Influence of HER-2/neu gene polymorphism on monoclonal antibody trastuzumab induced cardiotoxicity

Malobrojna dosadašnja istraživanja pokazala su dvojbene rezultate utjecaja polimorfizma gena HER-2/neu na kardiotoksičnost uzrokovanu monoklonskim protutijelom trastuzumabom. Obzirom na izuzetno važan biljeg u onkologiji i mogući čimbenik rizika srčanog oštećenja, nametnula se potreba ovakvog istraživanja. U istraživanje su uključene ispitanice adjuvantno liječene trastuzumabom zbog HER2 pozitivnog ranog raka dojke (n=177). Ispitanice su podijeljenje u dvije grupe: grupa A (n=99) kod kojih nije došlo do kardiotoksičnosti tijekom liječenja trastuzumabom i grupa B (n=78) kod kojih je došlo do razvoja kardiotoksičnosti. Istraženi su rizični čimbenici kao i osobitosti same kardiotoksičnosti, vrijeme pojavnosti i oporavka te reverzibilnost. Svim ispitanicama je lančanom reakcijom polimeraze određen polimorfizam gena HER-2/neu na kodonu 655 [Ile655Val] te distribucija genotipa Ile/Val, Ile/Ile i Val/Val. Praćenje srčane funkcije ehokardiografijom bilo je u skladu s usvojenim smjernicama praćenja. Iz rezultata dobivenih usporedbom grupa A i B nije nađena povezanost između pojedinog genotipa HER-2/neu i pojave kardiotoksičnosti.A few studies so far have shown doubtful results on influence of HER-2/ neu gene polymorphism on cardiotoxicity caused by monoclonal antibody trastuzumab. Remarkable importance of this marker in oncology and its place as a possible risk factor for cardial damage, imposed the need for this kind of research. The study included patients adjuvantly treated with trastuzumab for HER2 positive breast cancer (n = 177). Subjects were divided into two groups: group A (n = 99), which did not experience cardiotoxicity during treatment with trastuzumab and group B (n = 78) which did. Risk factors were investigated as well as the characteristics of cardiotoxicity, time of occurrence and recovery, and reversibility. Polymorphism of the HER-2/ neu gene on codon 655 [Ile655Val] and Ile/Val, Ile/Ile and Val/Val genotype distribution was determined by polimerase chain reaction in all patients. Heart function monitoring with echocardiography was consistent with the adopted monitoring guidelines. From the results obtained by comparing groups A and B, no correlation was found between HER-2/neu genotype and cardiotoxicity

HER2 pozitivni karcinom dojke u starijih bolesnica: biologija tumora i specifičnosti sistemskog liječenja

Breast cancer is the most common cancer in females and it is primarily disease of ageing with highest incidence in women older than 65 years. There are statistically signifi cant diff erences in breast cancer histology considering patients age and older patients are usually diagnosed with larger, hormone sensitive tumors. Approximately 15-25% of all women diagnosed with early breast cancer have tumor overexpressing HER2/neu receptor. A golden standard for early and metastatic HER2 positive breast cancer treatment is trastuzumab. Studies in adjuvant sett ing showed that one year of trastuzumab therapy reduces the risk of death by one-third. Important side eff ect of trastuzumab treatment is cardiotoxicity, whose precise mechasnisms are not clear yet. The aim of our study was to determine diff erences in biological characteristics of tumor, treatment options and cardiac side eff ects in elderly patients with HER2 positive early breast cancer. Research included patients with early, histologically confi rmed, HER2 positive breast cancer who underwent prior breast surgery and axillary node dissection. Patients were divided into two groups considering age: group I ≤ 65 years of age and group II > 65 years of age. Patients received adjuvant anthracycline or non-antracycline based chemotherapy followed by one year of trastuzumab monotherapy. Cardiac function was monitored with echocardiography by measuring left ventricle ejection fraction (LVEF) in patients before starting trastuzumab, 3 months and 8 months after trastuzumab was introduced. Incidence of trastuzumab induced cardiac dysfunction showed no signifi cant difference between younger and older patients except in group of older patients with cardiovascular risk who had signifi cantly higher incidence of cardiac dysfunction.Karcinom dojke je najčešći karcinom u žena i primarno je bolest starenja s najvećom incidencijom u žena dobi iznad 65 godina. Postoje statistički značajne razlike u histologiji karcinoma dojke obzirom na dob bolesnice i starije bolesnice obično imaju veći, hormonski ovisan tumor. 15-25% svih žena kojima se dijagnosticira rani karcinom dojke imaju tumor koji pretjerano eksprimira HER2/neu receptor. Zlatni standard za liječenje ranog i uznapredovalog HER2 pozitivnog karcinoma dojke je trastuzumab. Studije u adjuvantnom liječenju su pokazale da jednogodišnje terapija trastuzumabom smanjuje rizik od smrti za jednu trećinu. Važna nuspojava liječenja trastuzumabom je kardiotoksičnost, čiji mehanizmi nastanka još nisu potpuno razjašnjeni. Cilj našeg istraživanja je bio utvrditi razlike u biološkim karakteristikama tumora, terapijskim opcijama i kardijalnim nuspojavama u starijih bolesnica s ranim HER2 pozitivnim tumorom dojke. U istraživanje smo uključili bolesnice s ranim, histološki potvrđenim, HER2 pozitivnim karcinomom dojke koje su ranije liječene kiruški, operacijom dojke i odstranjenjem aksilarnih limfnih čvorova. Bolesnice su podijeljene u dvije skupine obzirom na dob: grupa I – mlađe od 65 godina i grupa II – starije od 65 godina. Bolesnice su primile adjuvantnu kemoterapiju na bazi antraciklina ili protokolom bez antraciklinskog preparata nakon čega je slijedilo liječenje trastuzumabom u monoterapiji kroz godinu dana. Srčana funkcija je praćena uz pomoć ehokardiografije, mjerenjem ejekcijske frakcije lijevog ventrikla prije početka terapije trastuzumabom te 3 i 8 mjeseci nakon početka terapije trastuzumabom. Incidencija trastuzumabom inducirane kardiotoksičnosti nije pokazala statistički značajnu razliku između mlađih i starijih bolesnica, osim u grupi starijih bolesnica sa kardiovaskularnim rizikom, koje su imale značajno veću incidenciju srčanog popuštanja

Vrijeme primjene trastuzumaba i rizik za razvoj srčane disfunkcije u bolesnica sa ranim HER2 pozitivnim karcinomom dojke

Breast cancer is the most common malignant tumor in females in the world. Age is signifi cant risk factor and incidence increases rapidly after age of 35. Approximately one fourth of patients with breast cancer have tumors that overexpress HER2 protein or amplify the HER2/neu gene.Trastuzumab is a recombinant humanized monoclonal antibody that binds to a specific extracellular growth factor, human epidermal growth factor type 2 HER 2-neu or ErbB2, tyrosine kinase receptor responsible for alterations in cellular metabolism and growth.Clinical studies have shown that trastuzumab given concurrently or following adjuvant chemotherapy improves disease-free survival (DFS) and overal survival (OS) in early-stage HER-2 positive breast cancer. HERA study (Herceptin in Adjuvant breast cancer) showed that one of fifty women treated with trastuzumab adjuvantly developes congestive heart failure during treatment.Mechanisms of trastuzumab induced cardiac dysfunction are not clear yet. Studies have shown that differences in timing of trastuzumab after chemotherapy an ddifferences in total dose of anthracyclines can explain differences in incidence of cardiac dysfunction. The aim of our study was to determine incidence of trastuzumab induced cardiac dysfunction in patients with HER2 positive early breast cancer and impact of time interval between administration of chemotherapy and trastuzumab on prevalence of cardiac dysfunction. Follow up included 140 patients with early HER2 positive breast cancer treated with trastuzumab adjuvantly. Seventeen patients developed symptomatic cardiac dysfunction (12.1%) of which 6 developed severe congestive heart failure NYHA III/IV(4.2%) and 11 moderate NYHA II/III (7.9%).Patients who started trastuzumab therapy 11 to 20 days after finishing chemotherapy had 11% incidence of symptomatic heart failure, same as those patients who started trastuzumab 26 to 35 days after chemotherapy. There were no cardiac events if treatment was started 35 days after chemotherapy. Highest incidence of congestive heart failure was registered when trastuzumab was applied 21 to 25 days after adjuvant chemotherapy (22%). Time interval between cessation of adjuvant chemotherapy and fi rst trastuzumab application has a signifi cant impact on prevalence of trastuzumab induced cardiac dysfunction.Karcinom je najčešći maligni tumor u žena u svijetu. Dob je značajan rizični faktor i incidencija se povećava iznad dobi od 35 godina. Otprilike četvrtina bolesnica oboljelih od raka dojke ima tumor koji prekomjerno izražava HER2. Trastuzumab je rekombinantno humanizirano monoklonalno protutijelo koje se veže na humani epidermalni faktor rasta tip 2 HER2-neu ili ErbB2, tirozin kinazni receptor odgovoran za promjene u metabolizmu i rastu stanice. Kliničke studije su pokazale da davanje trastuzumaba konkomitantno s ili nakon adjuvantne kemoterapije produžuje period bez povrata bolesti (DSF) i ukupno preživljenje (OS) u ranog HER2 pozitivnog karcinoma dojke. Studija HERA (Herceptin in Adjuvant Breast Cancer) je pokazala da jedna od pedeset žena liječenih trastuzumabom adjuvantno, razvija kongestivno zatajenje srca tijekom liječenja. Mehanizmi nastanka trastuzumabom inducirane kardiotoksičnosti još nisu potpuno razjašnjeni. Studije su pokazale da razlike u vremenu započimanja terapije trastuzumabom nakon završene adjuvantne kemoterapije i razlike u ukupnoj dozi antraciklina mogu objasniti razlike u incidenciji srčanog zatajenja. Cilj našeg istraživanja je bio odrediti incidenciju trastuzumabom inducirane kardiotoksičnosti u bolesnica s ranim HER2 pozitivnim karcinomom dojke te odrediti utjecaj vremenskog intervala od završetka kemoterapije do početka liječenja trastuzumabom na pojavnost srčanog zatajenja. Praćenje je uključilo 140 bolesnica s ranim HER2 pozitivnim karcinomom dojke koje su liječenje trastuzumabom adjuvantno. 17 bolesnica je razvilo simptomatsko srčano zatajenje (12.1%) od kojih 6 teškog stupnja NYHA III/IV(4.2%) a 11 umjerenog NYHA II/III (7.9%).Bolesnice koje su započele liječenje trastuzumabom 11 do 20 dana po završetku kemoterapije su imale incidenciju simptomatskog srčanog zatajenja 11%, kao i bolesnice koje su započele terapiju trastuzumabom 26 do 35 dana nakon kemoterapije. U bolesnica koje su liječenje započele 35 dana nakon kemoterapije nije zabilježeno kardijalnih događanja. Najviša incidencija kongestivnog zatajenja srca je zabilježena kada je terapija trastuzumabom započeta 21 do 25 dana nakon adjuvantne kemoterapije (22%). Vremenski interval između završetka adjuvantne kemoterapije i prve aplikacije trastuzumaba ima značajan utjecaj na pojavnost trastuzumabom induciranog srčanog zatajenja

Utjecaj sastava tijela na kvalitetu života premenopauzalnih bolesnica s ranim stadijem raka dojke tijekom kemoterapije

Body composition has been studied relatively recently as part of oncology trials in different types of tumors. There are numerous studies that define the impact of chemotherapy side effects on the quality of life (QoL) of breast cancer patients, however, there are few studies that analyze the impact of body composition on the QoL of premenopausal patients in the course of cytotoxic treatment. The study was performed on a sample of premenopausal patients treated with neoadjuvant or adjuvant AC chemotherapy for early-stage breast cancer at Day Hospital of the Department of Medical Oncology, University Hospital for Tumors in Zagreb. The study included 68 patients, median age 46.6 years. Analysis of the QoL questionnaires and their association with body composition indicated several interesting results. At the beginning of treatment, most pronounced was the connection between body composition and physical and sexual functioning and hair loss, while in subsequent treatment cycles the effect on other QoL subdomains, in particular fatigue and diarrhea, was more pronounced. In conclusion, we found body composition to have a significant impact on certain QoL subdomains during treatment.Sastav tijela se počeo proučavati relativno nedavno u sklopu onkoloških ispitivanja u različitim vrstama tumora. Postoje brojne studije koje definiraju utjecaj nuspojava kemoterapije na kvalitetu života bolesnika oboljelih od raka dojke, međutim, malo je studija koje su analizirale utjecaj sastava tijela na kvalitetu života premenopauzalnih bolesnica tijekom citotoksičnog liječenja. Studija je provedena na uzorku premenopauzalnih bolesnica liječenih neoadjuvantnom ili adjuvantnom kemoterapijom po protokolu AC za rani stadij raka dojke u Dnevnoj bolnici Zavoda za internističku onkologiju Klinike za tumore u Zagrebu. U istraživanju je sudjelovalo 68 bolesnica, medijan dobi od 52,6 godina. Analiza upitnika kvalitete života i njihova povezanost sa sastavom tijela ukazali su na nekoliko zanimljivih rezultata. Na početku liječenja najizraženija je bila veza između sastava tijela i fizičkog i seksualnog funkcioniranja te gubitka kose, dok je u kasnijim ciklusima liječenja utjecaj na druge poddomene kvalitete života, osobito umor i proljev, bio više izražen. Zaključno, sastav tijela ima značajan utjecaj na određene poddomene kvalitete života u tijeku kemoterapijskog liječenja

Sustavno antineoplastično liječenje raka dojke

Breast cancer is the most common cancer in women. Early breast cancer is potentially curable disease. Systemic adjuvant therapy is created to treat micrometastatic disease or destroy breast cancer cells that have spread from the breast and regional lymph nodes, but have not yet formed visible distant metastases. Systemic adjuvant therapy is based on chemotherapy with or without targeted therapy, and endocrine therapy, sometimes in combination with adjuvant irradiation, usually is conducted after surgery. The aim of adjuvant therapy is to decrease recurrence rate and extension of overall survivalRak dojke najčešća je zloćudna bolest u žena, potencijalno izlječiva u ranom stadiju. Sustavno adjuvantno liječenje osmišljeno je za uništenje mogućih mikrometastaza proširenih iz dojke i/ili iz regionalnih limfnih čvorova, koje još nisu stvorile vidljive udaljene metastaze. Temelji se na kemoterapiji sa ili bez ciljane biološke terapije, na endokrinoj terapiji, ponekad u kombinaciji sa zračenjem, obično nakon kirurškog zahvata. Cilj je smanjiti stopu povratka bolesti i produžiti život bolesnika

Sustavno antineoplastično liječenje metastatskog raka dojke

Systemic therapy of metastatic breast cancer is not curative and its goal is life prolongation and improvement of quality of life. Treatment of metastatic breast cancer usually involvesendocrine therapy and/or chemotherapy with or without targeted therapy. The use of the minimally toxic endocrine therapies is preff ered to the use of cytotoxic therapy whenever reasonable.Sustavno liječenje metastatskog raka dojke nije kurativno već se provodi u svrhu produženja života i poboljšanja kvalitete života. Sustavno liječenje se sastoji od endokrine terapije i/ili kemoterapije uz ili bez primjene ciljane biološke terapije. U liječenju metastatskog raka dojke preferirani oblici liječenja su oni najmanje toksični te se endokrina terapija primjenjuje kad god je to moguće

HER2 pozitivni karcinom dojke u starijih bolesnica: biologija tumora i specifičnosti sistemskog liječenja

Breast cancer is the most common cancer in females and it is primarily disease of ageing with highest incidence in women older than 65 years. There are statistically signifi cant diff erences in breast cancer histology considering patients age and older patients are usually diagnosed with larger, hormone sensitive tumors. Approximately 15-25% of all women diagnosed with early breast cancer have tumor overexpressing HER2/neu receptor. A golden standard for early and metastatic HER2 positive breast cancer treatment is trastuzumab. Studies in adjuvant sett ing showed that one year of trastuzumab therapy reduces the risk of death by one-third. Important side eff ect of trastuzumab treatment is cardiotoxicity, whose precise mechasnisms are not clear yet. The aim of our study was to determine diff erences in biological characteristics of tumor, treatment options and cardiac side eff ects in elderly patients with HER2 positive early breast cancer. Research included patients with early, histologically confi rmed, HER2 positive breast cancer who underwent prior breast surgery and axillary node dissection. Patients were divided into two groups considering age: group I ≤ 65 years of age and group II > 65 years of age. Patients received adjuvant anthracycline or non-antracycline based chemotherapy followed by one year of trastuzumab monotherapy. Cardiac function was monitored with echocardiography by measuring left ventricle ejection fraction (LVEF) in patients before starting trastuzumab, 3 months and 8 months after trastuzumab was introduced. Incidence of trastuzumab induced cardiac dysfunction showed no signifi cant difference between younger and older patients except in group of older patients with cardiovascular risk who had signifi cantly higher incidence of cardiac dysfunction.Karcinom dojke je najčešći karcinom u žena i primarno je bolest starenja s najvećom incidencijom u žena dobi iznad 65 godina. Postoje statistički značajne razlike u histologiji karcinoma dojke obzirom na dob bolesnice i starije bolesnice obično imaju veći, hormonski ovisan tumor. 15-25% svih žena kojima se dijagnosticira rani karcinom dojke imaju tumor koji pretjerano eksprimira HER2/neu receptor. Zlatni standard za liječenje ranog i uznapredovalog HER2 pozitivnog karcinoma dojke je trastuzumab. Studije u adjuvantnom liječenju su pokazale da jednogodišnje terapija trastuzumabom smanjuje rizik od smrti za jednu trećinu. Važna nuspojava liječenja trastuzumabom je kardiotoksičnost, čiji mehanizmi nastanka još nisu potpuno razjašnjeni. Cilj našeg istraživanja je bio utvrditi razlike u biološkim karakteristikama tumora, terapijskim opcijama i kardijalnim nuspojavama u starijih bolesnica s ranim HER2 pozitivnim tumorom dojke. U istraživanje smo uključili bolesnice s ranim, histološki potvrđenim, HER2 pozitivnim karcinomom dojke koje su ranije liječene kiruški, operacijom dojke i odstranjenjem aksilarnih limfnih čvorova. Bolesnice su podijeljene u dvije skupine obzirom na dob: grupa I – mlađe od 65 godina i grupa II – starije od 65 godina. Bolesnice su primile adjuvantnu kemoterapiju na bazi antraciklina ili protokolom bez antraciklinskog preparata nakon čega je slijedilo liječenje trastuzumabom u monoterapiji kroz godinu dana. Srčana funkcija je praćena uz pomoć ehokardiografije, mjerenjem ejekcijske frakcije lijevog ventrikla prije početka terapije trastuzumabom te 3 i 8 mjeseci nakon početka terapije trastuzumabom. Incidencija trastuzumabom inducirane kardiotoksičnosti nije pokazala statistički značajnu razliku između mlađih i starijih bolesnica, osim u grupi starijih bolesnica sa kardiovaskularnim rizikom, koje su imale značajno veću incidenciju srčanog popuštanja

Povezivanje mehanizama kemorezistentnosti tumorskih stanica i suboptimalnih sistemskih citotoksičnih rezultata liječenja

Systemic cytotoxic chemotherapeutic treatment of malignant tumors does not fully meet its goal due to the resistance of present tumor cells to the applied therapy. Chemoresistance is complex and multifactorial, caused by numerous mechanisms that alter drug concentration in the cell, by changes in expression of the epidermal growth factor and by activation of intracellular signaling pathways PI3K / Akt and MAPK. The factor of chemoresistance is also an increased level of antioxidative glutathione and glutathione transferase – S enzyme and the presence of tumor stem cells that signifi cantly improve protection of DNA from damage. Apart from cellular factors, resistance is influenced by extracellular hypoxia and acidosisand autophagy. Overcoming the chemoresistance is possible by using nanomechanisms for delivery of drugs to tumor cells, autophagy inhibitors like antimalarials chloroquine and hydroxychloroquine and plant polyphenols. By better understanding the mechanisms of chemoresistance and it’s overcoming it can be possible to achieve improvement in antitumor treatment.Sustavno citotoksično kemoterapijsko liječenje zloćudnih tumora ne ispunjava u potpunosti svoj cilj zbog prisutne kemorezistencije tumorskih stanica na primjenjenu terapiju. Kemorezistencija je kompleksna i uzrokovana brojnim mehanizmima koji mijenjaju koncentraciju lijeka u stanici, promjenama u ekspresiji epidermalnog čimenika rasta i aktivacije unutarstaničnih signalnih puteva PI3K/Akt i MAPK. Čimbenik kemorezistencije je porast antioksidativnog enzima glutationa i glutation-S transferaze te prisustvo matičnih stanica karcinoma koje značajno bolje štite DNA od oštećenja. Osim staničnih čimbenika, na rezistenciju utječe ekstracelularna hipoksija i acidoza te autofagija. Prevladavanje kemorezistencije moguće je primjenom nanomehanizama u dostavi lijekova u tumorske stanice, inhibitorima autofagije antimalaricima klorokinom i hidroksiklorokinom te biljnim polifenolima. Poznavanjem mehanizama kemorezistencije i njezinim nadilaženjem moguće je poboljšati dobrobit antitumorskog liječenja

Procjena nutritivnog rizika bolesnika tijekom sustavnog antineoplastičnog liječenja

This study aims to explore if there is a change in nutritional risk and body mass index (BMI) in cancer patients during the systemic antineoplastic treatment. We retrospectively analyzed data collected from 216 cancer patients treated at the Department of Medical Oncology, University Hospital for tumors, Sestre Milosrdnice University Hospital Center, Zagreb, Croatia, with systemic antineoplastic therapy in the period from 05/2016 to 05/2018. In our study, we included both patients treated with systemic therapy for the first time and patients treated repeatedly (only patients who have had at least six months free period after the last treatment course were eligible). We included male and female patients with breast cancer, colorectal cancer, pancreatic cancer, and head and neck cancer. Around 75% of patients had metastatic disease. We analyzed data collected from Nutritional Risk Score-2002 (NRS-2002) screening and results of BMI, at first hospitalization, and after three months of systemic antineoplastic treatment. All patients at high nutritional risk (NRS 3-4) received the nutritional intervention, which included enteral nutritional supplement and education of patient and patient’s family about nutrition in oncological patients. We used the Wilcoxon test for the NRS score and t-test for a depended variable for BMI data. The initial average BMI of all patients was 26,45 kg/m². Of all screened patients, around 78% of them were at mild nutritional risk (NRS 1-2), while around 22% of them were at high nutritional risk (NRS 3-4). We recorded a statistically significant decrease both in NRS of the entire screened population of patients after three months of systemic antineoplastic treatment and after specific nutritional intervention in high-risk patients (most patients were at mild nutritional risk, while less than 8% of them were at high nutritional risk). There was no significant change in BMI in the observed period (average BMI was 26, 59 kg/m²). It seems, systemic antineoplastic treatment, along with early nutritional intervention with enteral nutritive supplementation and education, can significantly contribute to the decrease of the nutritional risk.Cilj ovog rada je procijeniti promjena u nutritivnom riziku i indeksu tjelesne mase (ITM) onkoloških bolesnika tijekom sustavnog antineoplastičnog liječenja. Retrospektivno su analizirani podatci 216 bolesnika koji su od 05/2016 do 05/2018 liječeni na Odjelu internističke onkologije Klinike za tumore, KBC Sestre milosrdnice, Zagreb, Hrvatska. Obuhvaćeni su bolesnici po prvi put liječeni sustavnom antineoplastičnom terapijom i/ili koji u prethodnih 6 mjeseci nisu bili liječeni niti jednim vidom onkološkog liječenja. Zastupljeni su bolesnici obaju spolova, oboljeli od raka dojke, debelog i završnog crijeva, gušterače te glave i vrata. Oko 75% bolesnika imalo je metastatsku bolest. Korišteni su rezultati NRS 2002 nutritivnog probira te rezultati indirektne procjene sastava tijela izračunom indeksa tjelesne mase (ITM) prilikom prve hospitalizacije te nakon 3 mjeseca sustavnog antineoplastičnog liječenja. U svih bolesnika koji su bili u visokom nutritivnom riziku (NRS 3-4) je provedena nutritivna intervencija uvođenjem enteralne prehrane te edukacije bolesnika i obitelji o prehrani onkoloških bolesnika. Za statistički izračun su korišteni Wilcoxonov test za podatke o NRS-u te t-test za zavisne uzorke za podatke o ITM-u. Inicijalni prosječni ITM je na početku liječenja bio 26,45 kg/m². Inicijalnim nutritivnim probirom je utvrđen blagi nutritivni rizik (NRS 1-2) u oko 78% bolesnika, a oko 22% bolesnika je bilo u visokom nutritivnom riziku (NRS 3-4). Nakon 3 mjeseca specifičnog onkološkog liječenja te provođenja nutritivne potpore u visoko ugroženih bolesnika, zabilježen je statistički značajan pad u nutritivnom riziku u ukupnoj ispitivanoj populaciji (većina bolesnika je bila u blagom nutritivnom riziku, dok je manje od 8% bolesnika bilo visokog nutritivnog rizika). U periodu praćenja nije bila zabilježena značajnija promjena u indeksu tjelesne mase (prosječni ITM je bio 26,59 kg/m²). Sustavno antineoplastično liječenje uz ranu nutritivnu intervenciju i edukaciju doprinosi smanjenju znakova bolesti i poboljšanju općeg stanja bolesnika te može značajno smanjiti nutritivni rizik

Taksani u liječenju ranog raka dojke

Taxanes are irreplaceble drugs in treatment of many solid malignancies. In breast cancer they represent the backbone of adjuvant therapy and are important option in treatment of advanced and metastatic disease. Since their discovery in 1960’s they went through a long journey of clinical development and positioning in clinical practise of treatment of early breast cancer. Taxanes belong to the fourth group of cytotoxic drugs, which act as mytotic inhibitors, causing the death of the cell in metaphase. Clinical trials conducted in patients with breast cancer evaluated different combinations of other chemotherapeutics with taxanes, different modes of administration, effectiveness of different chemotherapy regimens including taxanes in different subtypes and stages of the disease and effectiveness of individual taxanes in comparison with one another. Based on the results of those trials, today the relevant global oncology associations reccomend the use of taxanes in treatment of early breast cancer, pointing out their significant benefit in total reduction of breast cancer mortality and risk of disease reccurence by 20-30% comparing to anthracycline only protocols. The purpose of this literature review was to provide comprehensive information about development of taxanes and their position in routine everyday clinical practise.Taksani su nezamjenjivi lijekovi u liječenju mnogih solidnih tumora. U karcinomu dojke predstavljaju okosnicu adjuvantne terapije i važna su opcija u liječenju uznapredovale i metastatske bolesti. Od njihovog otkrića 1960-ih prošli su dugi put kliničkog razvoja i pozicioniranja u kliničkoj praksi liječenja ranog raka dojke. Taksani pripadaju četvrtoj skupini citotoksičnih lijekova koji djeluju kao inhibitori mitoze, koji uzrokuju smrt stanice u metafazi. Klinička istraživanja provedena na bolesnicama s karcinomom dojke procjenjivala su različite kombinacije drugih kemoterapeutika s taksanima, različite načine primjene, djelotvornost različitih kemoterapijskih protokola koji uključuju taksane u različitim podtipovima i stadijima bolesti te učinkovitosti pojedinih taksana u usporedbi s drugim. Na temelju rezultata tih pokusa, danas relevantne globalne onkološke udruge preporučuju uporabu taksana u liječenju ranog raka dojke, pokazujući njihovu značajnu korist u ukupnom smanjenju rizika od smrti i povrata bolesti za 20-30% u odnosu na protokole bazirane samo na antraciklinu. Svrha ovog pregleda literature je pružanje sveobuhvatne informacije o razvoju taksana i njihove pozicije u rutinskoj svakodnevnoj kliničkoj praksi