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Clinical Research Papers:

Imatinib and polypharmacy in very old patients with chronic myeloid leukemia: effects on response rate, toxicity and outcome

Alessandra Iurlo _, Alessandro Nobili, Roberto Latagliata, Cristina Bucelli, Fausto Castagnetti, Massimo Breccia, Elisabetta Abruzzese, Daniele Cattaneo, Carmen Fava, Dario Ferrero, Antonella Gozzini, Massimiliano Bonifacio, Mario Tiribelli, Patrizia Pregno, Fabio Stagno, Paolo Vigneri, Mario Annunziata, Francesco Cavazzini, Gianni Binotto, Giovanna Mansueto, Sabina Russo, Franca Falzetti, Enrico Montefusco, Gabriele Gugliotta, Sergio Storti, Ada M. D’Addosio, Luigi Scaffidi, Laura Cortesi, Michele Cedrone, Antonella Russo Rossi, Paolo Avanzini, Endri Mauro, Antonio Spadea, Francesca Celesti, Gianfranco Giglio, Alessandro Isidori, Monica Crugnola, Elisabetta Calistri, Federica Sorà, Giovanna Rege-Cambrin, Simona Sica, Luigiana Luciano, Sara Galimberti, Ester M. Orlandi, Monica Bocchia, Mauro Tettamanti, Giuliana Alimena, Giuseppe Saglio, Gianantonio Rosti, Pier Mannuccio Mannucci and Agostino Cortelezzi

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Oncotarget. 2016; 7:80083-80090. https://doi.org/10.18632/oncotarget.11657

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Abstract

Alessandra Iurlo1, Alessandro Nobili2, Roberto Latagliata3, Cristina Bucelli1, Fausto Castagnetti4, Massimo Breccia3, Elisabetta Abruzzese5, Daniele Cattaneo1, Carmen Fava6, Dario Ferrero7, Antonella Gozzini8, Massimiliano Bonifacio9, Mario Tiribelli10, Patrizia Pregno11, Fabio Stagno12, Paolo Vigneri12, Mario Annunziata13, Francesco Cavazzini14, Gianni Binotto15, Giovanna Mansueto16, Sabina Russo17, Franca Falzetti18, Enrico Montefusco19, Gabriele Gugliotta4, Sergio Storti20, Ada M. D’Addosio21, Luigi Scaffidi9, Laura Cortesi2, Michele Cedrone22, Antonella Russo Rossi23, Paolo Avanzini24, Endri Mauro25, Antonio Spadea26, Francesca Celesti27, Gianfranco Giglio28, Alessandro Isidori29, Monica Crugnola30, Elisabetta Calistri31, Federica Sorà32, Giovanna Rege-Cambrin6, Simona Sica32, Luigiana Luciano33, Sara Galimberti34, Ester M. Orlandi35, Monica Bocchia36, Mauro Tettamanti2, Giuliana Alimena3, Giuseppe Saglio6, Gianantonio Rosti4, Pier Mannuccio Mannucci37 and Agostino Cortelezzi1

1 Oncohematology Division, IRCCS Ca’ Granda - Maggiore Policlinico Hospital Foundation, University of Milan, Milan, Italy

2 Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche “Mario Negri”, Milan, Italy

3 Department of Cellular Biotechnologies and Hematology, University “La Sapienza” of Rome, Rome, Italy

4 Institute of Hematology “L. and A. Seràgnoli”, Department of Experimental, Diagnostic and Specialty Medicine, “S. Orsola-Malpighi” University Hospital, University of Bologna, Bologna, Italy

5 Hematology Unit, Sant’Eugenio Hospital, Rome, Italy

6 Division of Hematology and Internal Medicine, University of Turin, “San Luigi Gonzaga” University Hospital, Orbassano, Turin, Italy

7 Hematology Unit, University of Turin, Turin, Italy

8 Haematology, AOU Careggi, University of Firenze, Firenze, Italy

9 Department of Medicine, Section of Hematology, University of Verona, Verona, Italy

10 Division of Hematology and BMT, Azienda Ospedaliero - Universitaria di Udine, Udine, Italy

11 Hematology Unit, Azienda Ospedaliero Universitaria Città della Salute e della Scienza, Turin, Italy

12 Hematology Unit, Ferrarotto Hospital, Catania, Italy

13 Hematology Unit, Cardarelli Hospital, Naples, Italy

14 Hematology Unit, University of Ferrara, Ferrara, Italy

15 Hematology Unit, University of Padova, Padova, Italy

16 Department of Onco-Hematology, IRCCS-CROB, Rionero in Vulture, Italy

17 Hematology Unit, AOU G. Martino, Messina, Italy

18 Division of Hematology and Clinical Immunology, Department of Medicine, University of Perugia, Perugia, Italy

19 Hematology Unit, Sant’Andrea Hospital, Rome, Italy

20 Onco-Hematology Unit, Università Cattolica Giovanni Paolo II, Campobasso, Italy

21 Immunohematology and Trasfusional Medicine Division, S. Pietro Fatebenefratelli Hospital, Rome, Italy

22 Hematology Unit, S. Giovanni Hospital, Rome, Italy

23 Hematology and Transplants Unit, University of Bari, Bari, Italy

24 Hematology, Arcispedale Santa Maria Nuova - IRCCS, Reggio Emilia, Italy

25 Department of Internal Medicine, Pordenone General Hospital, Pordenone, Italy

26 Hematology and Stem Cell Transplantation Unit, Regina Elena Institute, Rome, Italy

27 Hematology Unit, Belcolle Hospital, Viterbo, Italy

28 Hematology Unit, Campobasso Hospital, Campobasso, Italy

29 Hematology Unit, Pesaro Hospital, Pesaro, Italy

30 Hematology and BMT Unit, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy

31 Hematology Unit, Treviso Hospital, Treviso, Italy

32 Institute of Hematology, Università Cattolica Sacro Cuore, Rome, Italy

33 Hematology Unit, ‘‘Federico II’’ Hospital, University of Naples, Naples, Italy

34 Department of Clinical and Experimental Medicine, Section of Hematology - University of Pisa, Pisa, Italy

35 Oncology-Hematology Department, Hematology Unit, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

36 Hematology Unit, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena, Italy

37 Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Ca’ Granda - Maggiore Policlinico Hospital Foundation and University of Milan, Milan, Italy

Correspondence to:

Alessandra Iurlo, email:

Keywords: chronic myeloid leukemia; comorbidities; imatinib; old patients; polypharmacy

Received: June 07, 2016 Accepted: July 13, 2016 Published: August 27, 2016

Abstract

Background: About 40% of all patients with chronic myeloid leukemia are currently old or very old. They are effectively treated with imatinib, even though underrepresented in clinical studies. Furthermore, as it happens in the general population, they often receive multiple drugs for associated chronic illnesses. Aim of this study was to assess whether or not in imatinib-treated patients aged >75 years the exposure to polypharmacy (5 drugs or more) had an impact on cytogenetic and molecular response rates, event-free and overall survival, as well as on hematological or extra-hematological toxicity.

Methods: 296 patients at 35 Italian hematological institutions were evaluated.

Results: Polypharmacy was reported in 107 patients (36.1%), and drugs more frequently used were antiplatelets, diuretics, proton pump inhibitors, ACE-inhibitors, beta-blockers, calcium channel blockers, angiotensin II receptors blockers, statins, oral hypoglycemic drugs and alpha blockers. Complete cytogenetic response was obtained in 174 patients (58.8%), 78 (26.4%) within 6 month, 63 (21.3%) between 7 and 12 months. Major molecular response was obtained in 153 patients (51.7%), 64 (21.6%) within the 12 month. One hundred and twenty-eight cases (43.2%) of hematological toxicity were recorded, together with 167 cases (56.4%) of extra-hematological toxicity. Comparing patients exposed to polypharmacy to those without, no difference was observed pertaining to the dosage of imatinib, cytogenetic and molecular responses and hematological and extra-hematological toxicity.

Conclusion: Notwithstanding the several interactions reported in the literature between imatinib and some of the medications considered herewith, this fact does not seem to have a clinical impact on response rate and outcome.


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