“Oxaliplatin plus high dose folinic acid and 5-fluoruracil i.v. bolus (OXAFAFU) versus irinotecan plus high dose folinic acid and 5-fluoruracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: Southern Italy Cooperative Oncology Group trial 0103”

PURPOSE: The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma. PATIENTS AND METHODS: Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)]. RESULTS: Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU. CONCLUSIONS: OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients

Tumour-associated macrophages correlate with microvascular bed extension in colorectal cancer patients

Tumour-associated macrophages (TAMs) represent pivotal components of tumour microenvironment promoting angiogenesis, tumour progression and invasion. In colorectal cancer (CRC), there are no conclusive data about the role of TAMs in angiogenesis-mediated tumour progression. In this study, we aimed to evaluate a correlation between TAMs, TAM immunostained area (TAMIA) microvascular density (MVD), endothelial area (EA) and cancer cells positive to VEGF-A (CCP-VEGF-A) in primary tumour tissue of locally advanced CRC patients undergone to radical surgery. A series of 76 patients with CRC were selected and evaluated by immunohistochemistry and image analysis. An anti-CD68 antibody was employed to assess TAMs and TAMIA expression, an anti-CD34 antibody was utilized to detect MVD and EA expression, whereas an anti-VEGF-A antibody was used to detect CCP-VEGF-A; then, tumour sections were evaluated by image analysis methods. The mean ± S.D. of TAMs, MVD and CCP-VEGF-A was 65.58 ± 21.14, 28.53 ± 7.75 and 63% ± 37%, respectively; the mean ± S.D. of TAMIA and EA was 438.37 ± 124.14μ2 and 186.73 ± 67.22μ2, respectively. A significant correlation was found between TAMs, TAMIA, MVD and EA each other (r ranging from 0.69 to 0.84; P ranging from 0.000 to 0.004). The high level of expression of TAMs and TAMIA in tumour tissue and the significant correlation with both MVD and EA illustrate that TAMs could represent a marker that plays an important role in promoting angiogenesis-mediated CRC. In this context, novel agents killing TAMs might be evaluated in clinical trials as a new anti-angiogenic approach

Efficacy and safety of T-DM1 in the 'common-practice' of HER2+ advanced breast cancer setting: a multicenter study

Ado-trastuzumab emtansine (T-DM1) is an antibody-drug conjugate approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive, metastatic breast cancer (mBC). The aim of this 'field-practice' study was to investigate the efficacy and safety of T-DM1, focusing on treatment line, previous lapatinib treatment and patterns of metastasis. Three hundred and three patients with HER2-positive mBC who received T-DM1 were identified by reviewing the medical records of 24 Italian Institutions. One hundred fourty-nine (49%) and 264 (87%) had received prior hormonal treatment and/or anti-HER2 targeted therapy, respectively. Particularly, 149 patients had been previously treated with lapatinib. The objective response rate (ORR) was 36.2%, and 44.5% when T-DM1 was administrated as second-line therapy. Considering only patients with liver metastases, the ORR was 44.4%. The median progression-free survival (PFS) was 7.0 months in the overall population, but it reached 9.0 and 12.0 months when TDM-1 was administered as second- and third-line treatment, respectively.In conclusion, in this 'real-word' study evaluating the effects of T-DM1 in patients with HER2-positive mBC who progressed on prior anti-HER2 therapies, we observed a clinically-relevant benefit in those who had received T-DM1 in early metastatic treatment-line and in subjects previously treated with lapatini

Essential Oils from Southern Italian Aromatic Plants Synergize with Antibiotics against <i>Escherichia coli</i>, <i>Pseudomonas aeruginosa</i> and <i>Enterococcus faecalis</i> Cell Growth and Biofilm Formation

The spread of antibiotic-resistant pathogens has prompted the development of novel approaches to identify molecules that synergize with antibiotics to enhance their efficacy. This study aimed to investigate the effects of ten Essential Oils (EOs) on the activity of nine antibiotics in influencing growth and biofilm formation in Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis. The effects of the EOs alone and in combination with antibiotics on both bacterial growth and biofilm formation were analyzed by measuring the MIC values through the broth microdilution method and the crystal violet assay, respectively. All EOs inhibited the growth of E. coli (1.25 ≤ MIC ≤ 5 mg/mL) while the growth of P. aeruginosa and E. faecalis was only affected by EOs from Origanum vulgare, (MIC = 5 mg/mL) and O. vulgare (MIC = 1.25 mg/mL) and Salvia rosmarinus (MIC = 5 mg/mL), respectively. In E. coli, most EOs induced a four- to sixteen-fold reduction in the MIC values of ampicillin, ciprofloxacin, ceftriaxone, gentamicin, and streptomycin, while in E. faecalis such a reduction is observed in combinations of ciprofloxacin with C. nepeta, C. bergamia, C. limon, C. reticulata, and F. vulgare, of gentamicin with O. vulgare, and of tetracycline with C. limon and O. vulgare. A smaller effect was observed in P. aeruginosa, in which only C. bergamia reduced the concentration of tetracycline four-fold. EO-antibiotic combinations also inhibit the biofilm formation. More precisely, all EOs with ciprofloxacin in E. coli, tetracycline in P. aeruginosa, and gentamicin in E. faecalis showed the highest percentage of inhibition. Combinations induce up- and down-methylation of cytosines and adenines compared to EO or antibiotics alone. The study provides evidence about the role of EOs in enhancing the action of antibiotics by influencing key processes involved in resistance mechanisms such as biofilm formation and epigenetic changes. Synergistic interactions should be effectively considered in dealing with pathogenic microorganisms

Sorafenib: 10 years after the first pivotal trial

Sorafenib is an oral multikinase inhibitor with anticancer activity against a wide spectrum of cancers. It is currently approved for the treatment of patients with hepatocellular carcinoma, advanced renal cell carcinoma or progressive, locally advanced or metastatic differentiated thyroid carcinoma. In this review, we present a number of studies that investigated the efficacy and safety of sorafenib in these settings. We also discuss the perspectives on the use of this molecule, including the role of sorafenib as comparator for the development of new drugs, the combination of sorafenib with additional therapies (such as transarterial chemoembolization for hepatocellular carcinoma) and the use of this treatment in several other advanced refractory solid tumors