The effects of CDK4 inhibitors on the quality of life and palpitations in patients with metastatic breast cancer

Karcinom dojke jedna je od najčešćih malignih bolesti koja pogađa brojne žene diljem svijeta. U slučaju uznapredovanog ER+, PR+/ HER 2- karcinoma dojke prva linija terapije je CDK 4 inhibitor u kombinaciji s endokrinom terapijom. Endokrina terapija je standardni protokol liječenja već dugi niz godina, te su poznati mehanizam djelovanja i moguće nuspojave. S druge strane, lijekovi palbociklib, ribociklib i abemaciklib su tek nedavno odobreni za kliničku praksu. Uz češće zabilježene nuspojave CDK 4 inhibitora kao što su mučnina, gubitak apetita, povraćanje, umor, anemija, neutropenija i sl. sve učestalija nuspojava liječenja karcinoma dojke je i kardiotoksičnost. Kardiotoksičnost negativno djeluje na KV prognozu i ograničava terapeutske mogućnosti onkološkog liječenja. Produljenje QT intervala posebno je povezano s ribociklibom te je ovisno o primljenoj dozi i može uzrokovati smrtonosnu aritmiju torsades de pointes. Aritmija se može klinički očitovati neugodnim osjećajem rada srca, odnosno palpitacijama. Pravovremeno prepoznavanje i liječenje kardiotoksičnosti poboljšava prognozu i kvalitetu života. Druge nuspojave su također bitan faktor koji utječe na kvalitetu života. PALOMA – 2 i – 3 studija te podaci iz kliničkog života su pokazali da je skala boli niža u pacijentica koje su u terapiji imale CDK 4 inhibitor s endokrinom terapijom u odnosu na endokrino liječenje uz placebo. Nadalje, pacijentice su za vrijeme terapije CDK 4 inhibitorom svoju kvalitetu života opisivale kao dobru i zadovoljavajuću. CDK4 inhibitori ispitani su u raznim studijama i uočeno je da produljuju vrijeme bez progresije bolesti. Jednako važno ako ne i važnije od toga je činjenica da se ovi lijekovi dobro podnose te da pacijenti imaju održanu kvalitetu života. Utjecaj CDK 4 inhibitora na produljenje QT intervala i osjećaj palpitacija te mehanizam kojim djeluje na navedeno još se detaljno treba istražiti.Breast cancer is one of the most common malignancies affecting many women around the world. In the case of advanced ER+, PR+/ HER2- breast cancer, the first line of treatment is a CDK 4 inhibitor in combination with endocrine therapy. Endocrine therapy has been the standard protocol for many years, and the mechanism of action and side effects of these drugs are widely known. On the other hand, the drugs, palbociclib, ribociclib, and abemaciclib, have only recently been approved for clinical practice. In addition to the more commonly reported CDK 4 inhibitors side effects such as nausea, loss of appetite, vomiting, fatigue, anaemia, neutropenia, etc., they also cause more severe side effects such as cardiotoxicity. Cardiotoxicity negatively affects the CV prognosis and limits the therapeutic possibilities of oncological treatment. QT prolongation is particularly associated with ribociclib and is dose-dependent and can cause fatal TdP. The arrhythmia may clinically manifest as palpitations, an uncomfortable feeling of heartbeat. Recognition and treatment of cardiotoxicity early on improves prognosis and quality of life. Other side effects are an important factor that further affects the quality of life. PALOMA - 2 and - 3 studies and real-world data showed that the pain scale was lower in patients treated with CDK 4 inhibitors with endocrine therapy compared to endocrine treatment with placebo. They also described their quality of life during CDK 4 inhibitor therapy as good and satisfactory. In addition, CDK4 inhibitors have been studied in various studies and have been observed to prolong progression-free survival. Equally important, if not more important than this, is the fact that these drugs are well tolerated and that patients have a maintained quality of life. The influence of CDK 4 inhibitors on QT prolongation and the sensation of palpitations and the mechanism by which it acts on the above need to be further investigated