Completely disabled Cannot carry on any selfcare Totally confined to bed or chair

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Algoritmo decisionale per la gestione della neutropenia febbrile U.O. Oncologia Medica Pisa

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BIBLIOGRAFIA

1. Bonadonna G, Cuna GR Della, Valagussa P. Medicina Oncologica.; 2007.

2. Gianluigi Castoldi VL. Malattie del sangue e degli organi ematopoietici -. sesta

edizione,2013

3. Weycker D, Malin J, Edelsberg J, Glass a, Gokhale M, Oster G. Cost of neutropenic complications of chemotherapy. Ann. Oncol. 2008;19(3):454-60.

4. Lima SSS, França MS, Godoi CCG, et al. Neutropenic patients and their infectious complications at a University Hospital. Rev. Bras. Hematol. Hemoter. 2013;35(1):18-22. doi:10.5581/1516-8484.20130009.

5. Kuderer NM, Dale DC, Crawford J, Cosler LE, Lyman GH. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer 2006;106(10):2258-66.

6. National Cancer Institute, Common terminology criteria for adverse events v3. 0 (CTCAE). Cancer 2006;0:0-71.

7. Crawford J, Dale DC, Kuderer NM, et al. Risk and timing of neutropenic events in adult cancer patients receiving chemotherapy: the results of a prospective nationwide study of oncology practice. J. Natl. Compr. Canc. Netw. 2008;6(2):109- 18. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18319047.

8. National Cancer Institute, Common Terminology Criteria for Adverse Events ( CTCAE v. 4.03). 2010;2009.

74

9. C. R. Flowers, J. Seidenfeld, E. J. Bow, C. Karten, C. Gleason, D. K. Hawley, N. M. Kuderer, A. a Langston, K. a Marr, K. V. I. Rolston, and S. D. Ramsey, “Antimicrobial prophylaxis and outpatient management of fever and neutropenia in

adults treated for malignancy: American Society of Clinical Oncology clinical practice guideline.,” J. Clin. Oncol., vol. 31, no. 6, pp. 794–810, Feb. 2013.

10. J. J. Vehreschild, a Böhme, O. a Cornely, C. Kahl, M. Karthaus, K. Kreuzer, G. Maschmeyer, S. Mousset, V. Ossendorf, O. Penack, M. J. G. T. Vehreschild, and J. Bohlius, “Prophylaxis of infectious complications with colony-stimulating factors

in adult cancer patients undergoing chemotherapy-evidence-based guidelines from the Infectious Diseases Working Party AGIHO of the German Society for Haematology and Medical Oncology ,” Ann. Oncol., vol. 25, no. 9, pp. 1709–1718,

Sep. 2014.

11. J. C. et Al., “Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer,” N.

Engl. J. Med., 1991

12. Aapro MS, Cameron DA, Pettengell R, et al. EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy- induced febrile neutropenia in adult patients with lymphomas and solid tumours.

Eur. J. Cancer 2006;42:2433-2453.

13. M. S. Aapro, J. Bohlius, D. a Cameron, L. Dal Lago, J. P. Donnelly, N. Kearney, G. H. Lyman, R. Pettengell, V. C. Tjan-Heijnen, J. Walewski, D. C. Weber, and C. Zielinski, “2010 update of EORTC guidelines for the use of granulocyte-colony

75

neutropenia in adult patients with lymphoproliferative disorders and solid tumours.,” Eur. J. Cancer, vol. 47, no. 1, pp. 8–32, Jan. 2011.

14. Linee guida tossicità ematologica ,Associazione Italiana di Oncologia Medica, 2013.

15. Lyman GH, Lyman CH, Agboola O. Risk models for predicting chemotherapy- induced neutropenia. Oncologist 2005;10(6):427-37.

16. Crawford J, Dale DC, Lyman GH. Chemotherapy-Induced Neutropenia: Risks, Consequences, and New Directions for Its Management. Cancer 2004;100:228- 237.

17. Crawford J, Glaspy JA, Stoller RG, et al. Final results of a placebo-controlled study of filgrastim in small-cell lung cancer: exploration of risk factors for febrile neutropenia. Support. Cancer Ther. 2005;3:36-46.

18. Baker J, Ajani J, Scotté F, et al. Docetaxel-related side effects and their management. Eur. J. Oncol. Nurs. 2009;13:49-59. doi:10.1016/j.ejon.2008.10.003.

19. Pirker R, Pereira JR, Szczesna A, et al. Cetuximab plus Chemotherapy in Patients

with Advanced Non-Small-Cell Lung Cancer (FLEX): An Open-Label Randomised Phase III Trial.; 2009:1525-1531. doi:10.1016/S0140-6736(09)60569-9.

20. Sandler A, Gray R, Perry MC, et al. Paclitaxel-Carboplatin Alone or with

Bevacizumab for Non-Small-Cell Lung Cancer.; 2006:2542-2550. doi:10.1056/NEJMoa061884.

76

22. Shayne M, Culakova E, Wolff D, et al. Dose intensity and hematologic toxicity in older breast cancer patients receiving systemic chemotherapy. Cancer 2009;115:5319-5328.

23. Dranitsaris G, Rayson D, Vincent M, et al. Identifying Patients at High Risk for

Neutropenic Complications during Chemotherapy for Metastatic Breast Cancer with Doxorubicin or Pegylated Liposomal Doxorubicin: The Development of a Prediction Model.; 2008:369-374.

24. Trillet-Lenoir V, Green J, Manegold C, et al. Recombinant granulocyte colony stimulating factor reduces the infectious complications of cytotoxic chemotherapy.

Eur. J. Cancer 1993;29A:319-24. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7691119.

25. Vogel CL, Wojtukiewicz MZ, Carroll RR, et al. First and subsequent cycle use of pegfilgrastim prevents febrile neutropenia in patients with breast cancer: A multicenter, double-blind, placebo-controlled phase III study. J. Clin. Oncol. 2005;23:1178-1184.

26. Timmer-Bonte JNH, Adang EMM, Smit HJM, et al. Cost-effectiveness of adding granulocyte colony-stimulating factor to primary prophylaxis with antibiotics in small-cell lung cancer. J. Clin. Oncol. 2006;24:2991-2997. doi:10.1200/JCO.2005.04.3281.

27. Crawford J, Armitage J, Balducci L, Becker PS, Blayney DW, Cataland SR, Heaney ML, Hudock S, Kloth DD, Kuter DJ, Lyman GH, McMahon B, Rugo HS, Saad AA, Schwartzberg LS, Shayani S, Steensma DP, Talbott M, Vadhan-Raj S, Westervelt P, Westmoreland M, Dwyer M, Ho M; National comprehensive cancer network. Myeloid growth factors. J Natl Compr Canc Netw. 2014

77

28. J. Crawford, H. Kreisman, H. Garewal, S. E. Jones, D. Shoemaker, M. R. Pupa, S. Armstrong, D. Tomita, and G. Dziem, “Original article The impact of Filgrastim

schedule variation on hematopoietic recovery post-chemotherapy,” no. December 1991, pp. 1117–1124, 1997.

29. Smith TJ, Khatcheressian J, Lyman GH, et al. 2006 update of recommendations for the use of white blood cell growth factors: an evidence-based clinical practice guideline. J. Clin. Oncol. 2006;24:3187-3205.

30. Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clin. Infect. Dis. 2002;34:730-751. doi:10.1086/339215.

31. Biganzoli L, Untch M, Skacel T, Pico JL. Neulasta (pegfilgrastim): A once-per- cycle option for the management of chemotherapy-induced neutropenia. In:

Seminars in Oncology.Vol 31.; 2004:27-34.

32. Jain KK. Sweet’s syndrome associated with granulocyte colony-stimulating factor.

Cutis. 1996.

33. J. de Naurois, I. Novitzky-Basso, M. J. Gill, F. M. Marti, M. H. Cullen, and F. Roila, “Management of febrile neutropenia: ESMO Clinical Practice Guidelines.,”

Ann. Oncol., vol. 21 Suppl 5, no. Supplement 5, pp. v252–6, May 2010.

34. A. G. Freifeld, E. J. Bow, K. a Sepkowitz, M. J. Boeckh, J. I. Ito, C. a Mullen, I. I. Raad, K. V Rolston, J.-A. H. Young, J. R. Wingard, and Infectious Diseases Society of America, “Clinical practice guideline for the use of antimicrobial agents

in neutropenic patients with cancer: 2010 update by the infectious diseases society of America.,” Clin. Infect. Dis., vol. 52, no. 4, pp. e56–93, Feb. 2011.

78

35. Segal B, Freifeld A. Prevention and treatment of cancer-related infections. J. … 2008. Available at: http://www.ncbi.nlm.nih.gov/pubmed/18319048.

36. J. Klastersky, M. Paesmans, E. B. Rubenstein, M. Boyer, L. Elting, R. Feld, J. Gallagher, J. Herrstedt, B. Rapoport, K. Rolston, and J. Talcott, “The Multinational

Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.,” J. Clin.

Oncol., vol. 18, no. 16, pp. 3038–51, Aug. 2000.

37. NCCN, Clinical Practice Guidelines, Prevention and treatment of cancer-related indìfections. 2014.

38. M. Wadhwa, C. Bird, T. Dougall, P. Rigsby, A. Bristow, R. Thorpe, B. Lane, S. Mimms, and P. Bar, “Report on a Collaborative study for proposed 1 st

International standard for PEGylated G-CSF ( PEG-G-CSF ),” no. October, pp. 1– 39, 2013.

39. P. Jenkins, J. Scaife, and S. Freeman, “Validation of a predictive model that identifies patients at high risk of developing febrile neutropaenia following chemotherapy for breast cancer.,” Ann. Oncol., vol. 23, no. 7, pp. 1766–71, Jul.

2012.

40. P. Jenkins and S. Freeman, “Pretreatment haematological laboratory values predict for excessive myelosuppression in patients receiving adjuvant FEC chemotherapy for breast cancer.,” Ann. Oncol., vol. 20, no. 1, pp. 34–40, Jan. 2009.

79

41. M. Martín, a Lluch, M. a Seguí, a Ruiz, M. Ramos, E. Adrover, a Rodríguez- Lescure, R. Grosse, L. Calvo, C. Fernandez-Chacón, M. Roset, a Antón, D. Isla, P. M. del Prado, L. Iglesias, J. Zaluski, a Arcusa, J. M. López-Vega, M. Muñoz, and J. R. Mel, “Toxicity and health-related quality of life in breast cancer patients

receiving adjuvant docetaxel, doxorubicin, cyclophosphamide (TAC) or 5- fluorouracil, doxorubicin and cyclophosphamide (FAC): impact of adding primary prophylactic granulocyte-colony sti,” Ann. Oncol., vol. 17, no. 8, pp. 1205–12, Aug. 2006.

42. J. Alexandre, E. Rey, V. Girre, S. Grabar, a Tran, V. Montheil, F. Rabillon, V. Dieras, V. Jullien, P. Hérait, G. Pons, J.-M. Treluyer, and F. Goldwasser, “Relationship between cytochrome 3A activity, inflammatory status and the risk of

docetaxel-induced febrile neutropenia: a prospective study.,” Ann. Oncol., vol. 18, no. 1, pp. 168–72, Jan. 2007.

43. D. Rischin, “Phase I and pharmacokinetic study of docetaxel in combination with epirubicin and cyclophosphamide in advanced cancer: dose escalation possible with granulocyte colony-stimulating factor, but not with prophylactic antibiotics,” Ann.

Oncol., vol. 13, no. 11, pp. 1810–1818, Nov. 2002.

44. G. von Minckwitz, S. Kümmel, a du Bois, W. Eiermann, H. Eidtmann, B. Gerber, J. Hilfrich, J. Huober, S. D. Costa, C. Jackisch, S.-T. Grasshoff, S. Vescia, T. Skacel, S. Loibl, K. M. Mehta, and M. Kaufmann, “Pegfilgrastim +/- ciprofloxacin

for primary prophylaxis with TAC (docetaxel/doxorubicin/cyclophosphamide) chemotherapy for breast cancer. Results from the GEPARTRIO study.,” Ann.

80

45. O. Teuffel, M. C. Ethier, S. M. H. Alibhai, J. Beyene, and L. Sung, “Outpatient management of cancer patients with febrile neutropenia: a systematic review and meta-analysis.,” Ann. Oncol., vol. 22, no. 11, pp. 2358–65, Nov. 2011.

46. M. J. Piccart, P. Bruning, J. Wildiers, A. Awada, J. H. Schornagel, J. Thomas, E. Tomiak, S. Bartholomeus, P. O. Witteveen, and R. Paridaens, “Original article An

EORTC pilot study of filgrastim ( recombinant human granulocyte colony stimulating factor ) as support to a high dose-intensive epiadriamycin- advanced or metastatic breast cancer,” pp. 673–677, 1995

47. O. Penack, D. Buchheidt, M. Christopeit, M. von Lilienfeld-Toal, G. Massenkeil, M. Hentrich, H. Salwender, H.-H. Wolf, and H. Ostermann, “Management of sepsis in neutropenic patients: guidelines from the infectious diseases working party of the German Society of Hematology and Oncology.,” Ann. Oncol., vol. 22, no. 5, pp.

1019–29, May 2011

48. C. Imai, R. Kurimoto, E. Sakaida, Y. Tada, I. Sekine, T. Suzuki, H. Nakasa, N. Ariyoshi, Y. Takiguchi, and I. Ishii, “O2-010 * Investigation About Risk Factors of

Profound Neutropenia By Amrubicin Hydrochloride Therapy for Small Cell Lung Cancer,” Ann. Oncol., vol. 24, no. suppl 9, pp. ix46–ix46, Nov. 2013.

49. V. C. Souza-Dantas, J. I. F. Salluh, and M. Soares, “Impact of neutropenia on the outcomes of critically ill patients with cancer: a matched case-control study.,” Ann.

Oncol., vol. 22, no. 9, pp. 2094–100, Sep. 2011

50. B. Desablens, L. Sensebe, T. Lamy, C. Ghandour, and M. Boasson, “Original article Home treatment of febrile neutropenia : An empirical oral antibiotic regimen,” pp. 485–487, 1991.

51. C. Chao, J. H. Page, S.-J. Yang, R. Rodriguez, J. Huynh, and V. M. Chia, “History of chronic comorbidity and risk of chemotherapy-induced febrile neutropenia in

81

cancer patients not receiving G-CSF prophylaxis.,” Ann. Oncol., vol. 25, no. 9, pp. 1821–9, Sep. 2014.

52. J. Klastersky, “Clinical case Fever and neutropenia during intensive chemotherapy,” pp. 603–606, 1993.

53. D. Y. Aksoy, M. D. Tanriover, O. Uzun, P. Zarakolu, S. Ercis, S. Ergüven, a Oto, U. Kerimoglu, M. Hayran, and O. Abbasoglu, “Diarrhea in neutropenic patients: a prospective cohort study with emphasis on neutropenic enterocolitis.,” Ann. Oncol.,

vol. 18, no. 1, pp. 183–9, Jan. 2007.

54. S. Schelenz, D. Giles, and S. Abdallah, “Epidemiology, management and economic impact of febrile neutropenia in oncology patients receiving routine care at a regional UK cancer centre.,” Ann. Oncol., vol. 23, no. 7, pp. 1889–93, Jul. 2012

55. G. Maschmeyer, J. Carratalà, D. Buchheidt, a Hamprecht, C. P. Heussel, C. Kahl, J. Lorenz, S. Neumann, C. Rieger, M. Ruhnke, H. Salwender, M. Schmidt-Hieber, and E. Azoulay, “Diagnosis and antimicrobial therapy of lung infiltrates in febrile

neutropenic patients (allogeneic SCT excluded): updated guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO),” Ann. Oncol., pp. 1–12, May 2014.

56. P. Gascon, U. Fuhr, F. Sörgel, M. Kinzig-Schippers, a Makhson, S. Balser, S. Einmahl, and M. Muenzberg, “Development of a new G-CSF product based on biosimilarity assessment.,” Ann. Oncol., vol. 21, no. 7, pp. 1419–29, Jul. 2010.

57. M. Ruhnke, a Böhme, D. Buchheidt, O. Cornely, K. Donhuijsen, H. Einsele, R. Enzensberger, H. Hebart, C. P. Heussel, M. Horger, H. Hof, M. Karthaus, W. Krüger, G. Maschmeyer, O. Penack, J. Ritter, and S. Schwartz, “Diagnosis of

invasive fungal infections in hematology and oncology--guidelines from the Infectious Diseases Working Party in Haematology and Oncology of the German

82

Society for Haematology and Oncology (AGIHO).,” Ann. Oncol., vol. 23, no. 4, pp.

823–33, Apr. 2012.

58. Y. Lalami, M. Paesmans, F. Muanza, M. Barette, B. Plehiers, L. Dubreucq, a Georgala, and J. Klastersky, “Can we predict the duration of chemotherapy-induced

neutropenia in febrile neutropenic patients, focusing on regimen-specific risk factors? A retrospective analysis.,” Ann. Oncol., vol. 17, no. 3, pp. 507–14, Mar.

2006.

59. F. a. Holmes, S. E. Jones, J. O’Shaughnessy, S. Vukelja, T. George, M. Savin, D. Richards, J. Glaspy, L. Meza, G. Cohen, M. Dhami, D. R. Budman, J. Hackett, M. Brassard, B. B. Yang, and B. C. Liang, “Comparable efficacy and safety profiles of

once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy- induced neutropenia: a multicenter dose-finding study in women with breast cancer,” Ann. Oncol., vol. 13, no. 6, pp. 903–909, Jun. 2002

60. M. D. Green, “A randomized double-blind multicenter phase III study of fixed-dose single-administration pegfilgrastim versus daily filgrastim in patients receiving myelosuppressive chemotherapy,” Ann. Oncol., vol. 14, no. 1, pp. 29–35, Jan.

2003.

61. P. L. R. Mitchell, “A phase II study of escalated-dose docetaxel with granulocyte colony-stimulating factor support in patients with advanced breast cancer,” Ann.

Oncol., vol. 15, no. 4, pp. 585–589, Apr. 2004.

62. P. L. R. Mitchell, “A phase I dose-escalation study of docetaxel with granulocyte colony-stimulating factor support in patients with solid tumours,” Ann. Oncol., vol. 14, no. 5, pp. 788–794, May 2003.

63. Weycker D, Barron R, Edelsberg J, Kartashov A, Legg J, Glass AG. Risk and consequences of chemotherapy-induced neutropenic complications in patients

83

receiving daily filgrastim: the importance of duration of prophylaxis. BMC Health Serv Res. 2014 Apr 27;14:189

64. Naeim A, Henk HJ, Becker L, Chia V, Badre S, Li X, Deeter R. Pegfilgrastim prophylaxis is associated with a lower risk of hospitalization of cancer patients than filgrastim prophylaxis: a retrospective United States claims analysis of granulocyte colony-stimulating factors (G-CSF). BMC Cancer. 2013 Jan 8;13:11

65. Henk HJ, Becker L, Tan H, Yu J, Kavati A, Naeim A, Deeter R, Barron R. Comparative effectiveness of pegfilgrastim, filgrastim, and sargramostim prophylaxis for neutropenia-related hospitalization: two US retrospective claims analyses. J Med Econ. 2013;16(1):160-8. doi: 10.3111/13696998.2012.734885. Epub 2012 Oct 11.

66. Cooper KL, Madan J, Whyte S, Stevenson MD, Akehurst RL. Granulocyte colony- stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis. BMC Cancer. 2011 Sep 23;11:404

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È doveroso per me iniziare ringraziando tutte le persone che mi hanno permesso di lavorare a questa tesi: il professor Alfredo Falcone, il dottor Andrea Antonuzzo, il dottor Maurizio Lucchesi.

Desidero ringraziare inoltre la dottoressa, ma principalmente grande amica, Elisa Biasco per avermi ascoltata, sostenuta ed aiutata.

Ringrazio la mia famiglia per l’appoggio ricevuto in questi (numerosi) anni di studio,

per aver creduto sempre nelle mie capacità e avermi spronato a dare il meglio di me stessa, per avermi sostenuto anche nei momenti in cui avevo perso “la retta via”.

Ringrazio tutti i miei amici: quelli storici, conosciuti alla scuola materna ma ancora parte integrante della mia vita; le mie amiche “chèvres”, amiche dai tempi del liceo,

con le quali posso ridere e scherzare come se fossi ancora un’adolescente; gli amici incontrati all’università, con i quali si è creato un rapporto meraviglioso, tanto da considerarli parte della mia famiglia; il “gruppo Cantiere”, con il quali ho condiviso

mattine, pomeriggi e serate di studio folle ma anche tanti momenti divertenti.

Infine ringrazio me stessa per essere “tornata in carreggiata” piena di determinazione

ed aver cercato di recuperare il tempo perso, consapevole che la mia strada fosse questa.

Dedico questa tesi ai miei nonni, Antonio e Piero, che sarebbero stati fieri di me e felici di festeggiare questo traguardo. Scusate il ritardo!