Abiraterone acetate in metastatic castration-resistant prostate cancer after chemotherapy. A retrospective “Real Life” analysis of activity and safety

Abiraterone acetate (AA) is a potent, selective androge (CYP17) biosynthesis inhibitor, which showed to improve overall survival (HR = 0.646) in mCRPC patients progressing after docetaxel. In this retrospective analysis we assessed the safety and efficacy of AA in patients affected with mCRPC progressing after chemotherapy, treated in the normal clinical practice, in several Italian Oncologic Units, after the approval of the drug from the Italian Drug Agency (AIFA)

Phase II study of liposomal doxorubicin, docetaxel and trastuzumab in combination with metformin as neoadjuvant therapy for HER2-positive breast cancer

Background:The aim of this study was to improve activity over single human epidermal growth factor receptor 2 (HER2)-blockade sequential neaodjuvant regimens for HER2-positive breast cancer, by exploiting the concomitant administration of trastuzumab, taxane and anthracycline, while restraining cardiac toxicity with use of liposomal doxorubicin, and by adding metformin, based on preliminary evidence of antitumor activity.Patients and methods:This multi-center, single-arm, two-stage phase II trial, assessed the safety and the activity of a new treatment regimen for HER2-positive, early or locally advanced breast cancer. Patients received six 21-day cycles of non-pegylated liposomal doxorubicin, 50 mg/m(2) intravenously (i.v.) on day 1, docetaxel, 30 mg/m(2) i.v. on days 2 and 9, trastuzumab, 2 mg/kg/week i.v. on days 2, 9, and 16 (with 4 mg/kg loading dose), in association with metformin 1000 mg orally twice daily. The primary endpoint was the rate of pathological complete response (pCR) in the breast and axilla (ypT0/is ypN0). A subgroup of patients performed a 3-deoxy-3-18F-fluorothymidine positron emission tomography (FLT-PET) at baseline and after one cycle.Results:Among 47 evaluable patients, there were 18 pCR [38.3%, 95% confidence interval (CI) 24.5-53.6%]. A negative estrogen-receptor status, high Ki67, and histological grade 3 were related with pCR, although only grade reached statistical significance. FLT-PET maximum standardized uptake value after one cycle was inversely related to pCR in the breast (odds ratio 0.29, 95% CI 0.06-1.30, p = 0.11). Toxicity included grade 3-4 neutropenia in 70% and febrile neutropenia in 4% of patients, grade 1-2 nausea/vomiting in 60%/38%, and grade 3 in 4%/2%, respectively, grade 1-2 diarrhea in 72%, and grade 3 in 6%. There were two cases of reversible grade 2 left-ventricular ejection-fraction decrease, and one case of sharp troponin-T increase.Conclusions:The concomitant administration of trastuzumab, liposomal doxorubicin, docetaxel, and metformin is safe and shows good activity, but does not appear to improve activity over conventional sequential regimens

Abiraterone acetate in metastatic castration-resistant prostate cancer after chemotherapy. A retrospective analysis of progression-free (PFS) and overall survival (OS) in the “Real Life”

Background: Abiraterone acetate (AA) is a potent, selective androgen (CYP17) biosynthesis inhibitor, which showed to improve overall survival (HR = 0.646) in mCRPC patients progressing after docetaxel. In this retrospective analysis we assessed the PFS and OS safety in patients affected with mCRPC progressing after chemotherapy, treated in the normal clinical practice, in several Italian Oncologic Units

Unraveling the safety of adjuvant radiotherapy in prostate cancer: impact of older age and hypofractionated regimens on acute and late toxicity - a multicenter comprehensive analysis

BackgroundThe objective of this study was to assess the impact of age and other patient and treatment characteristics on toxicity in prostate cancer patients receiving adjuvant radiotherapy (RT).Materials and methodsThis observational study (ICAROS-1) evaluated both acute (RTOG) and late (RTOG/EORTC) toxicity. Patient- (age; Charlson’s comorbidity index) and treatment-related characteristics (nodal irradiation; previous TURP; use, type, and duration of ADT, RT fractionation and technique, image-guidance systems, EQD2 delivered to the prostate bed and pelvic nodes) were recorded and analyzed.ResultsA total of 381 patients were enrolled. The median EQD2 to the prostate bed (α/β=1.5) was 71.4 Gy. The majority of patients (75.4%) were treated with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). Acute G3 gastrointestinal (GI) and genitourinary (GU) toxicity rates were 0.5% and 1.3%, respectively. No patients experienced >G3 acute toxicity. The multivariable analysis of acute toxicity (binomial logistic regression) showed a statistically significant association between older age (> 65) and decreased odds of G≥2 GI acute toxicity (OR: 0.569; 95%CI: 0.329-0.973; p: 0.040) and decreased odds of G≥2 GU acute toxicity (OR: 0.956; 95%CI: 0.918-0.996; p: 0.031). The 5-year late toxicity-free survival rates for G≥3 GI and GU toxicity were 98.1% and 94.5%, respectively. The only significant correlation found (Cox’s regression model) was a reduced risk of late GI toxicity in patients undergoing hypofractionation (HR: 0.38; 95% CI: 0.18-0.78; p: 0.008).ConclusionsThe unexpected results of this analysis could be explained by a “response shift bias” concerning the protective effect of older age and by treatment in later periods (using IMRT/VMAT) concerning the favorable effect of hypofractionation. However, overall, the study suggests that age should not be a reason to avoid adjuvant RT and that the latter is well-tolerated even with moderately hypofractionated regimens

Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

TIME ANALYSIS OF THE GIANT SLALOM TURN IN SNOWBOARDING

INTRODUCTION:Snowboarding is an increasingly popular sport, but it has been little studied so far, especially regarding the biomechanical characteristics (1). Most previous research concerned injury occurrence, the physiological profile of the snowboarding athletes (1) and dynamic variables characterizing the turn (2,3). Therefore, the aim of this study was to compare the turn technique of the snowboard giant slalom between elite and experienced recreational athletes, to improve the knowledge of performance factors and to provide suggestions to athletes and coaches. METHODS: Eight male snowboarders, four belonging to the Italian Snowboard National Team (EA, age 27\ub13.2y, height 1.80\ub10.10 m, mass 83.4\ub14.3 kg) and four experienced recreational athletes (RA, age 41.5\ub15.5 y, height 1.76\ub10.03 m, mass 89.0\ub112.2 kg) were analyzed during two performance on a snowboard slope (14 gates spaced at 21 m, 200m total descent). Eight wearable inertial and magnetic measurement units (APDM Opals, 128 Hz) were used for data collection. The sensors were fixed on sternum, sacrum, thigh, leg, toe of ski boot (right and left). Snowboarders were filmed when passing through the first 4 gates using a video camera (JVC full HD, 250hz) to compare the video recordings and the inertial sensor signal, and to define an algorithm to identifies automatically the transition of the gate and the change of the ski edge of all turns. These events were used to divide the turn in 4 phases: from change of ski edge to gate (T1) and from gate to change of ski edge (T2). Each event was identified for the backside-B and frontside-F turn, defining this way T1B, T2B, T1F, T2F respectively. RESULTS: Concerning time variables, EA showed shorter and more consistent times than RA in all turn phases (T1B 0.89\ub10.18s vs 0.99\ub10.11s, T2B 0.97\ub10.21s vs 1.53\ub10.50s, T1F 0.65\ub10.19s vs 1.23\ub10.3s, T2F 0.97\ub10.19s vs 1.31\ub10.22s), with significant differences (p<0.05) for all comparisons, with the exception of T1B. Also, the times of the total turn in B (0.92\ub10.19s vs 1.24\ub10.44s in EA and RA respectively) and in F (0.78\ub10.21s vs 1.25\ub10.24s in EA and RA respectively) were significantly shorter in EA than RA (p=0.03 and p=0.001 for B and F, respectively). T1 was shorter than T2 both in B and in F, but this difference was not statistically significant. CONCLUSION: As expected, EA completed all the phases of the turn more quickly than RA. This difference was noticeable during the F turn, especially in the T1 phase, more evidently than in B. In fact, as confirmed by the coaches of the Italian National Team, to perform an optimal F technique, highly developed technical skills are needed. Moreover, EA showed, for all variables, a lower variability and a higher repeatability than RA. The results of this study suggest that, in attempt to improve the performance, it is overall necessary to enhance F technical skills. 1) Vernillo et al., Frontiers in Physiology (2018) 2) Hirose et al., Procedia Engineering, (2012). 3) Kondo et al., Procedia Engineering, (2014)

Electrochemotherapy can be used as palliative treatment in patients with repeated loco-regional recurrence of squamous vulvar cancer: A preliminary study

Objective Electrochemotherapy (ECT) is an attractive treatment for solid cutaneous tumours with a good response rate (55-92%). No studies have evaluated ECT performed in vulvar cancer. The aim of our study was to evaluate the safety, local tumour efficacy and relief of symptoms of ECT treatment in patients affected by recurrence of squamocellular vulvar cancer (V-SCC) unsuitable for standard treatments. Methods We enrolled nine patients with histological diagnosis of recurrence of V-SCC. Intravenous bleomycin was injected under general sedation after an accurate mapping of all lesions and ECT was performed. Patients were reviewed after one, three and six months. Response to therapy was evaluated using RECIST criteria and quality of life (QoL) was evaluated via questionnaires. Results The median age was 84 years (range 80-90 years). The main location of recurrences was the vulva (87.5%). Multiple lesions were present in 25% of cases. No peri-operative complications were observed. Response to therapy was complete in 62.5% of patients, partial in 12.5%, no change was observed in 12.5% and progression of disease in 12.5% of patients respectively. Evaluation of symptoms showed a significant reduction of pain, bleeding, odour (p < 0.04) and urinary discomfort (p < 0.04). We observed two relapses at four and seven months after treatment. After nine months fifty percent of patients were alive. Conclusions Our preliminary study showed that ECT is a suitable procedure in elderly patients with loco-regional vulvar cancer relapses. ECT can be used as palliative therapy and the treatment relieves symptoms and improves QoL. \uc2\ua9 2013 Elsevier Inc. All rights reserved