Produljenje QTc intervala u bolesnica liječenih trastuzumabom i ado-trastuzumab-emtazinom

master's thesis

• Title (english): QTc prolongation induced by trastuzumab and ado-trastuzumab emtansine
• Author: Marta Begovac
• Mentor: Martina Lovrić Benčić (mentor)
• Committee member: Davor Puljević (predsjednik povjerenstva)
• Committee member: Diana Delić-Brkljačić (član povjerenstva)
• Committee member: Martina Lovrić Benčić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Internal Medicine); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Internal Medicine
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Pharmacology and Toxicology

Abstract

Trastuzumab i trastuzumab emtazin su lijekovi koji se koriste za liječenje bolesnica s HER 2 pozitivnim karcinomom dojke. Trastuzumab je monoklonsko protutijelo za humani epidermalni čimbenik rasta receptora 2 (HER2), a trastuzumab emtazin je konjugat trastuzumaba i emtazina. Njihove moguće nuspojave su produljenje QT intervala i smanjenje ejekcijske frakcije lijevog ventrikula (LVEF). Cilj ovog istraživanja bio je ispitati njihov učinak na produljenje QTc intervala. ----- METODE: Sve bolesnice su prethodno liječene standardnom kombinacijom paklitaksela i cisplatine. Nakon toga su liječene trastuzumabom, a zatim trastuzumab emtazinom. Ukupno 26 bolesnica koje su imale očuvanu LVEF liječeno je trastuzumabom, a prije svake primjene lijeka sniman je i analiziran EKG. Zbog pada LVEF-a dvije bolesnice su prestale s liječenjem. 24 bolesnice nastavilo je liječenje s trastuzumab emtazinom zbog metastaske bolesti. Posljednji EKG zapisi snimljeni su 6 mjeseci nakon zadnje primjene lijekova. ----- REZULTATI: Utjecaj oba lijeka na PQ interval i QRS kompleks nije uočen. Značajno produljenje QTc intervala primijećeno je nakon treće primjene oba lijeka i nastavljeno je tijekom četvrte, pete i šeste primjene oba lijeka. Normalizacija QTc intervala primijećena je nakon šest mjeseci bez terapije. ----- ZAKLJUČAK: Liječenje trastuzumabom i trastuzumab emtanzinom značajno produljuje QTc interval u bolesnica s HER2 pozitivnim karcinomom dojke, ali je taj učinak reverzibilan.

Abstract (english)

Trastuzumab and trastuzumab emtansine are drugs used to treat HER2-positive breast cancer. Trastusumab is a specific antibody for human epidermal growth factor receptor 2 (HER2) and trastusumab emtasine is an antibody-drug conjugate. Their potential side effects include QT prolongation and reduction of left ventricular ejection fraction. The aim of this study was to determine their effect on the QTc interval. ----- METHODS: All patients were previously treated with standard paclitaxel and cisplatin based regimens. After regimens they received trastusumab and afterwards trastusumab emtasine. 26 patients with preserved LVEF were treated with trastuzumab. Before every application ECG was obtained and examined. Due to reduction of LVEF, two patiens were excluded from treatment. 24 patients with metastatic disease continued treatment with trastusumab emtansine protocol. The final ECG was obtained 6 months after the last drug application. ----- RESULTS: Trastusumab and trastusumab emtasine showed no effect on PQ and QRS intervals. Statistically significant QT prolongation was found after the third drug application and it continued with every successive application, reaching peak QT values before the fifth cycle. This effect was reversible and QT interval returned to its initial values 6 months after the last drug application. ----- CONCLUSION: Trastusumab and trastuzumab emtansine significantly prolong QTc interval in patients with HER 2 positive breast cancer but this effect is reversible.

• Keywords: HER2 pozitivni karcinom dojke; QTc interval; trastuzumab; ado-trastuzumab-emtazin
• Keywords (english): HER2-positive breast cancer; QTc interval; trastusumab; ado-trastusumab-emtasine
• Language: croatian
• URN:NBN: urn:nbn:hr:105:665453
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Public note: Pohranitelj objekta unio ključne riječi.
• Created on: 2020-06-10 10:29:16