Hepatotoksičnost citotoksične kombinovane hemioterapije sa biološkom terapijom ili bez nje kod bolesnika sa metastatskim kolorektalnim karcinomom

Abstract

Kolorektalni karcinom (CRC) je jedno od najčešćih malignih oboljenja. U trenutku dijagnostikovanja kod većine obolelih se detektuju metastaze na jetri. Zbog toga je pravovremena upotreba hemioterapeutika za njihovo lečenje od velikog značaja. Tretman metastatskog kolorektalnog karcinoma se zasniva na kombinovanoj upotrebi konvencionalnih citostatika i monoklonskih antitela kao što je npr. bevacizumab. Konvencionalni citostatski protokoli lečenja ispoljavaju neželjene efekte na tkivo jetre. Hepatotoksični efekti hemioterapije se manifestuju u vidu poremećaja vrednosti biohemijskih parametara funkcionalnog statusa jetre. Dodatak bevacizumaba konvencionalnim citostaticima poboljšava njihov terapijski efekat, dok je njegov uticaj na prouzrokovani poremećaj vrednosti biohemijskih parametara nepoznat. Takođe, nije poznata korelacija postignutog kliničkog odgovora sa narušenim vrednostima biohemijskih parametara. Shodno tome, primarni cilj našeg istraživanja je bio komparativna analiza vrednosti biohemijskih parametara funkcije jetre bolesnika lečenih konvencionalnim citostaticima sa vrednostima parametara bolesnika dodatno tretiranih bevacizumabom. Kao sekundarni, ne manje važan cilj, je bio utvrđivanje odnosa kliničkih ishoda bolesnika sa vrednostima biohemijskih parametara jetre. U studiju je uključeno 96 bolesnika obololelih od CRC sa histološki potvrđenim, neresektabilnim metastazama na jetri zbog kojih do trenutka uključivanja u studiju nisu tretirani hemioterapijskim protokolom. Bolesnici koji su prethodno, radi primarnog CRC lečeni određenim hemioterapijskim ili radioterapijskim protokolom su uključeni u studiju samo ukoliko je sprovedeni terapijski protokol završen najmanje mesec dana pre početka studije. Bolesnicima je na osnovu odluke ordinirajućeg onkologa dodeljen FOLFOX4 ili FOLFOX4+Bevacizumab hemioterapijski protokol kao terapijski protokol prve linije. Bolesnici su grupisani na osnovu hemioterapijskog protokola koji su primali...

Colorectal carcinoma (CRC) is one the most frequently malignant disease with early liver metastasis. This requires timely use of anticancer drugs. Current treatment of metastatic CRC consists of combined usage of conventional anticancer drugs with the addition of monoclonal antibodies, e.g. bevacizumab. Conventional treatment protocols exert undesired effects on liver tissue which are manifested as a disturbance of liver function tests parameters. The addition of bevacizumab improves their therapeutic effect, but its influence on caused biochemical disturbances is not completely known. Also, the relation between clinical outcome and disorder of biochemical parameters has not been completely evaluated. Therefore the primary objective of our study was comparative analysis of liver function tests parameters in patients treated with conventional anticancer drugs with those additionally treated with bevacizumab. Secondary, but not less important objective was to examine whether clinical outcome in this way treated patients, correlates with the level of liver function tests parameters or not. The study included 96 patients with histologically confirmed and previously untreated liver metastatic CRC, without possibility for curative liver resection. Prior used chemotherapy and radiotherapy for CRC treatment was allowed if they were completed the treatment at least one month before patient inclusion in the study. Patients were assigned to FOLFOX4 or FOLFOX4+Bevacizumab as first line treatment protocol according to physician decision. According to treatment protocol they were assigned, the patients were divided in two groups, one group (n=44) was treated with FOLFOX4 (group 1), and the other one (n=52) with bevacizumab added to FOLFOX4 treatment protocol (group 2). Depending on the response of patients, the duration of treatment varied from 2 to 6 months. Treatment was conducted at the Institute for Radiology and Oncology in Belgrade, Serbia. Demographic and clinical data were obtained by reviewing medical records for period from January 2009 to December 2014. The study was carried out in accordance with the Declaration of Helsinki, Good Clinical Practice Guidelines and institutional ethics committee requirements. All patients gave written informed consent before study participation...