e11633 Background: Treatment of locally advanced breast cancer (LABC) with anthracycline-based regimens have pathological complete response (pCR) of 10–15%, and with anthracyclin-taxane therapy have pCR 18–30%. Combined or sequential are both acceptable with the most important agents. Methods: We use a dose- dense regimen epirubicin and paclitaxel for 12 weeks to determine the effectiveness in the neoadjuvant setting could increase pCR and safety of the regimen. This phase II study investigated women with untreated locally advanced breast cancer assigned to receive epirrubicina 25 mg/m2 and paclitaxel 70 mg/m2 for twelve weeks. Results: 21 patients were enrolled at median follow up of eight months. The median age was 55 years old (28–67). The distribution by TNM was IIB (15%), IIIA (52%), IIIB (24%) y IIIC (9%) and tumor type was lobular (24%) and ductal (76%). The mean tumor size was 8 cm (5 -14 cm). Ninety percent completed twelve cycles of chemotherapy with a two hundred forty five cycles administered. In six patients had dose reduction by 10–20% in subsequent doses and one patient withdrawn from de study because of chemotherapy related toxicity. In 9 percent of patients we use G-SCF. Surgery was performed in 18 patients. Eleven patients (52%) achieved a clinical response (PR o CR) after twelve cycles. Complete pathological response and partial was 11% y 14%. Subset analysis of the effect of Independent predictors included receptor status, Her2 neu, tumor size, and histology was no statistically significant (p.68). Treatment was generally well tolerated. Grade 3/4 non-hematologic adverse events (neurotoxicity, nauseas and palmar plantar dysesthesia) events occurred in 5% of patients. No cardiac toxicity was found. Conclusions: Despite the small sample size, it was representative of our population of LABC. These data indicate that the combined regimen in dose-dense epirubicin and paclitaxel is a regimen with acceptable toxicity. However we have low percent of cPR, maybe we have a high percent of patients with stage IIIA and IIIB with large diameter of tumor size. No significant financial relationships to disclose.

Background: Heat shock protein 70, which protects cells from various forms of cellular stress, has gained significant attention as a potential therapeutic target in various malignancies. Methods: Here, pifithrin-μ, an effective dual inhibitor of HSP70 and p53, was employed to examine its anticancer activities and to analyze its possible effect for epithelialmesenchymal transition (EMT) in malignant mesothelioma cells. Results: MSTO-211HAcT cells, pre-adapted in medium containing lactic acid, showed more resistance to anticancer drugs, cisplatin and gemcitabine, when compared with their parental acid-sensitive MSTO-211H cells. Pifithrin-μ treatment induced cell death in a p53independent manner and developed EMT-like phenomenon, which was characterized by an elongated cell morphology, a decrease in the levels of epithelial cell markers, including E-cadherin, claudin 1 and b-catenin, and an increase in the level of mesenchymal markers, including vimentin and Snail, and increased migratory and invasive properties in MSTO-211HAcT cells. Moreover, p53 knockdown significantly enhanced the pifithrin-μmediated changes of critical EMT markers, migration and invasion, and anoikis resistance. Conclusions: Collectively, pifithrin-μ may contribute to malignant progression by promoting the EMT, at least in part, through the p53 inhibition, despite its preferential growth-inhibiting and apoptosis-promoting effects on MSTO-211HAcT cells under acidic extracellular environment.

Median PFS of patients who started pembrolizumab as firstline therapy was 10 months (95% CI 7.1-12.92); in those treated as secondline and thirdline, median PFS was 4.2 months (95% CI 3.12-5.27). AEs included asthenia grades 1-2 in 15.79%, arthralgia grades 1-2 in 13.16%, dermatitis in 7.89%, diarrhoea in 7.89%, hypothyroidism in 5.26%, pneumonitis in 5.26%, vomiting in 5.26%, anorexia in 5.26%, constipation in 5.26% and myalgia in 2.63%. Conclusion and relevance Median PFS in our study was similar to the results of Keynote-024 (pembrolizumab as firstline treatment) 10 versus 10.3 months and Keynote-010 (pembrolizumab in previously treated patients) 4.2 versus 3.9 months. Pembrolizumab was safe and well tolerated; the safety profile was similar to that described in clinical trials.