PURPOSE: To determine the optimal daunorubicin dose and number of 7 + 3 induction cycles in newly diagnosed AML, this randomized controlled trial compared a once daily dose of 60 mg/m2 with 90 mg/m2 daunorubicin in the first 7 + 3 induction and one versus two cycles of 7 + 3 induction. PATIENTS AND METHODS: Patients age 18-65 years with newly diagnosed AML were randomly assigned to 60 versus 90 mg/m2 daunorubicin once daily plus cytarabine. Patients with marrow blasts below 5% on day 15 after first induction were randomly assigned to receive a second induction cycle or no second induction cycle. RESULTS: Eight hundred and sixty-four patients with a median age of 52 years were randomly assigned. After a preplanned interim analysis showing no significant difference in response between 60 and 90 mg/m2, all consecutive patients received 60 mg/m2 daunorubicin once daily. The proportion of good early responders was 44% versus 48% (P = .983) with a composite complete remission (CRc) rate of 90% versus 89% after induction (P = .691); the 3-year relapse-free survival (RFS) after 60 versus 90 mg/m2 once daily was 54% versus 50% (P = .561), and the 3-year overall survival (OS) was 65% versus 58% (P = .242). Among 389 good responders, CRc rates at the end of induction were 87% after single induction and 85% after double induction. The 3-year RFS was 51% versus 60% (hazard ratio [HR], 1.3; P = .091), and the 3-year OS was 76% versus 75% after single versus double induction (HR, 1.0; P = .937). CONCLUSION: The use of 90 mg/m2 daunorubicin once daily in the context of classical 7 + 3 induction does not significantly improve early response and does not lead to higher remission rates or longer survival than 60 mg/m2 once daily. In patients with a good early response after first induction, a second induction has only a limited impact on RFS and does not result in an OS benefit.
- MeSH
- akutní myeloidní leukemie * farmakoterapie mortalita MeSH
- cytarabin * aplikace a dávkování MeSH
- daunomycin * aplikace a dávkování MeSH
- dospělí MeSH
- indukce remise MeSH
- indukční chemoterapie * metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- protinádorová antibiotika aplikace a dávkování MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití aplikace a dávkování MeSH
- rozvrh dávkování léků MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
Malignant lymphoma survivors are at increased risk for anthracycline and/or radiotherapy-induced chronic cardiotoxicity. Proper long-term follow-up is essential for malignant lymphoma survivors after-care. This study aimed to assess TTE parameters of potential subclinical cardiotoxicity and to examine their utility in diagnosing chronic cardiotoxicity. Improvement of the diagnostic process may precede the manifestation of cardiac adverse events. Main objective of the study was to improve the identification of cancer survivors in increased risk of treatment cardiotoxicity. To achieve this goal, utility of various echocardiography parameters was examined.In this retrospective study we analysed TTE of 167 subjects with speckle tracking according to the European Society of Echocardiography guidelines during the follow-up period. 88 of them were long-term lymphoma survivors diagnosed with malignant lymphoma between the years 1994-2015. Minimum follow up period was 5 years with the median of 10 years after anti-cancer treatment cessation. TTE were performed between the years 2017-2022 at cardio-oncology outpatient office during regular follow-up period. A total of 79 volunteers with no history of chronic heart failure (CHF) or decline in LVEF, 51 (64.6%) of whom were males, with the median age of 46 (16-58) years were included in the analysis as control group. Control subjects had various indications for TTE (e.g. preoperative examination, benign palpitations, or with well controlled arterial hypertension taking two antihypertensives at most). Ischemic heart disease was ruled out by stress test. None of the control subjects had history of stroke or chronic lower limb ischemia. All control subjects were considered clinically stable with no sign of cardiac impairment caused by primary disease. Both cancer survivors and control group were divided into subgroups based on LVEF: lower normal LVEF (53-61%), and higher normal LVEF (> 61%). Survivors with lower normal LVEF (53-61%) had a statistically significant decline in GLS compared to those with higher normal LVEF (> 61%). This phenomenon was not observed in control group indicating a possible additional diagnostic value of this parameter. Inclusion of GLS assessment in follow-up TTE examination of subjects with lower normal LVEF may improve the sensitivity of detection of chronic cardiotoxicity. Patients with declined GLS and lower normal LVEF are candidates for intensified follow-up to precede manifestation of cardiac adverse events.
- MeSH
- antracykliny škodlivé účinky MeSH
- dospělí MeSH
- echokardiografie * MeSH
- funkce levé komory srdeční účinky léků MeSH
- globální longitudinální strain MeSH
- kardiotoxicita * etiologie diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfom * farmakoterapie MeSH
- mladiství MeSH
- mladý dospělý MeSH
- následné studie MeSH
- přežívající onkologičtí pacienti * MeSH
- retrospektivní studie MeSH
- tepový objem účinky léků MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Using an active targeting approach of chemotherapeutics-loaded nanocarriers (NCs) with monoclonal antibodies is a potential strategy to improve the specificity of the delivery systems and reduce adverse reactions of chemotherapeutic drugs. Specific targeting of the human epidermal growth factor receptor-2 (HER-2), expressed excessively in HER-2-positive breast cancer cells, can be achieved by conjugating NCs with an anti-HER-2 monoclonal antibody. We constructed trastuzumab-conjugated chitosan iodoacetamide-coated NCs containing doxorubicin (Tras-Dox-CHI-IA-NCs) as a tumor-targeted drug delivery system, during the study. Chitosan-iodoacetamide (CHI-IA) was synthesized and utilized to prepare trastuzumab-conjugated NCs (Tras-NCs). The morphology, physicochemical properties, drug loading, drug release, and biological activities of the NCs were elucidated. The Tras-NCs were spherical, with a particle size of approximately 76 nm, and had a positive zeta potential; after incorporating the drug, the size of the Tras-NC increased. A prolonged, 24-h drug release from the NCs was achieved. The Tras-NCs exhibited high cellular accumulation and significantly higher antitumor activity against HER-2-positive breast cancer cells than the unconjugated NCs and the drug solution. Therefore, Tras-Dox-CHI-IA-NCs could be a promising nanocarrier for HER-2-positive breast cancer.
- MeSH
- chitosan * chemie MeSH
- doxorubicin chemie MeSH
- jodacetamid MeSH
- lékové transportní systémy MeSH
- lidé MeSH
- monoklonální protilátky chemie MeSH
- nádory prsu * farmakoterapie MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- trastuzumab MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE: We report an analysis of minimal residual/detectable disease (MRD) as a predictor of outcome in previously untreated patients with follicular lymphoma (FL) from the randomized, multicenter GALLIUM (ClinicalTrials.gov identifier: NCT01332968) trial. PATIENTS AND METHODS: Patients received induction with obinutuzumab (G) or rituximab (R) plus bendamustine, or cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or cyclophosphamide, vincristine, prednisone (CVP) chemotherapy, followed by maintenance with the same antibody in responders. MRD status was assessed at predefined time points (mid-induction [MI], end of induction [EOI], and at 4-6 monthly intervals during maintenance and follow-up). Patients with evaluable biomarker data at diagnosis were included in the survival analysis. RESULTS: MRD positivity was associated with inferior progression-free survival (PFS) at MI (hazard ratio [HR], 3.03 [95% CI, 2.07 to 4.45]; P < .0001) and EOI (HR, 2.25 [95% CI, 1.53 to 3.32]; P < .0001). MRD response was higher after G- versus R-chemotherapy at MI (94.2% v 88.9%; P = .013) and at EOI (93.1% v 86.7%; P = .0077). Late responders (MI-positive/EOI-negative) had a significantly poorer PFS than early responders (MI-negative/EOI-negative; HR, 3.11 [95% CI, 1.75 to 5.52]; P = .00011). The smallest proportion of MRD positivity was observed in patients receiving bendamustine at MI (4.8% v 16.0% in those receiving CHOP; P < .0001). G appeared to compensate for less effective chemotherapy regimens, with similar MRD response rates observed across the G-chemo groups. During the maintenance period, more patients treated with R than with G were MRD-positive (R-CHOP, 20.7% v G-CHOP, 7.0%; R-CVP, 21.7% v G-CVP, 9.4%). Throughout maintenance, MRD positivity was associated with clinical relapse. CONCLUSION: MRD status can determine outcome after induction and during maintenance, and MRD negativity is a prerequisite for long-term disease control in FL. The higher MRD responses after G- versus R-based treatment confirm more effective tumor cell clearance.
- MeSH
- bendamustin hydrochlorid MeSH
- cyklofosfamid MeSH
- doxorubicin MeSH
- folikulární lymfom * MeSH
- galium * terapeutické užití MeSH
- lidé MeSH
- prednison MeSH
- protokoly protinádorové kombinované chemoterapie škodlivé účinky MeSH
- reziduální nádor farmakoterapie MeSH
- rituximab MeSH
- vinkristin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
STUDY QUESTION: What is the impact of the EuroNet-PHL-C2 treatment for boys with classical Hodgkin lymphoma (cHL) on semen parameters? SUMMARY ANSWER: More than half of the patients (52%, n = 16/31) had oligozoospermia or azoospermia at 2 years from cHL diagnosis; particularly boys treated for advanced-stage cHL had low sperm counts and motility. WHAT IS KNOWN ALREADY: Chemotherapy and radiotherapy to the inguinal region or testes can impair spermatogenesis and result in reduced fertility. The EuroNet-PHL-C2 trial aims to minimize radiotherapy in standard childhood cHL treatment, by intensifying chemotherapy. The present study aims to assess the (gonadotoxic) impact of this treatment protocol on semen parameters and reproductive hormones in boys aged ≤18 years. STUDY DESIGN, SIZE, DURATION: This international, prospective, multi-centre cohort study was an add-on study to the randomized phase-3 EuroNet-PHL-C2 trial, where the efficacy of standard cHL treatment with OEPA-COPDAC-28 (OEPA: vincristine, etoposide, prednisone, and doxorubicin; COPDAC-28: cyclophosphamide, vincristine, prednisone, and dacarbazine) was compared to intensified OEPA-DECOPDAC-21 chemotherapy (DECOPDAC-21: COPDAC with additional doxorubicin and etoposide and 25% more cyclophosphamide). Patients were recruited between January 2017 and September 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eligibility criteria included male patients, diagnosed with classical HL before or at the age of 18 years, and treated according to the EuroNet-PHL-C2 protocol in any of the 18 participating sites in the Netherlands, Germany, Belgium, Czech Republic, and Austria. Sperm parameters (sperm concentration, progressive motility, sperm volume, and calculated total motile sperm count) were assessed at diagnosis and 2 years after diagnosis in (post)pubertal boys. Laboratory measurements (serum follicle-stimulating hormone (FSH) and inhibin B) were performed in samples drawn at diagnosis, during treatment (2-3 times), and at 2 years post-diagnosis, and (age-adjusted) analyses were conducted separately for pre-pubertal and (post)pubertal boys. Outcomes were compared between the treatment levels (TL1, TL2, and TL3) and consolidation treatment schemes (COPDAC-28 and DECOPDAC-21). MAIN RESULTS AND THE ROLE OF CHANCE: In total, 101 boys were included in the present analysis: 73 were (post)pubertal (median age 15.4 years, (IQR 14.4; 16.6), 10 TL1, 29 TL2, 34 TL3, 62% of TL2/3 patients received COPDAC-28) and 28 boys were pre-pubertal (median age 9.6 years (IQR 6.6; 11.4), 4 TL1, 7 TL2, 17 TL3, 38% of TL2/3 patients received COPDAC-28). The study included six boys who had received pelvic radiotherapy; none were irradiated in the inguinal or testicular area. At diagnosis, 48 (post)pubertal boys delivered semen for cryopreservation; 19 (40%) semen samples were oligospermic and 4 (8%) were azoospermic. Low sperm concentration (<15 mil/ml) appeared to be related to the HL disease itself, with a higher prevalence in boys who presented with B symptoms (76% vs 26%, aOR 2.3 (95% CI 1.0; 3.8), P = 0.001) compared to those without such symptoms. At 2 -years post-diagnosis, 31 boys provided semen samples for analysis, of whom 12 (39%) boys had oligozoospermia and 4 (13%) had azoospermia, while 22 boys (71%) had low total motile sperm counts (TMSC) (<20 mil). Specifically, the eight boys in the TL3 group treated with DECOPDAC-21 consolidation had low sperm counts and low progressive motility after 2 years (i.e. median sperm count 1.4 mil/ml (IQR <0.1; 5.3), n = 7 (88%), low sperm concentration, low median progressive motility 16.5% (IQR 0.0; 51.2), respectively). Age-adjusted serum FSH levels were significantly raised and inhibin B levels (and inhibin B:FSH ratios) were decreased during chemotherapy in (post)pubertal boys, with subsequent normalization in 80% (for FSH) and 60% (for inhibin B) of boys after 2 years. Only 4 out of the 14 (post)pubertal boys (29%) with low sperm concentrations after 2 years had elevated FSH (>7.6 IU/l), while 7 (50%) had low inhibin B levels (<100 ng/l). In pre-pubertal boys, reproductive hormones were low overall and remained relatively stable during chemotherapy. LIMITATIONS, REASONS FOR CAUTION: The present analyses included sperm and laboratory measurements up to 2 years post-diagnosis. Long-term reproductive outcomes and potential recovery of spermatogenesis remain unknown, while recovery was reported up to 5- or even 10-year post-chemotherapy in previous studies.Boys who were pre-pubertal at diagnosis were still too young and/or physically not able to deliver semen after 2 years and we could not assess a potential difference in gonadotoxicity according to pubertal state at the time of treatment. Overall, the statistical power of the analyses on sperm concentration and quality after 2 years was limited. WIDER IMPLICATIONS OF THE FINDINGS: Results of the semen analyses conducted among the 31 boys who had provided a semen sample at 2 years post-treatment were generally poor. However, additional long-term and adequately powered data are crucial to assess the potential recovery and clinical impact on fertility. The participating boys will be invited to deliver a semen sample after 5 years. Until these data become available, benefits of intensified chemotherapy in cHL treatment to reduce radiotherapy and lower risk for development of secondary tumours should be carefully weighed against potentially increased risk of other late effects, such as diminished fertility due to the increased chemotherapy burden. Boys with newly diagnosed cHL should be encouraged to deliver sperm for cryopreservation whenever possible. However, patients and clinicians should also realize that the overall state of disease and inflammatory milieu of cHL can negatively affect sperm quality and thereby reduce chance of successful fertility preservation. Furthermore, the measurement of FSH and inhibin B appears to be of low value in predicting low sperm quality at two years from cHL treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the Dutch charity foundation KiKa (project 257) that funds research on all forms of childhood cancer. C.M.-K., D.K., W.H.W., D.H., MC, A.U., and A.B. were involved in the development of the EuroNet-PHL-C2 regimen. The other authors declare no potential conflict of interest. TRIAL REGISTRATION NUMBER: N/A.
- MeSH
- analýza spermatu MeSH
- azoospermie farmakoterapie MeSH
- cyklofosfamid * terapeutické užití MeSH
- dakarbazin terapeutické užití MeSH
- dítě MeSH
- doxorubicin terapeutické užití škodlivé účinky MeSH
- etoposid terapeutické užití aplikace a dávkování MeSH
- folikuly stimulující hormon krev MeSH
- Hodgkinova nemoc * farmakoterapie MeSH
- inhibiny krev MeSH
- lidé MeSH
- mladiství MeSH
- motilita spermií účinky léků MeSH
- oligospermie farmakoterapie MeSH
- počet spermií MeSH
- prednison terapeutické užití aplikace a dávkování MeSH
- předškolní dítě MeSH
- prospektivní studie MeSH
- protokoly protinádorové kombinované chemoterapie * terapeutické užití škodlivé účinky MeSH
- vinkristin terapeutické užití MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- MeSH
- doxorubicin farmakologie terapeutické užití MeSH
- inhibitory kontrolních bodů klasifikace terapeutické užití MeSH
- ipilimumab farmakologie terapeutické užití MeSH
- leiomyosarkom farmakoterapie MeSH
- melanom diagnóza farmakoterapie MeSH
- nádory žaludku farmakoterapie MeSH
- nivolumab farmakologie terapeutické užití MeSH
- protokoly protinádorové léčby MeSH
- trabektedin farmakologie terapeutické užití MeSH
- Publikační typ
- souhrny MeSH
Východiská: Vývoj vysoko účinných protinádorových terapií za posledných niekoľko desaťročí zásadným spôsobom zmenil situáciu pacientov so zhubným nádorovým ochorením, ktorí v súčasnosti dosahujú vysokú mieru vyliečenia v skorých štádiách ochorenia. Napriek obrovskému pokroku chemoterapia naďalej zostáva základnou liečebnou modalitou včasného karcinómu prsníka. Komplikácie súvisiace s chemoterapiou majú však zásadný vplyv na kardiovaskulárnu morbiditu a mortalitu tejto skupiny pacientov. Takmer 80 % žien s diagnostikovanou rakovinou prsníka má viac ako 50 rokov a má prítomné rizikové faktory pre kardiovaskulárne ochorenie, ako je vek, rodinná anamnéza, hypertenzia, zvýšený cholesterol, fajčenie, cukrovka a zvýšený index telesnej hmotnosti. Väčšina pacientok na rakovinu prsníka nezomrie a v súlade s celkovou populáciou zostávajú kardiovaskulárne ochorenia najčastejšou príčinou úmrtia. Preklinický výskum, retrospektívne analýzy a zopár prospektívných prác popisujú dyslipidemický účinok cytostatík, ktorý môže predisponovať k vzniku aterosklerotických kardiovaskulárnych ochorení. Podanie neoadjuvantnej alebo adjuvantnej chemoterapie na báze antracyklínov a taxánov môže viesť k zvýšeniu celkového cholesterolu, triacylglyceridov, LDL cholesterolu a poklesu HDL cholesterolu. Abnormálne vysoké koncentrácie lipidov v krvi predstavujú jeden z hlavných rizikových faktorov pre rozvoj a progresiu kardiovaskulárnych ochorení. Práce naznačujú i koreláciu medzi hladinami sérových lipidov a mierou dosiahnutia patologickej kompletnej remisie po podaní neoadjuvantnej chemoterapie. Dyslipidémia je u pacientiek s rakovinou prsníka liečených neoadjuvantnou chemoterapiou asociovaná s horšou prognózou. Cieľ: Cieľom práce je poukázať na dyslipidemické účinky cytostatík a riziká vzniku aterosklerotických kardiovaskulárnych ochorení u pacientok s karcinómom prsníka, ktoré absolvovali adjuvantnú alebo neoadjuvantnú chemoterapiu pre včasný karcinóm prsníka. Identifikácia kardiovaskulárnych rizikových faktorov na začiatku onkologickej liečby, monitorácia lipidového spektra a včasná intervencia liečby dyslipidémie unikajú v súčasnosti pozornosti.
Backround: The development of highly effective anti-cancer therapies over the past several decades has dramatically changed the situation of patients with malignant tumor disease, who currently achieve a high rate of cure in the early stages of the disease. Despite tremendous progress, chemotherapy remains the primary treatment modality for early breast cancer. However, chemotherapy-related complications have a major impact on cardiovascular morbidity and mortality in this group of patients. Almost 80% of women diagnosed with breast cancer are over 50 years of age and already have risk factors for cardiovascular disease, such as age, family history, hypertension, elevated cholesterol, smoking, diabetes, and elevated body mass index. Most breast cancer patients do not die and, in line with the general population, cardiovascular disease remains the most common cause of death. Clinical research, extensive retrospective analyzes and prospective works describe the dyslipidemic effect of cytostatics, which may predispose to the development of atherosclerotic cardiovascular diseases. The administration of neoadjuvant or adjuvant chemotherapy based on anthracyclines and taxanes can lead to an increase in total cholesterol, triacylglycerides, LDL cholesterol and a decrease in HDL cholesterol. Abnormally high concentrations of lipids in the blood represent one of the main risk factors for the development and progression of cardiovascular diseases. The works also indicate a correlation between serum lipid levels and the rate of achieving pathological complete remission after the administration of neoadjuvant chemotherapy. Dyslipidemia is associated with a worse prognosis in breast cancer patients treated with neoadjuvant chemotherapy. Purpose: The aim of the thesis is to point out the dyslipidemic effects of cytostatics and the risks of atherosclerotic cardiovascular diseases in breast cancer patients who have undergone adjuvant or neoadjuvant chemotherapy for early breast cancer. The identification of cardiovascular risk factors at the beginning of oncological treatment, the monitoring of the lipid spectrum during the treatment and the timely intervention of dyslipidemia treatment escape attention at present.
- MeSH
- antracykliny farmakologie terapeutické užití MeSH
- cytostatické látky * farmakologie škodlivé účinky terapeutické užití MeSH
- dyslipidemie * chemicky indukované etiologie krev MeSH
- farmakoterapie klasifikace metody MeSH
- kardiovaskulární nemoci chemicky indukované etiologie MeSH
- lidé MeSH
- nádory prsu diagnóza epidemiologie farmakoterapie MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
All anthracyclines, including doxorubicin (DOXO), the most common and still indispensable drug, exhibit cardiotoxicity with inherent risk of irreversible cardiomyopathy leading to heart failure with reduced ejection fraction (HFrEF). Current pharmacological strategies are clearly less effective for this type of HFrEF, hence an urgent need for new therapeutic approaches. The prerequisite for success is thorough understanding of pathophysiology of this HFrEF form, which requires an appropriate animal model of the disease. The aim of this study was to comprehensively characterise a novel model of HF with cardiorenal syndrome, i.e. DOXO-induced HFrEF with nephrotic syndrome, in which DOXO was administered to Ren-2 transgenic rats (TGR) via five intravenous injections in a cumulative dose of 10 mg/kg of body weight (BW). Our analysis included survival, echocardiography, as well as histological examination of the heart and kidneys, blood pressure, but also a broad spectrum of biomarkers to evaluate cardiac remodelling, fibrosis, apoptosis, oxidative stress and more. We have shown that the new model adequately mimics the cardiac remodelling described as "eccentric chamber atrophy" and myocardial damage typical for DOXO-related cardiotoxicity, without major damage of the peritoneum, lungs and liver. This pattern corresponds well to a clinical situation of cancer patients receiving anthracyclines, where HF develops with some delay after the anticancer therapy. Therefore, this study may serve as a comprehensive reference for all types of research on DOXO-related cardiotoxicity, proving especially useful in the search for new therapeutic strategies.
- MeSH
- doxorubicin * škodlivé účinky MeSH
- krysa rodu rattus MeSH
- ledviny účinky léků patofyziologie MeSH
- modely nemocí na zvířatech * MeSH
- nefrotický syndrom * chemicky indukované farmakoterapie patofyziologie MeSH
- oxidační stres účinky léků MeSH
- potkani transgenní * MeSH
- protinádorová antibiotika škodlivé účinky MeSH
- srdeční selhání * chemicky indukované patofyziologie MeSH
- tepový objem * účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- ABC transportéry MeSH
- cytostatické látky aplikace a dávkování terapeutické užití MeSH
- doxorubicin aplikace a dávkování terapeutické užití MeSH
- geny MDR MeSH
- inhibitory HIV-proteasy farmakologie terapeutické užití MeSH
- inhibitory proteas farmakologie terapeutické užití MeSH
- lidé MeSH
- Lopinavir aplikace a dávkování terapeutické užití MeSH
- mnohočetná léková rezistence * účinky léků MeSH
- nádory farmakoterapie MeSH
- nanočásticový lékový transportní systém MeSH
- P-glykoprotein metabolismus účinky léků MeSH
- protinádorové látky aplikace a dávkování terapeutické užití MeSH
- transkripční faktor STAT3 metabolismus MeSH
- Check Tag
- lidé MeSH
Neoadjuvant chemotherapy (NAC) is the preferred treatment option in locally advanced breast cancer (BC). The administration of NAC is associated with a wide range of adverse effects. This pilot observational prospective study examined the effect of NAC using anthracycline + cyclophosphamide (AC) followed by paclitaxel (PTx) on a portfolio of 22 plasma and urinary amino acids, plasma proteins (albumin, prealbumin, transferrin), and products of nitrogen metabolism (urea, creatinine, uric acid) in plasma and urine. Plasma and 24-h urine samples were obtained from ten patients with early breast cancer (N1-3 N0-2 M0), at the following time points: before the start of NAC and during the AC/PTx treatment period (a total of 8 measurements at three-weekly intervals). Amino acids were analyzed using ion exchange chromatography. There were no significant differences in the measured parameters in plasma and urine between pre-NAC and during AC- and PTx-treatment. No trend was detected. A significant difference in the portfolio of plasma and urinary amino acids was found only in the pre-treatment period compared to the control group. Levels of eight plasma amino acids (8/22) were significantly reduced and those of nine urine amino acids were increased (9/22). Nitrogenous catabolites in plasma and urine were not indicative of increased protein catabolism during the anthracycline and taxane treatment periods. A slightly positive nitrogen balance was accompanied by an average weight gain of 3.3 kg (range 0-6 kg). The AC/PTx treatment regimen did not cause significant changes in the monitored laboratory parameters.
- MeSH
- aminokyseliny * moč krev MeSH
- antracykliny terapeutické užití aplikace a dávkování MeSH
- cyklofosfamid * terapeutické užití MeSH
- dospělí MeSH
- dusík * moč MeSH
- kreatinin moč krev MeSH
- krevní proteiny * metabolismus analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory prsu * farmakoterapie krev moč MeSH
- neoadjuvantní terapie * MeSH
- paclitaxel * terapeutické užití aplikace a dávkování MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- protokoly protinádorové kombinované chemoterapie terapeutické užití MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH