Sigurnosni profil inhibitora kinaze anaplastičnog limfoma odobrenih u liječenju karcinoma pluća ne-malih stanica

master's thesis

• Title (english): Adverse drug reactions of anaplastic lymphoma kinase inhibitors approved for treatment of non-small cell lung cancer
• Author: Andrea Budeš
• Mentor: Lidija Bach-Rojecky (mentor)
• Mentor: Nikica Mirošević Skvrce (mentor)
• Committee member: Lidija Bach-Rojecky (predsjednik povjerenstva)
• Committee member: Maja Ortner Hadžiabdić (član povjerenstva)
• Committee member: Nikica Mirošević Skvrce (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmacology); Zagreb
• Defense date and country: 2021, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Identifikacija onkogene aktivacije specifičnih tirozin-kinaznih receptora u molekularnoj patogenezi uznapredovalog stadija karcinoma pluća ne-malih stanica (NSCLC), posebice fuzijska mutacija gena za kinazu anaplastičnog limfoma (ALK), dovela je do moderniziranog pristupa liječenju temeljenog na molekularno ciljanoj terapiji. Cilj ovog diplomskog rada bio je analizirati neželjene reakcije ALK inhibitora odobrenih u indikaciji karcinoma pluća ne-malih stanica koje je Hrvatska agencija za lijekove i medicinske proizvode zaprimila u razdoblju od 2013. do 31. svibnja 2020. godine. Prijavljeni slučajevi nuspojava ALK inhibitora analizirani su prema sljedećim kriterijima: ukupni broj slučajeva, dob, spol, lijek tj. ALK inhibitor, kvalifikacija prijavitelja nuspojave, pripadnost nuspojave s obzirom na klasifikaciju organskih sustava (SOC) i klasifikaciju preferiranih pojmova (PT) prema MedDRA sistematizaciji, ozbiljnost nuspojave i istovremena primjena s drugim lijekovima. HALMED je zaprimio ukupno 13 prijava sumnji na nuspojavu. Najveći broj pacijenata odnosio se na pacijente ženskog spola te na dobnu skupinu od 45. do 64. godine. Krizotinib je ALK inhibitor s najviše prijavljenih nuspojava. Prema SOC klasifikaciji, Pretrage su uključivale najveći broj neželjenih reakcija, dok je prema PT klasifikaciji progresija bolesti zauzimala najveći udio prijavljenih nuspojava. Pet od trinaest nuspojava bilo je kategorizirano pod ozbiljne nuspojave, a u dva je slučaja bila potrebna hospitalizacija ili produljenje hospitalizacije. Niti jedna nuspojava rezultirala smrtnim ishodom te nisu zabilježene interakcije s drugim lijekovima. Stečena saznanja o nuspojavama ove važne skupine lijekova omogućavaju prevenciju i adekvatnu intervenciju u slučaju njihove manifestacije tokom liječenja karcinoma pluća.

Abstract (english)

The identification of oncogenic activation of specific receptor tyrosine-kinases in terms of molecular pathogenesis of non-small cell lung cancer (NSCLC), especially the rearrangements of the anaplastic lymphoma kinase (ALK) gene has led to a paradigm shift and the development of a new modernistic concept of specific molecular treatments for patients. The aim of this study was to describe adverse drug reactions (ADRs) of tyrosine kinase inhibitors (TKIs) approved for the treatment of NSCLC. The ADRs were reported to the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) between 2013 and May 31st 2020. Data were analyzed in respect of the total number of reports, demographic characteristics of the patients, suspected drug, reporter, MedDRA system Organ Classes and Preffered Terms, seriousness of ADRs and suspected/interacting active compounds. HALMED received a total of 13 reports related to NSCLC ALK inhibitors. Most of the patients were female and belonged to the 45-64 age group. The highest number of adverse reactions were reported for the use of crizotinib. Most ADRs belonged to the System Organ Class Investigations and the most reported MedDRA Preferred Term was disease progression. Five out of thirteen ADRs were reported as serious and caused or prolonged hospitalization. None of the reported ADRs had a fatal outcome and there were no reported interacting drugs. The acquired knowledge about ADRs of ALK TKIs enables prevention and adequate intervention in case of their manifestation during the cancer treatment.

• Keywords: karcinom pluća ne-malih stanica; NSCLC; kinaza anaplastičnog limfoma; ALK; ALK inhibitori; nuspojave lijekova
• Keywords (english): non-small cell lung cancer; NSCLC; anaplastic lymphoma kinase; ALK; ALK inhibitors; adverse drug reactions
• Language: croatian
• URN:NBN: urn:nbn:hr:163:566371
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-04-26 14:50:30