RESUMO
PURPOSE: Trastuzumab has proven to improve the prognosis of HER2-positive breast cancer, but the information available about its administration for small tumors is still limited. Therefore, we assessed the use of adjuvant regimens with trastuzumab for the treatment of small HER2-positive breast cancer in routine clinical practice. METHODS: This observational study was conducted in patients with HER2-positive breast adenocarcinoma ≤1.5 cm who received trastuzumab-based adjuvant treatment in clinical practice. Clinical/histopathological data were retrieved from patients' medical charts. RESULTS: A total of 101 evaluable patients were enrolled (median age [range], 56.7 [49.0-64.8] years; ECOG 0, 98.0 %; ductal carcinoma, 88.1 %; lymph nodes N0, 79.2 %). Only five (5.0 %) patients received neoadjuvant treatment, while all patients underwent tumor surgery. Adjuvant trastuzumab was administered at a mean (±SD) dose of 5.9 ± 1.5 mg/kg/cycle, and mostly in a three-weekly schedule (89 [89.0 %] patients). The most frequent adjuvant therapy used with trastuzumab was chemotherapy (87 [86.1 %] patients), followed by radiotherapy (63 [62.4 %] patients) and hormone therapy (52 [51.5 %] patients). Chemotherapy regimens mainly included doxorubicin, cyclophosphamide and paclitaxel/docetaxel (n = 30), docetaxel and cyclophosphamide (n = 15), docetaxel and carboplatin (n = 13). Hormone therapy mainly included letrozole (n = 17) and tamoxifen (n = 17). Nine (8.9 %) patients reported trastuzumab-related adverse events; only one allergic reaction reached grade 3 toxicity. CONCLUSION: This study shows that trastuzumab-based adjuvant treatment of small HER2-positive breast cancer is mostly based on chemotherapy-mainly paclitaxel/docetaxel. Adjuvant administration of trastuzumab for small HER2-positive breast cancer seems to be similar to that used for larger tumors.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Trastuzumab/uso terapêutico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Estudos Transversais , Ciclofosfamida/administração & dosagem , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Nitrilas/administração & dosagem , Paclitaxel/administração & dosagem , Receptor ErbB-2/genética , Tamoxifeno/administração & dosagem , Taxoides/administração & dosagem , Triazóis/administração & dosagemRESUMO
The solvatochromic behavior of sulfamethoxazole (SMX) was investigated using UV-vis spectroscopy and DFT methods in neat and binary solvent mixtures. The spectral shifts of this solute were correlated with the Kamlet and Taft parameters (α, ß and π(*)). Multiple lineal regression analysis indicates that both specific hydrogen-bond interaction and non specific dipolar interaction play an important role in the position of the absorption maxima in neat solvents. The simulated absorption spectra using TD-DFT methods were in good agreement with the experimental ones. Binary mixtures consist of cyclohexane (Cy)-ethanol (EtOH), acetonitrile (ACN)-dimethylsulfoxide (DMSO), ACN-dimethylformamide (DMF), and aqueous mixtures containing as co-solvents DMSO, ACN, EtOH and MeOH. Index of preferential solvation was calculated as a function of solvent composition and non-ideal characteristics are observed in all binary mixtures. In ACN-DMSO and ACN-DMF mixtures, the results show that the solvents with higher polarity and hydrogen bond donor ability interact preferentially with the solute. In binary mixtures containing water, the SMX molecules are solvated by the organic co-solvent (DMSO or EtOH) over the whole composition range. Synergistic effect is observed in the case of ACN-H2O and MeOH-H2O, indicating that at certain concentrations solvents interact to form association complexes, which should be more polar than the individual solvents of the mixture.
Assuntos
Elétrons , Modelos Moleculares , Teoria Quântica , Solventes/química , Sulfametoxazol/química , Absorção Fisico-Química , Acetonitrilas/química , Dimetil Sulfóxido/química , Dimetilformamida/química , Etanol/química , Espectrofotometria Ultravioleta , TermodinâmicaRESUMO
Stoichiometry and apparent stability constant (K(C)) of the complex formed between Al(III) and 3-hydroxyflavone were determined in methanol and water-methanol mixtures (% water w/w: 3.11; 6.15; 10.4; 15.2; 19.9 and 25.3) by UV-vis spectroscopy at 25.0°C and constant ionic strength (0.05 M, sodium chloride). Stoichiometry of the complex (1:2, metal:ligand) is not modified with an increase in water percentage in the analyzed interval. The value of K(C) in methanol is greater than in the binary solutions. The effects of changing solvent composition on K(C) data were explained by linear solvation free energy relationships using the solvatochromic parameter of Kamlet and Taft (α, ß and π(*)). Multiple linear regression analysis indicates that the hydrogen bond donating ability (α) of the solvent and non-specific interactions (π(*)) play an important role in the degree of occurrence of the reaction. The effect of temperature on K(C) was also analyzed by assessing standard entropy and enthalpy variations of the reaction in methanol. Finally, the structure of the complex was investigated using FTIR spectroscopy and DFT calculations. The ligand exhibits small structural changes upon complexation, localized on the chelating site. The calculated vibrational frequencies of the complex were successfully compared against the experimental values.
Assuntos
Alumínio/química , Flavonoides/química , Metanol/química , Água/química , Absorção , Cinética , Conformação Molecular , Concentração Osmolar , Soluções , Solventes/química , Espectrofotometria Infravermelho , Temperatura , VibraçãoRESUMO
The complexation of Al(III) by 2,4(OH)(2)-acetophenone in methanol and ethanol was investigated using spectroscopic methods (UV-vis) and theoretical procedures (DFT) in order to determine its stoichiometry and stability constant and to analyze the effect of temperature, ionic strength and solvent on the reaction rate. The stoichiometric composition of the complex is 1:1 and the stability constant in methanol is greater than in ethanol. The parameters obtained by the Arrhenius equation and the transition-state theory permitted to explain why the reaction proceeds more rapidly in EtOH. The reaction is favoured when the ionic strength and the reaction medium permittivity decrease. Taking into account the kinetic results and the theoretical calculations performed, a reaction mechanism in three steps is proposed that considers the interaction between ionic species of opposite unitary charge to generate the metal complex. In the formation of the complex, the aluminium atom interacts forming a covalent bond with the oxygen atom of the hydroxyl group of the ligand and its carbonyl group by means of a strong Coulombic interaction.
Assuntos
Acetofenonas/química , Alumínio/química , Etanol/química , Cinética , Ligantes , Metanol/química , Modelos Químicos , Concentração Osmolar , Solventes/química , Espectrofotometria Ultravioleta , TemperaturaRESUMO
The influence of temperature and solvent effects on the stability of the complex formed by two molecules of 1,2-dihydroxybenzene and one molecule of AlCl3 were experimentally and theoretically studied, by means of UV spectroscopic methods and Density Functional Theory methods. The changes of the stability constant with the temperature were analyzed using the van't Hoff equation, while the variations with the permittivity of the reaction medium were explained with an equation proposed by us. The experimental and theoretical data obtained allowed proving that the increase in the hydrogen-bond donor ability of the solvents favors a higher thermodynamic stability of the reactants with respect to the complex and, therefore a decrease in the corresponding stability constant. The non-planar structure proposed for the 2:1 ligand-metal complex is coherent with the small batochromic shift experimentally observed. In the complex molecule, the planes containing the phenyl rings are tilted by approximately 89 degrees with each other. It was concluded that the complexation reaction is an endothermic process in which the solvent-solute interactions play an essential role.