Activity of megestrol acetate in postmenopausal women with advanced breast cancer after nonsteroidal aromatase inhibitor failure: a phase II trial.

BACKGROUND: As novel treatments carry substantial price tags and are mostly cost-prohibitive in low- and middle-income countries, there is an urgent need to develop alternatives, such as off-patent drugs. Megestrol acetate (MA) has a longstanding history in the treatment of breast cancer, but recently it is being used less often due to the advent of newer agents. PATIENTS AND METHODS: This two-stage phase II trial evaluated the antitumor activity and toxicity of MA in postmenopausal women with hormone-sensitive advanced breast cancer who had experienced disease progression on a third-generation nonsteroidal aromatase inhibitor (NSAI). Eligible patients had metastatic breast cancer treated with a NSAI with at least 6-month progression-free survival (PFS), or relapse after ≥1 year on adjuvant NSAI. Patients received MA at a single daily oral dose of 160 mg. Primary end point was clinical benefit rate (CBR). RESULTS: Forty-eight patients were enrolled. The CBR was 40% [95% confidence interval (CI) 25% to 55%], and the median duration of clinical benefit was 10.0 (95% CI 8.0-14.2) months. The median PFS was 3.9 (95% CI 3.0-4.8) months. The most common grade 3 adverse events were anemia (2%), dyspnea (2%), fatigue (2%), musculoskeletal pain (4%), deep vein thrombosis (10%), and weight gain (2%). CONCLUSIONS: This is the first study to prospectively evaluate the efficacy and safety of MA in postmenopausal women with hormone-sensitive disease progressing on a NSAI. MA has demonstrated activity and acceptable tolerability in this setting, and therefore remains a reasonable treatment option in a cost-sensitive environment. These results also provide the background for further evaluation of progestins in the treatment of breast cancer. CLINICAL TRIALS: local trial number, related to the approval by the IRB: CEP 108/06.

Redução da variabilidade da freqüência cardíaca em indivíduos de meia-idade e o efeito do treinamento de força / Reduction of heart rate variability in middle-aged individuals and the effect of strength training

OBJETIVO: Investigar a modulação autonômica exercida sobre o nodo sinusal, por meio da análise da variabilidade da freqüência cardíaca (VFC), em indivíduos jovens e de meia-idade (MI), bem como os efeitos de um programa de treinamento de força resistência sobre tal modulação nos indivíduos de meia-idade. MÉTODO: Trinta e dois homens sadios, sedentários e não-tabagistas, sendo 10 jovens (22,2 ± 1,5 anos) e 22 de MI (49,3 ± 5,3 anos), foram submetidos à aquisição do sinal de eletrocardiograma para análise da VFC no domínio do tempo. Os indivíduos de MI foram divididos em dois grupos: experimental (n= 12) e controle (n= 10). Os indivíduos do grupo experimental foram inseridos em um programa de treinamento de força com duração de três meses. A análise dos dados foi realizada por meio dos testes de Wilcoxon e Mann-Whitney (p< 0,05). RESULTADOS: O grupo MI apresentou redução significativa, em comparação ao jovem, de todas as variáveis utilizadas para a investigação da VFC (SDNN= 33,4 vs. 49,7ms; RMSSD= 29,9 vs. 49,5ms; pNN50= 6,5 vs. 27 por cento). O treinamento promoveu aumento significativo da força e resistência muscular em todos os grupamentos musculares e aumento não significativo das variáveis SDNN (33,4 vs. 37,6ms), RMSSD (30,2 vs. 31,3ms) e pNN50 (7,5 vs. 11,4 por cento). CONCLUSÕES: Os achados deste estudo confirmam que o aumento da idade provoca alteração na modulação autonômica exercida sobre o nodo sinusal, retratada por uma diminuição da VFC em indivíduos de MI, que não foi modificada de maneira significativa pelo tipo de treinamento físico estudado.

OBJECTIVE: To investigate autonomic modulation of the sinus node, by analyzing heart rate variability (HRV) among young and middle-aged individuals, and to assess the effect of an endurance strength training program on this modulation among middle-aged individuals. METHOD: Thirty-two healthy nonsmoking men with sedentary lifestyles, of whom 10 were young (22.2 ± 1.5 years) and 22 were middle-aged (49.3 ± 5.3 years), underwent electrocardiogram signal acquisition for time-domain HRV analysis. The middle-aged individuals were divided into two groups: experimental (n= 12) and control (n= 10). The individuals in the experimental group were enrolled in a strength training program lasting three months. The data analysis was carried out using the Wilcoxon and Mann-Whitney tests (p< 0.05). RESULTS: The middle-aged group presented significant reductions (in relation to the young group) for all the variables used in investigating HRV (SDNN= 33.4 vs. 49.7 ms; RMSSD= 29.9 vs. 49.5 ms; pNN50= 6.5 vs. 27 percent). The training caused a significant increase in muscle strength and endurance for all muscular groups and non-significant increases in the variables SDNN (33.4 vs. 37.6 ms), RMSSD (30.2 vs. 31.3 ms) and pNN50 (7.5 vs. 11.4 percent). CONCLUSIONS: The findings from this study confirm that increased age causes alteration to the autonomic modulation of the sinus node, as demonstrated by reduced HRV in middle-aged individuals, which was not significantly modified by the type of physical training studied.

Susceptibility of Giardia lamblia to Hovenia dulcis extracts.

Giardia lamblia is the causative agent of giardiasis, a common parasitic infection of the human and animal digestive tract. Although several drugs have been available to treat this infection, they present unpleasant side effects or cytotoxicity. In order to find a more natural treatment for the disease, we analyzed the effects of the methanolic extract and three fractions obtained from Hovenia dulcis Thunb. (Rhamnaceae) leaves on G. lamblia. Comparing all fractions, dichloromethane was more efficient in reducing Giardia growth. The exposition of G. lamblia to this fraction lead to degenerations in the surface, modifications in the cell shape and alterations in the localization of nuclei. Besides that, the adhesion of G. lamblia was also altered. Experiments revealed that the obtained fraction did not present cytotoxic effects in mammalian cells. In summary, dichloromethane fraction has strong antigiardial effects and could become an important new substance for the treatment of giardiasis.