OBJECTIVES: Patients with head and neck squamous cell carcinoma (HNSCC) can experience severe symptom burden and/or difficulty swallowing, leading to problems with treatment adherence/administration. In LUX-Head and Neck 1 (LH&N1; NCT01345682), second-line afatinib improved progression-free survival (PFS) versus methotrexate in patients with recurrent/metastatic HNSCC. We report adherence and safety across pre-specified and additional subgroups potentially linked to afatinib PFS benefit in LH&N1 (p16 status, smoking history), and afatinib adherence, safety and efficacy by administration (oral versus feeding tube; post-hoc analysis). METHODS: Patients were randomized (2:1) to afatinib (40 mg/day) or intravenous methotrexate (40 mg/m2/week). RESULTS: Among 320 afatinib-treated and 160 methotrexate-treated patients, 83-92% and 76-92% (of patients with data available) across all subgroups took ≥80% of treatment. Across p16 status and smoking history subgroups, the most common treatment-related adverse events (AEs) were diarrhea (70-91%), rash/acne (72-84%), stomatitis (34-73%) with afatinib; and included stomatitis (39-100%), fatigue (22-50%), nausea (19-36%) with methotrexate. Dose reduction decreased AE incidence/severity. Baseline characteristics were generally similar between oral/feeding tube (n = 276/n = 46) groups. 89%/89% (of patients with data available) took ≥80% of assigned afatinib. Median PFS was 2.6 versus 2.7 months (hazard ratio: 0.997; 95% confidence interval: 0.72-1.38). The most common afatinib-related AEs were: rash/acne (74% versus 74%), diarrhea (73% versus 65%), stomatitis (40% versus 30%). CONCLUSION: Subgroup analyses of LH&N1 demonstrate that afatinib has predictable and manageable safety across patient subgroups, with high treatment adherence, and is effective via oral and feeding tube administration.

• MeSH
• adherence a compliance při léčbě MeSH
• afatinib terapeutické užití   MeSH
• chinazoliny aplikace a dávkování   MeSH
• dlaždicobuněčné karcinomy hlavy a krku farmakoterapie   metabolismus   MeSH
• erbB receptory metabolismus   MeSH
• lidé MeSH
• lokální recidiva nádoru farmakoterapie   metabolismus   MeSH
• methotrexát aplikace a dávkování   MeSH
• nádory hlavy a krku farmakoterapie   metabolismus   MeSH
• přežití po terapii bez příznaků nemoci MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Urinary neopterin is increased in less than 20% of patients with breast carcinoma. Moderately increased neopterin concentrations are also known to accompany comorbid conditions commonly observed in patients with breast carcinoma, for example, diabetes mellitus or complications of atherosclerosis. In the present study, we evaluated the effect of the presence of comorbid conditions on urinary neopterin. A trend for higher neopterin concentrations was observed in patients with most of the comorbid conditions, but significantly higher neopterin was observed only in patients aged 70 years or older and in a heterogeneous group of patients with comorbidity other than diabetes mellitus, thyroid disorder, hyperlipidaemia, cardiac disorder or other malignancy. Significantly higher neopterin levels were noted in patients with two or more comorbid conditions. In conclusion, present data demonstrate an association between systemic immune activation reflected in increased urinary neopterin concentrations and age or presence of comorbid diseases in patients with breast carcinoma. A cumulative effect was observed with the presence of two or more comorbid conditions resulting in significantly increased urinary neopterin. These observations should be taken into account when interpreting the changes of parameters of systemic immune and inflammatory response in patients with breast carcinoma.

• MeSH
• ateroskleróza epidemiologie   MeSH
• chromatografie s reverzní fází MeSH
• komorbidita MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádorové biomarkery moč   MeSH
• nádory prsu moč   MeSH
• neopterin moč   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

A simple and rapid HPLC method requiring small volumes (250 microL) of human serum after C18 SPE sample preparation was developed using monolithic technology for simultaneous determination of all-trans-retinoic acid, 13-cis-retinoic acid, retinol, gamma- and alpha-tocopherol. The monolithic column, Chromolith Performance RP-18e (100x4.6 mm), was operated at ambient temperature. The mobile phase consisted of a mixture of acetonitrile (ACN) and 1% ammonium acetate in water (AMC) at pH 7.0. The mobile phase started at 98:2 (v/v) ACN/AMC (column pre-treatment) at a flow rate of 2 mL/min, then changed to 95:5 (v/v) ACN/AMC for 4 min at a flow rate of 1.5 mL/min and a further 3 min at a flow rate of 3.2 mL/min. Detection and identification were performed using a photodiode array detector. Retinol, 13-cis- and all-trans-retinoic acid were monitored at 325 nm. Both alpha- and gamma-tocopherol were detected at 295 nm. The total analysis time was 7.2 min. Tocol (synthesized tocopherol, not occurring in humans) was used as internal standard. The method was linear in the range of 0.125-10.00 micromol/L for all-trans-retinoic acid, 0.125-5.00 micromol/L for 13-cis-retinoic acid, 0.25-10.00 micromol/L for retinol, 0.5-50.00 micromol/L for gamma-tocopherol, and 0.5-50.00 micromol/L for alpha-tocopherol. The present method may be useful for monitoring of retinoids and tocopherols in clinical studies.

• MeSH
• lidé MeSH
• molekulární struktura MeSH
• nádory krev   terapie   MeSH
• reprodukovatelnost výsledků MeSH
• retinoidy chemie   krev   MeSH
• senzitivita a specificita MeSH
• tokoferoly chemie   krev   MeSH
• vysokoúčinná kapalinová chromatografie metody   přístrojové vybavení   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Aromatase inhibitors may affect lipid metabolism, inflammatory response and antioxidant balance. PATIENTS AND METHODS: One hundred and eighty-six post-menopausal patients with breast carcinoma underwent evaluation of parameters of lipid metabolism, inflammatory response and antioxidant balance immediately before as well as 2 and 4 months after the start of therapy with aromatase inhibitors. RESULTS: A significant increase in total, very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, lipoprotein (a), retinol, C-reactive protein and fibrinogen was observed. The changes of serum lipid concentrations were restricted mostly to the patients pre-treated with tamoxifen who had significantly lower baseline levels of these parameters. CONCLUSION: An increase of serum cholesterol, lipoprotein (a), C-reactive protein and fibrinogen in patients treated with aromatase inhibitors is the result of tamoxifen withdrawal rather than a direct effect of therapy. No significant changes in serum lipids were observed in patients treated with aromatase inhibitors in the first-line setting.

• MeSH
• alfa-tokoferol krev   MeSH
• antitumorózní látky hormonální farmakologie   MeSH
• C-reaktivní protein metabolismus   MeSH
• fibrinogen metabolismus   MeSH
• inhibitory aromatasy farmakologie   MeSH
• lidé MeSH
• lipoprotein (a) metabolismus   MeSH
• lipoproteiny LDL metabolismus   MeSH
• lipoproteiny VLDL metabolismus   MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• neopterin moč   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• tamoxifen farmakologie   MeSH
• vitamin A krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Among other actions, chemotherapy may induce an activation of systemic inflammatory and immune response. PATIENTS AND METHODS: Urinary neopterin was evaluated, using high-performance liquid chromatography, before and during dose-dense combination chemotherapy with doxorubicin, cyclophosphamide and sequential paclitaxel (neoadjuvant or adjuvant) in 194 patients with breast carcinoma. Hemoglobin, peripheral blood cell count and, in a subgroup of patients, iron metabolism were also evaluated. RESULTS: Urinary neopterin increased significantly during the chemotherapy. The increase in urinary neopterin was accompanied by a gradual decrease of hemoglobin. A marked increase in serum ferritin concentration was observed during the chemotherapy, along with fluctuations of iron concentrations. Among 161 patients treated with primary chemotherapy, the pathological response was evaluable in 150. Pathological complete response was observed in 37 cases (25%). In patients with pathological complete response, significantly lower serum ferritin concentrations were observed. CONCLUSION: Present data demonstrate the presence of systemic immune activation, reflected in increased urinary neopterin concentrations, in breast carcinoma patients treated with dose-dense chemotherapy. Lower ferritin concentrations were predictive of pathological complete response.

• MeSH
• adjuvantní chemoterapie MeSH
• cyklofosfamid aplikace a dávkování   MeSH
• dospělí MeSH
• doxorubicin aplikace a dávkování   MeSH
• ferritin krev   MeSH
• financování organizované MeSH
• hemoglobiny metabolismus   MeSH
• krevní obraz MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu u mužů farmakoterapie   krev   moč   MeSH
• nádory prsu MeSH
• neoadjuvantní terapie MeSH
• neopterin moč   MeSH
• paclitaxel aplikace a dávkování   MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• senioři MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH