebal, C., additional, Garcia Rubira, J. C., additional, Vivas Balcones, D., additional, Nunez-Gil, I., additional, Ruiz-Mateos, B., additional, Ibanez, B., additional, Fernandez-Ortiz, A., additional, Vintila, V. D., additional, Enescu, O. A., additional, Stoicescu, C. I., additional, Udroiu, C., additional, Cinteza, M., additional, Tatu - Chitoiu, G., additional, Vinereanu, D., additional, Fresco, C., additional, De Biasio, M., additional, Muser, D., additional, Sappa, R., additional, Morocutti, G., additional, Bernardi, G., additional, Proclemer, A., additional, Fontanella, B., additional, Affatato, A., additional, Ciccarese, C., additional, Sacchini, M., additional, Volpini, M., additional, Bianchetti, F., additional, Verzura, G., additional, Dei Cas, L., additional, Pudil, R., additional, Blaha, V., additional, Vojacek, J., additional, Paraskevaidis, I., additional, Ikonomidis, I., additional, Parissis, J., additional, Papadopoulos, C., additional, Stasinos, V., additional, Bistola, V., additional, Anastasiou-Nana, M., additional, Shochat, M., additional, Shotan, A., additional, Kazatsker, M., additional, Gurovich, V., additional, Asif, A., additional, Noiman, E., additional, Levy, Y., additional, Blondhaim, D., additional, Rabinovich, P., additional, Meisel, S., additional, Petrovic, S., additional, Glasnovic, J., additional, Tomasevic, M., additional, Sakac, D., additional, Obradovic, S., additional, Londono Sanchez, O., additional, Pacreu, S., additional, Torres, L., additional, Mihaylov, G., additional, Shaban, G. M., additional, Trendafilova, E., additional, Krasteva, V., additional, Mudrov, T. S., additional, Didon, J. P., additional, Panageas, V., additional, Vlachos, N., additional, Pernat, A., additional, Radan, I., additional, Mozina, H., additional, Pepi, P., additional, Cionini, F., additional, Baccaglioni, N., additional, Viertel, A., additional, Havers, J., additional, Ballard, G., additional, Groenefeld, G., additional, Branco, L. M., additional, Ferreira, L., additional, Fiarresga, A., additional, Lettieri, L., additional, Reggiani, A., additional, Juarez Prera, R., additional, Blanco Palacios, G., additional, Martin, A.- C., additional, Manzo Silberman, S., additional, Chaib, A., additional, Varenne, O., additional, Allouch, P., additional, Salengro, E., additional, Jegou, A., additional, Margot, O., additional, Spaulding, C., additional, Diego, A., additional, De Miguel, A., additional, Cuellas, C., additional, Fraile, E., additional, Martin, J., additional, Vega, B., additional, Bangueses, R., additional, Fernandez-Vazquez, F., additional, Perez De Prado, A., additional, Leal, S., additional, Correia, M. J., additional, Monge, J. C., additional, Abecasis, J., additional, Garcia-Garcia, C., additional, Subirana, I., additional, Sala, J., additional, Bruguera, J., additional, Valle, V., additional, Sanz, G., additional, Fiol, M., additional, Aros, F., additional, Marrugat, J., additional, Elosua, R., additional, Barra, S. N. C., additional, Leitao Marques, A., additional, Yang, Y. J., additional, Xu, B., additional, Song, G. Y., additional, G, R. L., additional, Aleksic, A., additional, Serpytis, P., additional, Rucinskas, K., additional, Kalinauskas, A., additional, Karvelyte, N., additional, Santos De Sousa, C. I., additional, Ferreira, S., additional, Calaca, J., additional, Lousada, N., additional, Palma Reis, R., additional, Gualandro, D. M., additional, Seguro, L. F. B. C., additional, Braga, F. G. M., additional, Silvestre, O. M., additional, Lage, R. L., additional, Fabri, J., additional, Oliveira, M. T., additional, Urbano Moral, J. A., additional, Torres Llergo, J., additional, Solanilla Rodriguez, R., additional, Sanchez Gonzalez, A., additional, Martinez Martinez, A., additional, Den Uil, C. A., additional, Lagrand, W. K., additional, Van Der Ent, M., additional, Jewbali, L. S. D., additional, Cheng, J. M., additional, Spronk, P. E., additional, Simoons, M. L., additional, Mornos, C., additional, Dragulescu, D., additional, Ionac, A., additional, Guardado, J., additional, Azevedo, O., additional, Fernandes, M., additional, Canario-Almeida, F., additional, Sanfins, V., additional, Pereira, A., additional, Almeida, J., additional, Kaplunova, V. U., additional, Belenkov, Y. N., additional, Privalova, E. V., additional, Fomin, A. A., additional, Suvorov, A. Y., additional, Goodkova, A., additional, Rubakova, M. G., additional, Kuznetsova, I. A., additional, Semernin, E. N., additional, Keshavarzi, F., additional, Kojuri, J., additional, Mikhailov, V. M., additional, Vezhenkova, I. V., additional, Goodkova, A. Y. A., additional, Pavlovic, I., additional, Schwarz, M., additional, Jakl, G., additional, Smetana, P., additional, Perkmann, T., additional, Mayr, A., additional, Mair, J., additional, Klug, G., additional, Schocke, M., additional, Trieb, T., additional, Jaschke, W., additional, Pachinger, O., additional, Metzler, B., additional, Bronze Carvalho, L., additional, Azevedo, J., additional, Andrade, M. L., additional, Relvas, M. J., additional, Coucello, J., additional, Morais, G., additional, Seabra, M., additional, Afamefule, F., additional, Luaces Mendez, M., additional, Teijeiro-Mestre, R., additional, Nunez-Gil, I. J., additional, Leco-Gil, N., additional, Madronal-Cerezo, E., additional, Zannin, I., additional, Ruiz, J., additional, Orynchak, M. A., additional, Vakalyuk, I. I., additional, Vakalyuk, I. P., additional, Berezin, A., additional, Panasenko, T., additional, Cavusoglu, Y., additional, Cavusoglu, A., additional, Unluoglu, I., additional, Tek, M., additional, Demirustu, C., additional, Gorenek, B., additional, Unalacak, M., additional, Birdane, A., additional, Yuksel, F., additional, Ata, N., additional, Halcox, J. P. J., additional, Beyaztas, A., additional, Entok, E., additional, Uslu, I., additional, Schaefer, A., additional, Flierl, U., additional, Seydelmann, N., additional, Bauersachs, J., additional, Calmac, L., additional, Marinescu, S., additional, Tatu Chitoiu, G., additional, Fruntelata, A. G., additional, Hamdi, S., additional, Maazoun, Y., additional, Neji, A., additional, Farhat, O., additional, Majdoub, M., additional, Ben Hamda, K., additional, Maatouk, F., additional, Balanescu, S. M., additional, Nedelciuc, I., additional, Deleanu, D., additional, Ortan, F., additional, Mot, S., additional, Sinnaeve, P. R., additional, Moreels, S., additional, Coosemans, M., additional, Vydt, T., additional, Desmet, W., additional, Tobing, D., additional, Rifnaldi, R., additional, Juzar, D., additional, Firdaus, I., additional, Dharma, S., additional, Irmalita, I., additional, Kalim, H., additional, Bejiqi, R., additional, Retkoceri, R., additional, Bejiqi, H., additional, Kryeziu, L., additional, Kelmendi, M., additional, Borovci, S. H., additional, Victor, S. M., additional, Gnanaraj, A., additional, Deshmukh, R., additional, Mullasari, A. S., additional, Yahalom, M., additional, Kaiyal, R. S., additional, Roguin, N., additional, Bornstein, J., additional, Atar, S., additional, Farah, R., additional, Seca, L. F., additional, Leitao Marques, A. M., additional, Margato, R., additional, Sousa, P., additional, Ribeiro, H., additional, Rocha, L., additional, Correia, A., additional, Moreira, J. I., additional, Carvalho, H. 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M., additional, Dito, E., additional, De Giusti, M., additional, Lallo, A., additional, Fusco, D., additional, Davoli, M., additional, Volpe, M., additional, Autore, C., additional, Gamra, H., additional, Dridi, Z., additional, Hassine, M., additional, Addad, F., additional, Gherissi, I., additional, Reda, A., additional, Mahjoub, M., additional, Bouraoui, S., additional, Abdennadher, M., additional, Betbout, F., additional, Mota, P. M. F. P., additional, Silva, J. D., additional, Jankovic Tomasevic, R., additional, Djordjevic, V., additional, Djordjevic Radojkovic, D., additional, Scafa Udriste, A., additional, Fruntelata, A., additional, Gainoiu, E., additional, Bogdan, S., additional, Zamfir, D., additional, Teodorescu, C., additional, Guran, M., additional, Constantinescu, D., additional, Konopka, A., additional, Banaszewski, M., additional, Wojtkowska, I., additional, Stepinska, J., additional, Vidergold, J. V., additional, Osipova, I. V., additional, Tavrovskaya, T. V., additional, Galkina, J. V., additional, Timofeev, A. V., additional, Vorobyov, R. I., additional, Vorobyova, E. N., additional, Matos, L., additional, Carvalho, A. C. C., additional, Oliveira, W., additional, Cintra, F., additional, Poyares, D., additional, Andersen, M., additional, Martins, R., additional, Tufik, S., additional, Ostadal, P., additional, Brada, J., additional, Horakova, S., additional, Mlcek, M., additional, Hrachovina, V., additional, Kittnar, O., additional, Gorudko, I. V., additional, Buko, I. V., additional, Cherenkevich, S. N., additional, Polonetsky, L. Z., additional, Plotkin, V. Y., additional, Timoshina, M. A., additional, Azanchevskaya, S. V., additional, Chromov-Borisov, N. N., additional, Vorlat, A., additional, Snoep, L., additional, Claeys, M. J., additional, Vrints, C. J., additional, Palazzuoli, A., additional, Caputo, M., additional, Quatrini, I., additional, Calabro, A., additional, Antonelli, G., additional, Campagna, M. 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G., additional, Zatarain Nicolas, E., additional, Martinez Uruena, N., additional, Alvarado Montes De Oca, M., additional, Dytrych, V., additional, Kovarnik, T., additional, Smid, O., additional, Kral, A., additional, Aroutunov, A. G., additional, Intwala, S., additional, Jegere, I., additional, Shaalan, H. S. H., additional, Pagava, Z., additional, Agladze, R., additional, Shakarishvili, R., additional, Sharashidze, N., additional, Gujejiani, L., additional, Saatashvili, G., additional, Katova, T. 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A., additional, Adgey, J. A. A., additional, Caeiro Pereira, D., additional, Braga, P., additional, Fontes Carvalho, R., additional, Rodrigues, A., additional, Goncalves, M., additional, Simoes, L., additional, and Borisov, K. V., additional
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- 2010
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11. A phase II study of bevacizumab (BEV) plus erlotinib (ERL) in patients with gemcitabine (GEM)-refractory metastatic pancreatic cancer (MPC)
- Author
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Ko, A. H., primary, Dito, E., additional, Schillinger, B., additional, Venook, A. P., additional, Bergsland, E. K., additional, Korn, W. M., additional, and Tempero, M. A., additional
- Published
- 2008
- Full Text
- View/download PDF
12. A phase II study of gemcitabine (GEM) given at fixed-dose rate (FDR) infusion, low-dose cisplatin (CDDP), and bevacizumab (BEV) for metastatic adenocarcinoma of the pancreas (PanCa): Update with completion of study accrual
- Author
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Ko, A. H., primary, Dito, E., additional, Schillinger, B., additional, Venook, A. P., additional, Bergsland, E. K., additional, Wong, D., additional, Allen, J., additional, and Tempero, M. A., additional
- Published
- 2007
- Full Text
- View/download PDF
13. A phase II study of gemcitabine (GEM) given at fixed-dose rate (FDR) infusion, low-dose cisplatin (CDDP), and bevacizumab in metastatic pancreatic cancer (PanCa)
- Author
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Ko, A. H., primary, Dito, E., additional, Schillinger, B., additional, Hajnal, R., additional, Venook, A. P., additional, Bergsland, E. K., additional, Allen, J., additional, Rajpal, S., additional, and Tempero, M. A., additional
- Published
- 2006
- Full Text
- View/download PDF
14. A phase II study of fixed-dose rate (FDR) gemcitabine plus cisplatin for metastatic pancreatic adenocarcinoma (PanCa)
- Author
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Ko, A. H., primary, Dito, E., additional, Schillinger, B., additional, Venook, A. P., additional, Bergsland, E. K., additional, Allen, J., additional, and Tempero, M. A., additional
- Published
- 2004
- Full Text
- View/download PDF
15. Investigation of the effects induced on endothelial function by the human T2238C ANP gene molecular variant.
- Author
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Rubattu, S., Sciarretta, S., Calvieri, C., Castello, L., Battistoni, A., De Giusti, M., Dito, E., Marra, A., Laurino, I., Pagliaro, B., and Volpe, M.
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- 2011
- Full Text
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16. Sacubitril/valsartan: preliminary experience in post-acute stabilized patients with reduced ejection fraction heart failure.
- Author
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Parisi C, De Giusti M, Castello L, Dito E, Proietti F, and Tomai F
- Subjects
- Aged, Biphenyl Compounds, Drug Combinations, Female, Heart Failure physiopathology, Humans, Male, Middle Aged, Valsartan, Aminobutyrates therapeutic use, Angiotensin Receptor Antagonists therapeutic use, Heart Failure drug therapy, Stroke Volume physiology, Tetrazoles therapeutic use
- Abstract
Introduction: We investigated the effectiveness of sacubitril/valsartan by performing laboratory tests and a 6-minute walking test (6-MWT) at 1 and 6 months after treatment initiation., Methods: We evaluated patients admitted to our Cardiology Department, stabilized after an episode of acute decompensated heart failure (HF), who were considered eligible for sacubitril/valsartan therapy. Therapy was initiated after interrupting angiotensin-converting enzyme (ACE) inhibitors for at least 36 h or after the last dose of an angiotensin receptor blocker (ARB). In naïve patients, we initiated a low dose of sacubitril/valsartan combination following patient stabilization. Before discharge, a 6-MWT was performed to evaluate patient's functional capacity, measuring total walked distance (in meters), oxygen saturation and heart rate at the beginning and at the end of the test; Borg Scale was applied to evaluate the intensity of dyspnoea. After discharge, follow-up visits at 1 and 6 months, 2D-echocardiography, blood tests and 6-MWT were performed to re-evaluate the efficacy of the treatment., Results: A total of 14 patients (85.7% males) were included. Mean age was 66.0 ± 10.3 years. Body mass index (BMI) was 29.9 ± 4.7 kg/m
2 . There were no differences in creatinine at admission compared with values at 1 and 6 months. Mean left ventricular ejection fraction (LVEF) was 28.7 ± 4.7% at baseline and increased to 33.5 ± 6.6% and 38.0 ± 2.9% at 1 and 6 months, respectively (p = .028). Total distance covered at 6-MWT increased over the study period (baseline: 227.4 ± 62.8 m; 6 months: 257.3 ± 65.2 m, p = .317) although the increase was not statistically significant., Conclusions: The present experience showed that angiotensin receptor-neprilysin inhibitor (ARNi) might represent a new valuable therapeutic strategy, even at the earlier stages of stabilized acute HF. Therefore, we suggest a clinical practice algorithm, to consider before discharge, which should be validated by further analyses.- Published
- 2019
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17. T2238C ANP gene variant and risk of recurrent acute coronary syndromes in an Italian cohort of ischemic heart disease patients.
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Rubattu S, De Giusti M, Farcomeni A, Abbolito S, Comito F, Cangianiello S, Greco ES, Dito E, Pagliaro B, Cotugno M, Stanzione R, Marchitti S, Bianchi F, Di Castro S, Battistoni A, Burocchi S, Caprinozzi M, Pierelli G, Sciarretta S, and Volpe M
- Subjects
- Aged, Alleles, Angina, Unstable drug therapy, Aspirin therapeutic use, Female, Humans, Italy, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Recurrence, Retrospective Studies, Risk Factors, Acute Coronary Syndrome genetics, Angina, Unstable genetics, Atrial Natriuretic Factor genetics, Myocardial Infarction genetics
- Abstract
Background: The role of C2238/atrial natriuretic peptide (ANP) minor allele, at the T2238C ANP gene variant, as a predisposing risk factor for acute cardiovascular events, has been previously reported. We aimed at evaluating, by a retrospective approach, the long-term impact of C2238/ANP-minor allele carrier status toward the risk of recurrent acute coronary syndromes (re-ACS) in an Italian cohort of ischemic heart disease patients., Methods: A total of 379 patients (males = 80.5%; mean age = 62.5 ± 9.2 years) presenting with ACS were retrospectively analyzed. Mean follow-up was 5.1 ± 3.5 years (range 1-26 years). Occurrence of new episodes of unstable angina, non-ST-segment elevation myocardial infarction and STE myocardial infarction over the years was recorded and compared between subjects not carrying and carrying C2238/ANP-minor allele., Results: At univariate analysis, C2238/ANP-minor allele carrier status and treatment with beta-blocker, aspirin and statin were associated with risk of re-ACS. Multivariate analysis confirmed that hypercholesterolemia (P < 0.0001) and C2238/ANP-minor allele carrier status (P < 0.05) were both significantly and independently associated with increased risk of re-ACS. Both treatments with beta-blocker and with statin were significantly associated with reduced risk of re-ACS (P = 0.01 and P < 0.01, respectively). Age above 55 years was associated with recurrence of ACS in C2238/ANP-minor allele carriers (hazard ratio 1.427, 95% confidence interval 1.066-1.911, P = 0.017). Kaplan-Meier curves confirmed highest risk of new events occurrence in C2238/ANP-minor allele carriers (P = 0.035)., Conclusions: The present results demonstrate that C2238/ANP-minor allele carrier status is an independent risk factor for ACS recurrence in an Italian cohort of ischemic heart disease patients over the long term, and they support the role of C2238/ANP-minor allele as a negative prognostic factor in coronary artery disease patients.
- Published
- 2016
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18. A Multicenter, Open-Label Phase II Clinical Trial of Combined MEK plus EGFR Inhibition for Chemotherapy-Refractory Advanced Pancreatic Adenocarcinoma.
- Author
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Ko AH, Bekaii-Saab T, Van Ziffle J, Mirzoeva OM, Joseph NM, Talasaz A, Kuhn P, Tempero MA, Collisson EA, Kelley RK, Venook AP, Dito E, Ong A, Ziyeh S, Courtin R, Linetskaya R, Tahiri S, and Korn WM
- Subjects
- Adenocarcinoma mortality, Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Benzimidazoles administration & dosage, Biomarkers, DNA, Neoplasm blood, Drug Resistance, Neoplasm, Erlotinib Hydrochloride administration & dosage, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Neoplasm Staging, Neoplastic Cells, Circulating, Pancreatic Neoplasms mortality, Retreatment, Adenocarcinoma drug therapy, Adenocarcinoma pathology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Molecular Targeted Therapy, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology
- Abstract
Purpose: On the basis of preclinical evidence of synergistic activity between MEK and EGFR inhibitors in pancreatic ductal adenocarcinoma (PDAC), we evaluated the safety and efficacy of selumetinib, a MEK1/2 inhibitor, plus erlotinib in patients with previously treated advanced PDAC., Experimental Design: In this single-arm phase II trial, eligible patients received the combination of erlotinib 100 mg plus selumetinib 100 mg daily in 3-week cycles. Study assessments included measurement of clinical outcomes, with a primary endpoint of overall survival, and exploration of potential molecular predictors of treatment benefit., Results: Forty-six patients were enrolled and received a median of two cycles (range, 1-7). Although no objective responses were observed, 19 patients (41%) showed evidence of stable disease for ≥6 weeks, and 13 of 34 patients (38%) had a CA19-9 decline ≥50%. Median progression-free survival was 1.9 months [95% confidence interval (CI), 1.4-3.3 months], with a median overall survival of 7.3 months (95% CI, 5.2-8.0 months). Common adverse events included rash, diarrhea, and nausea/vomiting. Patients with tumors exhibiting an epithelial phenotype (demonstrated by a high level of E-cadherin expression) were more likely to be sensitive to study treatment. Tumor-derived DNA was detectable in plasma from the majority of patients using next-generation digital DNA sequencing, and its relative abundance correlated with tumor burden., Conclusions: A therapeutic strategy of dual targeted inhibition of the MEK and EGFR pathways shows modest antitumor activity in pancreatic cancer. Specific molecular subtypes may derive greatest benefit from this combination. Further exploration, both with more potent MEK inhibitors and in molecularly enriched patient subsets, is warranted., (©2015 American Association for Cancer Research.)
- Published
- 2016
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19. A phase I trial of nab-paclitaxel, gemcitabine, and capecitabine for metastatic pancreatic cancer.
- Author
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Ko AH, Truong TG, Kantoff E, Jones KA, Dito E, Ong A, and Tempero MA
- Subjects
- Adenocarcinoma blood, Adenocarcinoma pathology, Aged, Albumin-Bound Paclitaxel, Albumins administration & dosage, Albumins adverse effects, Biomarkers, Tumor blood, CA-19-9 Antigen blood, Capecitabine, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Deoxycytidine analogs & derivatives, Disease Progression, Drug Administration Schedule, Female, Fluorouracil administration & dosage, Fluorouracil adverse effects, Fluorouracil analogs & derivatives, Humans, Kaplan-Meier Estimate, Male, Maximum Tolerated Dose, Middle Aged, Paclitaxel administration & dosage, Paclitaxel adverse effects, Pancreatic Neoplasms blood, Pancreatic Neoplasms pathology, Treatment Outcome, Gemcitabine, Adenocarcinoma drug therapy, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Pancreatic Neoplasms drug therapy
- Abstract
Background: Substantial antitumor activity has previously been demonstrated with the addition of nab-paclitaxel (Abraxane [Celgene, Summit, NJ]), an albumin-bound formulation of paclitaxel, to gemcitabine in patients with advanced pancreatic cancer. Given preclinical evidence of synergy when a fluoropyrimidine is added to gemcitabine plus a taxane in a sequence-specific schedule, we conducted a phase I study to evaluate the combination of nab-paclitaxel, gemcitabine, and capecitabine administered biweekly in patients with metastatic pancreatic adenocarcinoma., Materials and Methods: Patients with previously untreated metastatic pancreatic cancer and an ECOG performance status of 0-1 were eligible to participate. Study design utilized a 3 + 3 dose-escalation schema, with expanded cohort at maximum-tolerated dose (MTD). Treatment was administered in 14-day cycles, with capecitabine given on days 1-7 and both gemcitabine (at fixed-dose rate infusion) and nab-paclitaxel on day 4 of each cycle. Dose-limiting toxicity (DLT) definitions included grade 3-4 hematologic toxicities and grade 2-4 hand-foot syndrome, neuropathy, or diarrhea., Results: Fifteen patients were enrolled across two dose levels. Final MTD was established at nab-paclitaxel 100 mg/m(2), gemcitabine 750 mg/m(2), and capecitabine 750 mg/m(2) twice daily. Patients received a median of four treatment cycles (range 1-16). The most frequent adverse events (any grade) for the entire study cohort included fatigue, rash/hand-foot syndrome, nausea/vomiting, diarrhea, neuropathy, and elevated liver function tests. Ten patients (66.7 %) experienced at least one grade 3-4 adverse event. Grade 3-4 hematologic toxicities were uncommon. Two of 14 evaluable patients (14.3 %) exhibited a partial response, and 6 of 12 patients (50 %) with elevated CA19-9 at baseline had a ≥50 % biomarker decline., Conclusion: While well tolerated overall, this regimen demonstrated only modest antitumor activity in patients with metastatic pancreatic cancer. Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of gemcitabine/nab-paclitaxel. The lower doses used in the current study suggest that dose intensity may be a critical aspect to optimize multidrug regimens.
- Published
- 2012
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20. Optimizing the administration of fixed-dose rate gemcitabine plus capecitabine using an alternating-week schedule: a dose finding and early efficacy study in advanced pancreatic and biliary carcinomas.
- Author
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Ko AH, Espinoza AM, Jones KA, Venook AP, Bergsland EK, Kelley RK, Dito E, Ong A, Hanover CS, Coakley FV, and Tempero MA
- Subjects
- Adult, Aged, Biliary Tract Neoplasms mortality, Biliary Tract Neoplasms secondary, Capecitabine, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Female, Fluorouracil administration & dosage, Fluorouracil analogs & derivatives, Follow-Up Studies, Humans, Lymphatic Metastasis, Male, Maximum Tolerated Dose, Middle Aged, Neoplasm Staging, Pancreatic Neoplasms mortality, Pancreatic Neoplasms secondary, Survival Rate, Treatment Outcome, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biliary Tract Neoplasms drug therapy, Pancreatic Neoplasms drug therapy
- Abstract
Objectives: This multisite study sought to optimize the dosing, schedule, and administration of fixed-dose rate (FDR) gemcitabine plus capecitabine for advanced pancreatic and biliary tract cancers using an alternating-week dose schedule of both agents., Methods: Patients with previously untreated advanced pancreatic and biliary tract cancers with Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. For the dose-finding portion, a standard 3+3 dose-escalation schema was used, with the gemcitabine dose kept at 1000 mg/m(2) administered by FDR (10 mg/m(2)/min) on day 1 of each 14-day cycle, and capecitabine given on days 1 to 7 at doses ranging from 800 to 1500 mg/m(2) twice daily. Primary study objective was determination of maximum tolerated dose (MTD). The cohort at MTD was expanded for further efficacy assessment., Results: A total of 45 patients (median age 61 y; 93% pancreatic/7% biliary; 84% with metastatic disease) were enrolled. Median number of cycles received was 11.5. The MTD using this dose schedule was FDR gemcitabine 1000 mg/m(2) plus capecitabine 1000 mg/m(2) bid, due to a high incidence of late hand-foot syndrome observed at the next higher dose level. Most common nonhematologic adverse events related to treatment included nausea/vomiting (overall rate, 64%; all grade 1/2) and hand-foot syndrome (overall rate, 60%; grade 3, 22%). The incidence of grade 3/4 hematologic adverse events was 24%. Six of 41 evaluable patients (14.6%) had a partial response; 18 of 31 patients (58%) with elevated baseline CA 19-9 level had ≥50% biomarker decline during treatment. Estimated median time to tumor progression and overall survival were 5.5 and 9.8 months, respectively (5.5 and 10.1 mo in the metastatic pancreatic cancer cohort)., Conclusions: This dosing schedule of FDR gemcitabine plus capecitabine is active in patients with advanced pancreatobiliary cancers. Given its favorable toxicity profile and convenience, this regimen represents an appropriate front-line option for this patient population and may serve as the foundation on which new investigational agents are added in future trial design.
- Published
- 2012
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21. A survey on blood pressure levels and hypertension control in a sample of the Italian general population.
- Author
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De Giusti M, Dito E, Pagliaro B, Burocchi S, Laurino FI, Tocci G, Volpe M, and Rubattu S
- Subjects
- Adult, Aged, Aged, 80 and over, Awareness, Female, Health Surveys, Humans, Hypertension ethnology, Italy epidemiology, Male, Middle Aged, Prevalence, Risk Factors, Surveys and Questionnaires, Treatment Outcome, Antihypertensive Agents therapeutic use, Blood Pressure physiology, Hypertension drug therapy, Hypertension epidemiology
- Abstract
Background: Hypertension represents a major cardiovascular risk factor with relevant consequences on morbidity and mortality in the general population. An optimal control of blood pressure (BP) is far from being achieved., Aim: The objective of this study was to explore awareness of BP levels, prevalence of risk factors and status of hypertension control in a sample of the Italian general population., Methods: Subjects aged 18 years or older were enrolled on a voluntary basis during the 7th and 8th World Hypertension Days at our hospital centre, S. Andrea Hospital in Rome, and at other hospitals throughout the Italian Lazio region. Along with BP measurement, a short questionnaire was completed at the time of the interview., Results: Of 1165 individuals enrolled into the analysis, 71.7% were aware of their BP levels (82.5% among hypertensive patients). Within the whole cohort, 31.9% of subjects were under antihypertensive treatment, while the overall rate of subjects found to be hypertensive patients at our visit was 52.9% (n = 616). Among hypertensive patients taking antihypertensive drugs, 47.1% had controlled BP values with the remaining 52.9% showing uncontrolled hypertension. Mean systolic blood pressure (SBP) was 138.2 ± 20.7 mmHg and mean diastolic blood pressure (DBP) was 80.4 ± 11.3 mmHg in subjects receiving antihypertensive treatment. Among older hypertensive patients (71-94 years of age), only 76.9% were under treatment. Hypertensive males were more frequently treated than females in all age groups (p = 0.001). Smoking habit negatively affected efficacy of antihypertensive therapy in the age groups of 48-53 and 54-62 years (p = 0.008 and p = 0.01, respectively). Diabetic patients had higher mean SBP values than non-diabetic subjects (137.3 ± 22.1 vs 129.3 ± 18.2 mmHg, p = 0.02)., Conclusion: The results of our survey strongly support the need for a continuing educational effort aimed at providing correct advertisement of healthy lifestyles and awareness of adequate BP control. Based on our observations, particular attention has to be paid to women, younger subjects, elderly subjects and diabetic patients in order to reach appropriate BP control and reduction of cardiovascular risk in these subject categories.
- Published
- 2012
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22. IGF-1 and atherothrombosis: relevance to pathophysiology and therapy.
- Author
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Conti E, Musumeci MB, De Giusti M, Dito E, Mastromarino V, Autore C, and Volpe M
- Subjects
- Animals, Atherosclerosis prevention & control, Cardiovascular Agents adverse effects, Cardiovascular Agents therapeutic use, Cardiovascular Diseases drug therapy, Diabetes Mellitus drug therapy, Humans, Insulin-Like Growth Factor I adverse effects, Insulin-Like Growth Factor I therapeutic use, Mice, Recombinant Proteins adverse effects, Recombinant Proteins therapeutic use, Thrombosis prevention & control, Atherosclerosis physiopathology, Insulin-Like Growth Factor I physiology, Thrombosis physiopathology
- Abstract
IGF-1 (insulin-like growth factor-1) plays a unique role in the cell protection of multiple systems, where its fine-tuned signal transduction helps to preserve tissues from hypoxia, ischaemia and oxidative stress, thus mediating functional homoeostatic adjustments. In contrast, its deprivation results in apoptosis and dysfunction. Many prospective epidemiological surveys have associated low IGF-1 levels with late mortality, MI (myocardial infarction), HF (heart failure) and diabetes. Interventional studies suggest that IGF-1 has anti-atherogenic actions, owing to its multifaceted impact on cardiovascular risk factors and diseases. The metabolic ability of IGF-1 in coupling vasodilation with improved function plays a key role in these actions. The endothelial-protective, anti-platelet and anti-thrombotic activities of IGF-1 exert critical effects in preventing both vascular damage and mechanisms that lead to unstable coronary plaques and syndromes. The pro-survival and anti-inflammatory short-term properties of IGF-1 appear to reduce infarct size and improve LV (left ventricular) remodelling after MI. An immune-modulatory ability, which is able to suppress 'friendly fire' and autoreactivity, is a proposed important additional mechanism explaining the anti-thrombotic and anti-remodelling activities of IGF-1. The concern of cancer risk raised by long-term therapy with IGF-1, however, deserves further study. In the present review, we discuss the large body of published evidence and review data on rhIGF-1 (recombinant human IGF-1) administration in cardiovascular disease and diabetes, with a focus on dosage and safety issues. Perhaps the time has come for the regenerative properties of IGF-1 to be assessed as a new pharmacological tool in cardiovascular medicine.
- Published
- 2011
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23. A phase II study of bevacizumab plus erlotinib for gemcitabine-refractory metastatic pancreatic cancer.
- Author
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Ko AH, Venook AP, Bergsland EK, Kelley RK, Korn WM, Dito E, Schillinger B, Scott J, Hwang J, and Tempero MA
- Subjects
- Adult, Aged, Aged, 80 and over, Angiogenesis Inhibitors administration & dosage, Angiogenesis Inhibitors adverse effects, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bevacizumab, Deoxycytidine administration & dosage, Disease Progression, Drug Administration Schedule, Erlotinib Hydrochloride, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Pancreatic Neoplasms ethnology, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Quinazolines administration & dosage, Quinazolines adverse effects, Treatment Outcome, Gemcitabine, Antimetabolites, Antineoplastic administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Deoxycytidine analogs & derivatives, Drug Resistance, Neoplasm, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology
- Abstract
Purpose: No standard of care exists for patients with metastatic pancreatic cancer following progression on first-line chemotherapy. Based on potential for additive or synergistic activity by concurrent inhibition of VEGF and EGFR, we conducted a phase II study evaluating the combination of bevacizumab plus erlotinib in this patient population., Methods: Patients with metastatic pancreatic adenocarcinoma, ECOG performance status 0-1, and previous exposure to 1-3 systemic therapies (at least one gemcitabine-based) were eligible. Treatment consisted of bevacizumab 15 mg/kg every 21 days plus erlotinib 150 mg daily., Results: Thirty-six patients were enrolled, including eight who had previously received VEGF-targeted therapy and nine prior erlotinib. Median number of treatment cycles was 2 (range, 1-7). Common toxicities included rash (72%), diarrhea (25%), venous thromboembolic events (15%), and hypertension (11%). One patient demonstrated partial response and seven others stable disease for >2 cycles. CA19-9 decline ≥25% was observed in 4/26 patients with baseline levels >2x ULN. Estimated median time to progression was 40 days (95% CI, 35-41 days) and median survival 102 days (95% CI, 74-117 days), with a 6-month survival rate of 22%. Baseline concentration of circulating endothelial cells (CD45(-)/CD34(+)/CD31(+)) was inversely associated with overall survival., Conclusions: The combination of bevacizumab and erlotinib is safe but relatively ineffective in patients with gemcitabine-refractory metastatic pancreatic cancer. Future studies should focus on refining subsets of patients in this challenging population likely to benefit from treatment beyond first-line.
- Published
- 2010
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24. A phase II study evaluating bevacizumab in combination with fixed-dose rate gemcitabine and low-dose cisplatin for metastatic pancreatic cancer: is an anti-VEGF strategy still applicable?
- Author
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Ko AH, Dito E, Schillinger B, Venook AP, Xu Z, Bergsland EK, Wong D, Scott J, Hwang J, and Tempero MA
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal adverse effects, Antibodies, Monoclonal, Humanized, Bevacizumab, Deoxycytidine administration & dosage, Female, Humans, Male, Middle Aged, Neoplasm Metastasis, Pancreatic Neoplasms pathology, Survival Analysis, Gemcitabine, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cisplatin administration & dosage, Deoxycytidine analogs & derivatives, Pancreatic Neoplasms drug therapy, Vascular Endothelial Growth Factor A antagonists & inhibitors
- Abstract
Background: The role of bevacizumab, a recombinant humanized monoclonal antibody directed against vascular endothelial growth factor, in the treatment of pancreatic cancer remains unclear. The objectives of this study were to determine safety and efficacy in chemotherapy-naive patients with metastatic pancreatic cancer receiving bevacizumab in combination with fixed-dose rate (FDR) gemcitabine and low-dose cisplatin., Methods: Eligible patients received gemcitabine 1,000 mg/m2 at FDR infusion (10 mg/m(2) per minute), cisplatin 20 mg/m(2), and bevacizumab 10 mg/kg, on days 1 and 15 of a 28-day cycle. Patients were monitored by computed tomography scans every two cycles and monthly serum CA19-9 measurements., Results: Of 52 patients eligible for analysis, ten (19.2%) had an unconfirmed response and 30 (57.7%) had stable disease. Of 35 patients with elevated baseline CA19-9 levels, 20 (57.1%) had > or = 50% biomarker decline during treatment. Median time to tumor progression was 6.6 months and median survival was 8.2 months (estimated 1-year survival, 36%). Grade 3/4 toxicities possibly related to bevacizumab included thromboembolic events (15.1%), hypertension (13.2%), gastrointestinal bleeding (9.4%), cardiac events (7.5%), and bowel perforation (5.7%). Plasma vascular endothelial growth factor and basic fibroblast growth factor levels and circulating tumor cell concentration did not correlate with overall survival, either at baseline or after 2 months of therapy., Conclusions: This bevacizumab-containing study regimen is modestly effective in patients with metastatic pancreatic cancer, although occasional serious complications may occur. Given the negative results of CALGB 80303, future efforts should be focused on identifying those specific patients who are most likely to benefit from bevacizumab-based therapy.
- Published
- 2008
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25. Excess toxicity associated with docetaxel and irinotecan in patients with metastatic, gemcitabine-refractory pancreatic cancer: results of a phase II study.
- Author
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Ko AH, Dito E, Schillinger B, Venook AP, Bergsland EK, and Tempero MA
- Subjects
- Adenocarcinoma mortality, Adult, Aged, Camptothecin administration & dosage, Camptothecin analogs & derivatives, Camptothecin toxicity, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Docetaxel, Drug Resistance, Neoplasm, Female, Humans, Irinotecan, Kaplan-Meier Estimate, Male, Middle Aged, Pancreatic Neoplasms mortality, Taxoids administration & dosage, Taxoids toxicity, Gemcitabine, Adenocarcinoma drug therapy, Adenocarcinoma secondary, Antineoplastic Combined Chemotherapy Protocols toxicity, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms pathology
- Abstract
Background: No therapeutic standard of care exists for patients with advanced pancreatic cancer who progress following first-line treatment with a gemcitabine-based regimen. There is evidence of synergistic activity between docetaxel and irinotecan, and the combination of these two agents has shown promising efficacy in the first-line setting for advanced pancreatic cancer. We, therefore, evaluated this regimen in patients with gemcitabine-refractory disease., Methods: Eligible patients with metastatic pancreatic adenocarcinoma were required to have an elevated serum CA19-9 (> 2x ULN) and exposure to one or two prior chemotherapy regimens, including one gemcitabine-based. Treatment consisted of docetaxel 65 mg/m2 and irinotecan 160 mg/m2, both administered every 21 days. Serum CA19-9 levels were measured at the start of each treatment cycle and CT scans performed after every two cycles., Results: Fourteen patients were enrolled before the study was closed due to excess toxicity. The most common grade 3/4 toxicities included neutropenia/leukopenia, nausea and vomiting, and diarrhea. Fully half of patients received only 1 treatment cycle, with a median time to treatment failure of 36 days. No objective responses were observed, although 3 patients had stable disease for at least 6 cycles. Overall survival for the entire cohort was 134 days, with a 6-month survival rate of 36%., Conclusions: The combination of docetaxel and irinotecan given on a 21-day cycle is associated with excess toxicity in gemcitabine-refractory patients with advanced pancreatic cancer. Although select patients may benefit from treatment, the overall risk:benefit ratio is unfavorable, and other dosing regimens and therapeutic options should be explored in this setting.
- Published
- 2008
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26. A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer.
- Author
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Ko AH, Quivey JM, Venook AP, Bergsland EK, Dito E, Schillinger B, and Tempero MA
- Subjects
- Adult, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic administration & dosage, California epidemiology, Cisplatin administration & dosage, Comorbidity, Deoxycytidine administration & dosage, Deoxycytidine analogs & derivatives, Dose-Response Relationship, Drug, Female, Gastrointestinal Diseases epidemiology, Humans, Incidence, Male, Middle Aged, Neoplasm Recurrence, Local prevention & control, Pancreatic Neoplasms surgery, Prognosis, Radiation-Sensitizing Agents administration & dosage, Risk Assessment methods, Risk Factors, Survival Analysis, Survival Rate, Treatment Outcome, Gemcitabine, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Neoplasm Recurrence, Local mortality, Pancreatic Neoplasms mortality, Pancreatic Neoplasms therapy, Radiation Injuries epidemiology, Radiotherapy, Adjuvant mortality
- Abstract
Purpose: The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population., Methods and Materials: Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m(2) at 10 mg/m(2)/min) plus cisplatin 20 mg/m(2) on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m(2) orally twice daily on the day of radiation) as a radiosensitizer., Results: A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months., Conclusions: A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.
- Published
- 2007
- Full Text
- View/download PDF
27. Phase II study of fixed dose rate gemcitabine with cisplatin for metastatic adenocarcinoma of the pancreas.
- Author
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Ko AH, Dito E, Schillinger B, Venook AP, Bergsland EK, and Tempero MA
- Subjects
- Adenocarcinoma ethnology, Adult, Aged, Antimetabolites, Antineoplastic adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, CA-19-9 Antigen blood, Cisplatin administration & dosage, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Disease Progression, Disease-Free Survival, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Male, Middle Aged, Pancreatic Neoplasms ethnology, Research Design, Survival Analysis, Tomography, X-Ray Computed, Treatment Outcome, Gemcitabine, Adenocarcinoma drug therapy, Antimetabolites, Antineoplastic administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Deoxycytidine analogs & derivatives, Pancreatic Neoplasms drug therapy
- Abstract
Purpose: Although gemcitabine remains the standard of care for patients with advanced pancreatic cancer, additional improvements may be realized by combining therapeutic agents with synergistic activity, and optimizing drug delivery using pharmacokinetic principles such as fixed dose rate (FDR) infusion. The objectives of this study were to determine safety and efficacy in patients with metastatic pancreatic cancer treated with FDR gemcitabine in combination with low-dose cisplatin., Patients and Methods: Chemotherapy-naive patients with metastatic pancreatic adenocarcinoma were treated with a combination of gemcitabine 1,000 mg/m2 at 10 mg/m2/min together with cisplatin 20 mg/m2 on days 1 and 8 of a 21-day cycle. Patient follow-up was performed using computerized tomographic scans and serial CA 19-9 measurements., Results: A total of 51 patients were enrolled onto the study, with a median follow-up time of 215 days. Twenty-two of 40 patients (55.0%) with a baseline serum CA 19-9 level > or = 2x the upper limit of normal demonstrated a > or = 50% biomarker decline during treatment. Nine of 47 patients (19.1%) with measurable disease achieved a partial response, and 28 patients (59.6%) had disease stabilization for at least two treatment cycles. Median time to progression was 3.9 months and median survival was 7.1 months, with an estimated 1-year survival rate of 29%. The most frequently reported grade 3 or 4 adverse events were neutropenia (52.9%) and thrombocytopenia (15.7%). Most patients were switched to an every-other-week dosing schedule., Conclusion: The combination of FDR gemcitabine and cisplatin is well tolerated and appears to be an acceptable, albeit not clearly superior, alternative to other gemcitabine/platinum regimens for the treatment of metastatic pancreatic cancer.
- Published
- 2006
- Full Text
- View/download PDF
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