Rijetke nuspojave terapije sunitinibom u bolesnice s metastatskim karcinomom bubrega: prikaz slučaja

Sunitinib is an orally administered multikinase inhibitor. This therapy can provoke uncommon side effects such as pancytopenia, tumor lysis syndrome, cardiac disorders, thromboembolic incidents, intestinal perforation, pancreatitis, acute renal failure, etc. We report a case of a 63-year-old female admitted to the hospital due to abdominal pain, nausea, vomiting and elevated blood pressure. One month earlier, sunitinib therapy for metastatic renal cell carcinoma was initiated. During the first cycle of therapy, after three weeks of sunitinib 50 mg daily, symptoms started and she stopped taking the drug. At admission, laboratory tests revealed elevated serum and urine amylase, C-reactive protein, urea and creatinine, and lowered platelet and leukocyte counts and hemoglobin value. Urine test showed proteinuria, erythrocyturia, leukocyturia and granulated cylinder. The patient was diagnosed with acute pancreatitis grade III, acute renal failure grade II, pancytopenia and urinary infection, and was hospitalized for five days. She was treated symptomatically and with antibiotic therapy because of persistently elevated C-reactive protein and pathologic urinary sediment, which led to subjective and clinical improvement. Acute pancreatitis, renal insufficiency and pancytopenia are rarely described side effects of sunitinib therapy, and clear connection between these conditions and drug activity is not yet determined. Medical specialists who prescribe and treat patients with sunitinib should be aware of the possible occurrence of these conditions and perform regular checkups of sunitinib treated patients.Sunitinib je oralni multikinazni inhibitor. Liječenje može izazvati pojavu rijetkih nuspojava kao što su pancitopenija, sindrom lize tumora, srčani poremećaji, tromboembolijski incidenti, perforacija crijeva, pankreatitis, akutno zatajenje bubrega itd. Ovdje prikazujemo slučaj 63-godišnje bolesnice hospitalizirane zbog bolova u trbuhu, mučnine, povraćanja i povišenog krvnog tlaka. Mjesec dana ranije je započela liječenje sunitinibom zbog metastatskog karcinoma bubrega. U bolesnice su se tijekom prvog ciklusa liječenja, nakon tri tjedna uzimanja 50 mg sunitiniba na dan, pojavili navedeni simptomi zbog čega je bolesnica prekinula uzimati lijek. Pri prijmu u bolnicu su laboratorijski nalazi pokazali povišene vrijednosti serumskih i mokraćnih amilaza, C-reaktivnog proteina, ureje i kreatinina, sniženi broj trombocita i leukocita te sniženu vrijednost hemoglobina. Postavljena je dijagnoza akutnog pankreatitisa gr. III., akutnog bubrežnog zatajenja gr. II, pancitopenije i urinarne infekcije te je bolesnica hospitalizirana tijekom pet dana. Liječena je simptomatski te antibiotikom zbog povišene vrijednosti C-reaktivnog proteina i patološkog sedimenta mokraće, što je dovelo do subjektivnog i kliničkog poboljšanja stanja. Akutni pankreatitis, bubrežno zatajenje i pancitopenija su rijetko opisivane nuspojave primjene sunitiniba i jasna veza između tih stanja i aktivnosti lijeka još nije utvrđena. Specijalisti koji propisuju i liječe bolesnike sunitinibom trebali bi biti svjesni mogućnosti pojave ovih stanja i provoditi redovite kontrole u bolesnika liječenih ovim lijekom

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

ASSOCIATION OF BREAST CANCER SYMPTOMS WITH PATIENTS’ QUALITY OF LIFE AND DEPRESSION; A CROATIAN CROSS-SECTIONAL STUDY

Aim: To find out which symptoms are the most associated with a breast cancer patients’ quality of life (QoL) and depression. Subjects and methods: We performed this cross-sectional study from February to April 2015 at the Department of Medical Oncology, University Hospital for Tumors, Zagreb University Hospital Center "Sestre milosrdnice", Zagreb, Croatia on the sample of 147 breast cancer patients. Primary outcomes were EORTC QLQ-C30 version 3.0 Global QoL scale and Beck Depression Inventory II. Results: After the adjustment for other symptoms, sociodemographic and clinical variables, fatigue (ȕ=-0.47, P<0.001), pain (ȕ=-0.24, P=0.023), and appetite loss (ȕ=-0.18, P=0.037) were statistically significantly correlated with QoL. Fatigue was the only symptom significantly associated with depression (ȕ=0.39, P=0.006). Conclusion: Fatigue, pain, appetite loss contributes the most to the overall breast cancer patients QoL. Although correlated, fatigue and pain contribution to lower QoL is independent from each other. Future studies should investigate whether there is an interaction between fatigue and pain changes over course of treatment. Fatigue and number of children are positively, while age and treatment in daily hospital are negatively associated with depression measured by BDI-II

USE OF IMMUNOTHERAPY IN THE TREATMENT OF A PATIENT WITH TWO SIMULTANEOUS METASTATIC DISEASES

Immunotherapy is an evolving and promising cancer treatment proven to significantly prolong survival in a multitude of oncological diseases. Nivolumab, a monoclonal antibody to the PD-1 receptor, is an immunotherapy used in the treatment of several cancers, including melanoma and renal cell carcinoma (RCC)

GISTs’ Classifications in Predicting Aggressive Behavior: A Single Institution Experience

Gastrointestinal stromal tumors (GISTs)are the most common mesenchymal neoplasms of the gastrointestinal tract. When making treatment plan it is very important to make proper tumor aggressiveness estimation. Traditionally, the best prognostic factors are tumor size and number of mitoses. The aim of this study was to define which GIST classifica- tion (Amin’s or Newman’s classification or Fletcher’s Consensus Criteria) is the most significant determining prognosis and has the strongest impact on survival. This study included 63 GIST patients whose tumor specimens were evaluated by standard histopathological methods and classified based on histological assessment of malignant behavior to the three different systems. Comparison of those classification systems was done and none of them was proven to be statisti- cally significantly better in predicting overall survival and probability of lethal outcome. We conclude that all three clas- sifications are comparable in prediction of malignant behavior. The worst prognostic factor is existence of metastases at the time of disease diagnosis

Sustavno liječenje karcinoma glave i vrata

Systemic therapy of head and neck carcinoma is reserved for locally advanced and metastatic disease. Concomitant use of cisplatin and irradiation is still standard protocol for treatment of locally advanced disease although immunoradiotherapy with cetuximab seems to be a good alternative with similar results. The best option for fi rst-line treatment of advanced or metastatic disease is polychemotherapy with addition of cetuximab in patients in good clinical condition. Limited options are available for second-line therapy mostly due to poor performance status of the patients. HPV-positive tumors make a special subgroup of HNSCC in which targeted therapy plays the most important role.Sustavno liječenje karcinoma glave i vrata je rezervirano za lokalno uznapredovalu i metastatsku bolest. Konkomitantna primjena cisplatine uz zračenje još uvijek predstavlja standard liječenja za lokalno uznapredovalu bolest, iako imunoradioterapija s cetuximabom predstavlja dobru alternativu sa sličnim rezultatima. Najbolja opcija za liječenje uznapredovale ili metastatske bolesti je polikemoterapija uz dodatak cetuximaba za sve bolesnike u dobrom kliničkom stanju. Mogućnosti druge linije liječenja su vrlo ograničene, najviše zbog lošeg općeg stanja bolesnika. HPV-pozitivni tumori predstavljaju posebnu podgrupu karcinoma pločastih stanica glave i vrata u kojima najvažniju ulogu igra liječenje ciljanom terapijom

Onkološko savjetovanje bolesnika i obitelji oboljelih od nasljednog karcinoma debelog crijeva

Colorectal cancer (CRC) is the third most common malignancy in the world. Thirty percent of all CRC cases are hereditary or familial forms of the disease. Approximately 5% of them represent well defined hereditary syndromes. Colon cancer syndromes are inherited autosomal dominant diseases, with exception of MUTYH associated polyposis, which is inherited in autosomal recessive manner. Most of CRC syndromes also carry significant risk of developing cancers of extra colonic localization.The clinician who deals with hereditary CRC patients should have a wide knowledge ofpresentation, genetics and cancer risks in hereditary CRC syndromes.In Croatia we donot have the center that systematically deals with CRC genetics, pharmacogenetics and hereditary CRC syndromes. Therefore, with this article, we systematically review the characteristics CRC syndromes.Kolorektalni karcinom je treći najčešći maligni tumor u svijetu. 30% slučajeva su nasljedni i familijarni oblici bolesti. Približno 5% nasljednih oblika čine dobro definirani nasljedni sindromi kolorektalnog karcinoma.To su nasljedne autosomno dominantne bolesti, s izuzetkom tzv. MUTYH polipoze koja se naslje|uje autosomno recesivno. Većina nasljednih sindroma kolorektalnog raka nosi rizik razvoja karcinoma drugih lokalizacija. Kliničar koji sudjeluje u liječenju oboljelih od kolorektalnog karcinoma trebao bi imati široko znanje o kliničkoj slici, genetici i rizicima za pojedine tumore u nasljednim sindromima kolorektalnog raka.U Hrvatskoj još uvijek nemamo centar koji bi se sustavno bavio genetikom kolorektalnog karcinoma, farmakogenetikom i nasljednim sindromima kolorektalnog raka. U ovom članku donosimo pregled i karakteristike nasljednih sindroma kolorektalnog raka

A patient with metastasis of breast cancer which was originally described as primary colorectal cancer: case report

Breast cancer metastases can be found in almost all organs in the body - but are most commonly found in the lungs, liver, bones, skin and brain. Metastatic breast cancer often occurs years or decades after initial diagnosis and treatment. In this case report, we will present a 62-year-old patient with metastasis of breast cancer which was originally described as primary colorectal cancer

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

Sustavno liječenje karcinoma glave i vrata

Systemic therapy of head and neck carcinoma is reserved for locally advanced and metastatic disease. Concomitant use of cisplatin and irradiation is still standard protocol for treatment of locally advanced disease although immunoradiotherapy with cetuximab seems to be a good alternative with similar results. The best option for fi rst-line treatment of advanced or metastatic disease is polychemotherapy with addition of cetuximab in patients in good clinical condition. Limited options are available for second-line therapy mostly due to poor performance status of the patients. HPV-positive tumors make a special subgroup of HNSCC in which targeted therapy plays the most important role.Sustavno liječenje karcinoma glave i vrata je rezervirano za lokalno uznapredovalu i metastatsku bolest. Konkomitantna primjena cisplatine uz zračenje još uvijek predstavlja standard liječenja za lokalno uznapredovalu bolest, iako imunoradioterapija s cetuximabom predstavlja dobru alternativu sa sličnim rezultatima. Najbolja opcija za liječenje uznapredovale ili metastatske bolesti je polikemoterapija uz dodatak cetuximaba za sve bolesnike u dobrom kliničkom stanju. Mogućnosti druge linije liječenja su vrlo ograničene, najviše zbog lošeg općeg stanja bolesnika. HPV-pozitivni tumori predstavljaju posebnu podgrupu karcinoma pločastih stanica glave i vrata u kojima najvažniju ulogu igra liječenje ciljanom terapijom