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Faoro, Sonia (2016) Eventi endocrini correlati alla somministrazione di farmaci antitumorali. [Tesi di dottorato]

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Abstract (inglese)

This thesis highlights how the observational study of adverse events (in this case endocrine related) in oncology and, in general, clinical medicine can offer ideas for scientific research.
We focused our attention on the study of secondary endocrine effects of anti-tumor drugs because, as shown by the recent literature, with new targeted therapies, the classic acute toxicities of cytotoxic chemotherapy (vomiting, diarrhea, hair loss etc.) have decreased but less obvious toxicities, which are sometimes more subtle, such as those related to the endocrine system, have emerged.
The unusual event of a rare endocrine disease, such as autoimmune hypophysitis, becoming a relatively common adverse event following a treatment with an anticancer drug (ipilimumab), provides the opportunity to study the rare disease itself.
It is less unusual, however, that the study of a drug-related toxicity in a subset of patients (who respond best to therapy) may suggest a relationship between the target receptor and the adverse event at the molecular level (hypothyroidism-induced sunitinib).
It also seems that the pharmacological treatment (zoledronic acid) of an adverse event (osteoporosis) caused by a class of anticancer agents (aromatase inhibitors) may improve survival outcomes of the malignant disease.
This thesis shows that active surveillance of adverse events can make an important contribution not only to clinical but also to translational research.
It is confirmed, therefore, that pharmacovigilance is an essential activity for the improvement of patient care.

Abstract (italiano)

In questa tesi si vuole evidenziare come lo studio osservazionale di eventi avversi (nel nostro caso quelli di tipo endocrino) in ambito oncologico e clinico in generale, possa offrire degli spunti per la ricerca scientifica.
Ci siamo orientati verso lo studio di effetti endocrini secondari alla somministrazione di farmaci antumorali perché, come si evince dalla recente letteratura, con le nuove terapie a bersaglio molecolare sono diminuite le classiche tossicità di tipo acuto delle terapie citotossiche (vomito, diarrea, perdita di capelli ecc) ma sono emerse tossicità meno evidenti e per questo qualche volta più subdole come quelle di tipo endocrino.
E’ insolito che una patologia endocrina rara, come l’ipofisite autoimmune, diventi un evento avverso relativamente frequente a seguito di una cura con un farmaco antitumorale (ipilimumab), fornendo, quindi, anche l’occasione per lo studio della patologia rara stessa.
E’ meno insolito, invece, che lo studio di una tossicità farmaco-correlata in un sottogruppo di pazienti (che rispondono meglio alla terapia), possa suggerire una relazione tra il recettore bersaglio e l'evento avverso stesso a livello molecolare (ipotiroidismo indotto da sunitinib).
Ma sembra anche che il trattamento farmacologico (acido zoledronico) di un evento avverso (osteoporosi) causato da una classe di farmaci antitumorali (inibitori dell’aromatasi) possa indurre miglioramenti sugli outcome di sopravvivenza della patologia tumorale.
Dalla presente tesi emerge che la sorveglianza attiva degli eventi avversi può dare un importante contributo non solo alla ricerca clinica ma anche a quella traslazionale.
Si conferma, pertanto, che la farmacovigilanza è un’attività essenziale per il miglioramento della cura del paziente

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Tipo di EPrint:Tesi di dottorato
Relatore:Opocher , Giuseppe
Correlatore:Zovato, Stefania
Dottorato (corsi e scuole):Ciclo 28 > Scuole 28 > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > METODOLOGIA CLINICA, SCIENZE ENDOCRINOLOGICHE, DIABETOLOGICHE E NEFROLOGICHE
Data di deposito della tesi:24 Aprile 2016
Anno di Pubblicazione:24 Aprile 2016
Parole chiave (italiano / inglese):Eventi avversi endocrini, farmacovigilanza attiva, inibitori dell’aromatasi, inibitori della tirosinkinasi, anti-CTLA-4 Endocrine adverse effects, active drug surveillance, aromatase inhibitor, tyrosine kinase inhibitor, anti-CTLA-4
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/13 Endocrinologia
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina
Codice ID:9625
Depositato il:06 Ott 2016 16:45
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