Kardiotoksični efekat hemioterapije kod obolelih od nemikrocelularnog karcinoma bronha sa uznapredovalim stadijumom bolesti

Abstract

Hemioterapija koja se koristi za lečenje karcinoma utiče i na kardiovaskularni sistem. Ciljevi istraživanja su: u tvrditi uticaj kardiotoksičnosti na reživljavanje bolesnika sa uznapredovalim stadijumom NSCLC; utvrditi učestalost pojave kardiotoksičnosti kod bolesnika koji su lečeni hemioterapijom prve linije (gemcitabin/cisplatin i paclitaxel/carboplatin) sa i bez prethodnih kardiovaskularnih oboljenja i utvrditi učestalost pojave kardiotoksičnosti u toku primene protokola docetaxel/cisplatin kao hemioterapije druge linije, u odnosu na primenu protokola gemcitabin/ cisplatin i paclitaxel/carboplatin, kao terapije prve linije. Istraživanjem je obuhvaćeno 270 bolesnika sa citološki ili patohistološki dokazanim NSCLC kliničkog stadiju ma III i IV. Dobijeni su rezultati koji ukazuju da je preživljavanje bolesnika u III i IV stadijumu NSCLC koji su imali pojavu kardiotoksičnosti tokom hemioterapije prve i druge linije kraće u odnosu na bolesnike bez pojave kardiotoksičnosti, sa statističkom značajnošću nakon prvog, drugog, četvrtog ciklusa hemioterapije i nakon šest meseci (p=0.004, p=0.020, p=0.030 i p<0.0005. respektivno). Kardiotoksičnost kod bolesnika u III i IV stadijumu NSCLC koji su primali hemioterapiju prve linije prema protokolu gemcitabin/cisplatin se češće javila ukoliko su imali prethodne kardiovaskularne bolesti, ali statistička značajnost nije utvrđena. Kardiotoksičnost kod bolesnika u III i IV stadijumu NSCLC koji su primali hemioterapiju prve linije prema protokolu paclita xel/carboplatin se češće javila ukoliko su imali prethodne kardiovaskularne bolesti, a statistička značajnost utvrđena prilikom prvog kontrolnog pregleda kod bolesnika u III stadijumu (p=0.037). Kod bolesnika u III i IV stadijumu NSCLC koji su primali hemioterapiju prve linije prema protokolima gemcitabin/cisplatin paclitaxel / carboplatin kardiotoksičnost se češće javila ukoliko su imali prethodna kardiovaskularna oboljenja, ali je statistička značajnost ustanovljena samo pri prvom kontrolnom pregledu , (p=0.022). Kod bolesnika koji su primali hemioterapiju druge linije kardiotoksičnost značajno češće javila u toku prvog ciklusa hemioterapije (p=0.049) u odnosu na bolesnike koji su primali hemioterapiju prve linije. Kod bolesnika koji su imali prethodne kardiovaskularne bolesti u toku druge linije hemioterapije kardiotoksičnost se statistički značajno češće javila u odnosu na prvu liniju hemioterapije u toku četvrtog ciklusa hemioterapije (p=0.020). Uspostavljanje ravnoteže između efektivnosti hemioterapije i rizika od oštećenja kardiovaskularnog sistema zahteva blisku saradnju onkologa i kardiologa , sa ciljem kreiranja individualne terapije za svakog bolesnika.

Lung cancer chemotherapy affects the cardiovascular system as well. The research objectives were to establish: the effects of cardiotoxicity on the survival of advanced NSCLC patients; the frequency of cardiotoxicity in the patients treated with the first - line chemotherapy (gemcitabine/cisplatin and paclitaxel/carboplatin), with or without the history of cardiovascular comorbidities, and the frequency of cardiotoxicity registered in the course of the second - line chemotherapy with docetaxel/cisplatin, as compared to the first - line chemotherapy with gemcitabine/cisplatin and paclitaxel/carboplatin. The investigation included 270 patients with citologically or histopathologically confirmed NSCLC at the clinical stages III and IV. The obtained research results suggest the patients with stage III and IV NSCLC who developed cardiotoxicity in the course of the first – and second - line chemotherapy had a shorter survival than those without cardiotoxicity, with the statistical significance registered after the first, second, and fourth chemotherapy course, as well as six months later (p=0.004, p=0.020, p=0.030 and p<0.0005 respectively). Stage III and IV NSCLC patients receiving the first - line chemotherapy with gemcitabine/cisplatin developed cardiotoxicity more frequently if they had a former history of cardiovascular diseases, but with no statistical significance registered. Stage III and IV NSCLC patients on the first - line chemotherapy protocol with paclitaxel/carboplatin developed cardiotoxicity more frequently if they had a former history of cardiovascular diseases, and the statistical significance was registered at the first control examination in stage III NSCLC patients (p=0.037). Stage III and IV NSCLC patients receiving the first-line chemotherapy protocols with gemcitabine/cisplatin and paclitaxel/carboplatin developed cardiotoxicity more frequently if they had former cardiovascular diseases, but the statistical significance was registered at the first control examination only, one month after chemotherapy application (p=0.022). The patients receiving the second - line chemotherapy developed cardiotoxicity much more often during the first chemotherapy course (p=0.049), as compared to the patiens receiving the first - line chemotherapy. Among the patients with a former history of cardiovascular diseases, those receiving the second – line chemotherapy developed cardiotoxicity during the fourth chemotherapy course significanly more freequently than the patients on the same course of the first-line chemotherapy (p=0.020). To achieve the balance between chemotherapy efficacy and the risk of the cardiovascular system damage requires a close cooperation of an oncologist and a cardiologist, aimed at designing a unique, individual therapy for each patient.