Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma: a retrospective analysis.

Neoadjuvant chemotherapy is being increasingly used in the treatment of breast carcinoma. We performed a single-center retrospective analysis of the results of neoadjuvant therapy in 376 breast carcinoma patients treated with three different regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER)-2 was determined immunohistochemically. Pathological response was determined in 318 patients. Pathological complete response (pCR) was observed in 18% of patients. The pCR rate was significantly higher in patients treated with DD regimen (22 vs. 13%) and younger than 55 years (23 vs. 13%). The pCR rate was higher in patients with triple negative (TN) tumors (43%) and tumors over-expressing HER-2 (HER-2+; 28%) compared to patients with ER- or PR-positive tumors not expressing HER-2 (ER/PR+HER-2-; 6%). In patients with TN tumors pCR rate was significantly higher after treatment with DD AC-P compared to AT (61 vs. 22%, p=0.005). pCR was associated with significantly improved relapse-free survival (RFS) and overall survival (OS), but when analysis was performed based on tumor phenotype, the difference was significant only in patients with TN tumors. In multivariate analysis, pCR, stage, and ER expression were significant predictors of RFS, while pCR, stage, ER and DD regimen were significant predictors of OS. In conclusion, present data indicate superiority of a DD regimen in obtaining pCR in patients with breast carcinoma treated with neoadjuvant chemotherapy. The difference in efficacy is due mostly to markedly higher pCR rate in patients with TN tumors.

Systemic inflammatory response syndrome (SIRS) in serious chest injuries: is a pharmacological blockade effective?

PURPOSE: There has been an ongoing increase in the frequency and severity of blunt chest injuries. Their rather high lethality is caused by the injury alone as well as by the following systemic inflammatory response. The aim of the study is to verify the efficacy of the pharmacological blockade of the systemic inflammatory response syndrome (SIRS) in serious blunt chest injuries, and to identify whether the administration of indomethacin as a cyclooxygenase inhibitor could prevent a multiorgan dysfunction (MODS) and a multiorgan failure (MOF). METHODS: Patients were divided into 4 Groups according to trauma severity--injury severity score (ISS) and into two subgroups--an indomethacin subgroup where patients received indomethacin together with standard therapy, and a non-indomethacin subgroup. RESULTS: Eighty-four patients were included in the study and 33 patients were given indomethacin. In Groups III and IV there was a later increase in inflammatory markers in patients treated with indomethacin. The elevation of inflammatory markers and the period of mechanical ventilation support in patients treated with indomethacin were shorter in Groups II and III. Seven (8.3%) patients died. Six of the seven dead patients were from the non-indomethacin subgroup. MOF was the cause of death in two patients in the non-indomethacin subgroup and in one patient in the indomethacin subgroup. CONCLUSION: The results obtained during the first 20 months of the study imply that a certain number of patients with serious blunt chest trauma could benefit from indomethacin administration.