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PURPOSE: TAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor-copositive metastatic breas...
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PURPOSE: TAnDEM is the first randomized phase III study to combine a hormonal agent and trastuzumab without chemotherapy as treatment for human epidermal growth factor receptor 2 (HER2)/hormone receptor-copositive metastatic breast cancer (MBC). PATIENTS AND METHODS: Postmenopausal women with HER2/hormone receptor-copositive MBC were randomly assigned to anastrozole (1 mg/d orally) with or without trastuzumab (4 mg/kg intravenous infusion on day 1, then 2 mg/kg every week) until progression. The primary end point was progression-free survival (PFS) in the intent-to-treat population. Results Overall, 103 patients received trastuzumab plus anastrozole; 104 received anastrozole alone. Patients in the trastuzumab plus anastrozole arm experienced significant improvements in PFS compared with patients receiving anastrozole alone (hazard ratio = 0.63; 95% CI, 0.47 to 0.84; median PFS, 4.8 v 2.4 months; log-rank P = .0016). In patients with centrally confirmed hormone receptor positivity (n = 150), median PFS was 5.6 and 3.8 months in the trastuzumab plus anastrozole and anastrozole alone arms, respectively (log-rank P = .006). Overall survival in the overall and centrally confirmed hormone receptor-positive populations showed no statistically significant treatment difference; however, 70% of patients in the anastrozole alone arm crossed over to receive trastuzumab after progression on anastrozole alone. Incidence of grade 3 and 4 adverse events was 23% and 5%, respectively, in the trastuzumab plus anastrozole arm, and 15% and 1%, respectively, in the anastrozole alone arm; one patient in the combination arm experienced New York Heart Association class II congestive heart failure. CONCLUSION: Trastuzumab plus anastrozole improves outcomes for patients with HER2/hormone receptor-copositive MBC compared with anastrozole alone, although adverse events and serious adverse events were more frequent with the combination.
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Ageing is an inevitable biological process characterized by a general decline in various physiological functions. DHEA and DHEAS levels are maximal between the second and third life decades, then start to decline 2% per year, leav...
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Ageing is an inevitable biological process characterized by a general decline in various physiological functions. DHEA and DHEAS levels are maximal between the second and third life decades, then start to decline 2% per year, leaving a residual of 10-20% of the peak production by the eighth decade. Erythrocytes are exposed to frequent oxidative stress due to the oxygen radicals continuously generated by haemoglobin auto-oxidation. We investigated DHEA chronic (10 mg/kg, subcutaneously, for 5 weeks) effects over oxidative stress markers in erythrocytes of male Wistar rats of 3, 13 and 18 month-old. In the 13 month-old group, we found increased lipid peroxidation (LPO), superoxide dismutase (SOD), glutathione-S-transferase and catalase activities when compared to the other age groups. DHEA produced a marked increase in LPO of 13 month-old group when compared to its control. DHEA exerted this pro-oxidant effects in all ages studied, especially in age 13 month-old. It seems that at 13 month-old there would be an important depletion of some specific anti-oxidant in order to determine such susceptibility to DHEA effects. Since this approach allows a minimally invasive assessment, it would be useful as a routine method in human clinical studies investigating DHEA effects during the ageing process.
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The secretion of DHEA-synthesized mainly in the adrenal cortex-increases in the postnatal aging, peaks in the twenties and decreases with age afterwards. Exogenous DHEA can exert a dual effect depending on dose and on tissue. Akt ...
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The secretion of DHEA-synthesized mainly in the adrenal cortex-increases in the postnatal aging, peaks in the twenties and decreases with age afterwards. Exogenous DHEA can exert a dual effect depending on dose and on tissue. Akt is a serine/threonine kinase whose activity has been seen as an interventional approach for cardiomyopathic damage resulting from aging changes. In order to evaluate DHEA effects over myocardial Akt protein expression associated to oxidative stress markers during aging, male Wistar rats (3 and 18 months) were assigned into two groups: control or DHEA (10mg/kg, subcutaneously, for 5 weeks). In the aged group, we found increased lipid peroxidation and glutathione-S-transferase activity. DHEA produced an increase in p-Akt protein expression and a decrease in SOD activity in both ages. Akt pathway activation might be related to changes in oxidative stress parameters according to age.
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