In this trial, neither capecitabine nor gemcitabine added to an anthracycline Semagacestat taxane based chemotherapy regimen improved the rates of clinical or pathological response, despite the suggestive results that have been seen in patients with metastatic breast cancer. Thus, it appears unlikely that these drugs would add much benefit in the adjuvant setting. Indeed, our results confirm the largely negative results of several trials of adjuvant therapy with these drugs,21 23 supporting our hypothesis that trials of neoadjuvant therapy serve as better predictors of adjuvant benefits than studies of metastatic disease. The addition of bevacizumab resulted in a modest but significant increase in the rate of pathological complete response in the breast, but the rate of pathological complete response in the breast and nodes was not significantly increased, which may indicate that this drug will have a lesser effect on patient outcomes.
Moreover, adding bevacizumab increased a number omeprazole clinica rial of toxic effects. Left ventricular dysfunction was noted as a serious concern in a recent meta analysis of bevacizumab therapy in patients with metastatic breast cancer.24 Left ventricular function and wound complications are being closely monitored posaconazole structure in patients receiving adjuvant bevacizumab therapy as well as in the long termfollow up of these patients. It is unclear why the greatest benefit from adding an antiangiogenic agent was seen in patients with hormone receptor positive tumors, in contrast to the findings in the GeparQuinto trial, reported by von Minckwitz et al.
elsewhere in this issue of the Journal,25 HDAC agonist in which the benefit was confined to patients with hormone receptor negative tumors. The disparity in the results of the two trials may be related to differences in the inclusion criteria and the study design, particularly the inclusion in the GeparQuinto trial of patients with more advanced disease, a different sequencing of drug regimens in the GeparQuinto trial than that in our trial, and the withdrawal from the GeparQuinto study of patients who did not have a response to the initial four cycles of treatment.25 The benefit of bevacizumab in our study also tended to be seen in patients with a high tumor grade, a finding that was also observed in the GeparQuinto study.
The increased rate of pathological complete response in patients with hormone receptor positive tumors is encouraging, since this group tends to have ecology low rates of pathological complete response with chemotherapy. The addition of an antimetabolite in two thirds of our patients, with a concomitant decrease in the dose of docetaxel, might account for the disproportionate effect of adding bevacizumab in the docetaxel capecitabine and docetaxel gemcitabine groups. The effect of adding bevacizumab in the NSABP B 40 trial was less dramatic than was the effect of adding docetaxel in the NSABP B 27 trial, so it is not clear whether the neoadjuvant effect of bevacizumab would translate into a substantial benefit to patients. However, the groups that were randomly assigned to bevacizumab in our trial also received bevacizumab postoperatively, so the potential for bevacizumab to improve the outcomes should be clarified when the results with respect to diseasefree survival and overall survival.
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