Aromatase inhibitors, efficacy and metabolic risk in the treatment of postmenopausal women with early breast cancer

The third-generation aromatase inhibitors (AIs), letrozole, anastrozole and exemestane, are becoming the first choice endocrine drugs for post-menopausal women with breast cancer, since they present greater efficacy when compared with tamoxifen in both adjuvant and metastatic setting. In particular, several large and well designed trials have suggested an important role for AIs in the adjuvant treatment of postmenopausal women with estrogen-receptor positive breast cancer either in the upfront, sequential or extended adjuvant mode. Overall, AIs are associated with a small but significant improvement in disease free survival. The expanding use of AIs in the treatment of early breast cancer means that individual patients will be exposed to the agents for longer durations, making it increasingly important to establish their long-term safety. This review focused on the effects of AIs on bone metabolism, serum lipids and cardiovascular risk. AIs have adverse effects on bone turnover with a reduction of bone mineral density and an increase in the rate of fragility fractures. With respect to tamoxifen AIs present lower thrombotic risk and a less favorable impact on lipid profile, whereas the true effects on cardiovascular risk still remain to be clarified. An adequate monitoring of bone mineral density (BMD) and lipid profile could be recommended for post-menopausal women candidate to AIs

Treating De novo metastatic castration sensitive prostate cancer with visceral metastases: an evolving issue

Visceral metastasis is widely considered a prognostic factor for overall survival of men with metastatic castration-sensitive prostate cancer (mCSPC) and has been historically managed with androgen deprivation therapy (ADT). More recently, this therapeutic scenario has been enriched by the possibility to integrate ADT with chemotherapy or novel androgen-signalling–targeted inhibitors. In order to define the effect of chemotherapy/androgen-signalling–targeted inhibitors plus ADT, we performed a pooled analysis on patients with mCSPC and visceral metastases revealing that survival was significantly improved in patients without visceral metastasis (HR=0.64 95%CI: 0.56-0.74; p<0.01) compared with men with visceral metastases (HR=0.68; 95%CI: 0.51-0.91; p<0.01). Although several limitations do not allow to draw definitive conclusions, our analysis confirms the efficacy of chemotherapy/androgen-signalling–targeted inhibitors in combination with ADT also in mCSPC with visceral metastases. In the absence of specific randomized controlled trials, symptoms, toxicity, cost, patients’ preference and clinical experience should guide the decision to add chemotherapy or androgen receptor-targeted therapy to ADT in patients with visceral metastases from mCSPC

Treating De novo metastatic castration sensitive prostate cancer with visceral metastases: an evolving issue

Visceral metastasis is widely considered a prognostic factor for overall survival of men with metastatic castration-sensitive prostate cancer (mCSPC) and has been historically managed with androgen deprivation therapy (ADT). More recently, this therapeutic scenario has been enriched by the possibility to integrate ADT with chemotherapy or novel androgen-signalling–targeted inhibitors. In order to define the effect of chemotherapy/androgen-signalling–targeted inhibitors plus ADT, we performed a pooled analysis on patients with mCSPC and visceral metastases revealing that survival was significantly improved in patients without visceral metastasis (HR=0.64 95%CI: 0.56-0.74; p<0.01) compared with men with visceral metastases (HR=0.68; 95%CI: 0.51-0.91; p<0.01). Although several limitations do not allow to draw definitive conclusions, our analysis confirms the efficacy of chemotherapy/androgen-signalling–targeted inhibitors in combination with ADT also in mCSPC with visceral metastases. In the absence of specific randomized controlled trials, symptoms, toxicity, cost, patients’ preference and clinical experience should guide the decision to add chemotherapy or androgen receptor-targeted therapy to ADT in patients with visceral metastases from mCSPC

Channel-aware routing for underwater wireless networks

Abstract-This paper presents a new cross layer routing protocol for underwater wireless sensor networks. The solution, termed CARP for Channel-aware Routing Protocol, exploits link quality information for cross layer relay determination. Nodes are selected as relays if they have a (recent) history of successful transmissions to their neighbors. CARP combines link quality with simple topology information (hop count), thus being able to route around connectivity voids and shadow zones. The protocol is also designed to take advantage of power control for selecting robust links. The performance of CARP has been evaluated through ns2-based simulations, and compared to the performance of two previously proposed routing protocols, namely, FBR and DBR. Our results show that CARP robust relay selection mechanism enables it to achieve throughput efficiency that is up to twice the throughput of FBR and almost three times that of DBR. CARP also obtains remarkable performance improvements over FBR and DBR with respect to end-to-end packet latency and energy consumption. Index Terms-Underwater acoustic networks, cross layer design, MAC and routing protocols

Is there still a place for vinorelbine in advanced metastatic castration resistant prostate cancer?

The aim of this paper was to evaluate the activity and tolerability of oral vinorelbine in patients with advanced castration resistant prostate cancer (CRPC) who progressed after a minimum of three lines including: abiraterone acetate, docetaxel, cabazitaxel, and enzalutamide.Treatment consisted of weekly oral vinorelbine 60\u200amg/m. Chemotherapy was administered until disease progression or unacceptable toxicity.Twenty-six patients received vinorelbine: their median age was 74 years (range 58-84 years). Twenty-four (92.3%) patients had bone metastases. A decrease in PSA levels 6550% was observed in 2 patients (7.7%). Among the subjects who were symptomatic at baseline, pain was reduced in 3 patients (13.6%) with a significant decrease in analgesic use. Median progression-free survival was 9 weeks (95% CI: 7 to 11) and median overall survival was 17 weeks (95% CI: 12 to 22). Treatment was well tolerated, and no grade 4 toxicities were observed.Our findings do not suggest the use of oral vinorelbine on a weekly schedule, in CRPC heavily pre-treate

The role of bevacizumab in solid tumours: A literature based meta-analysis of randomised trials

BACKGROUND: Bevacizumab is a humanised monoclonal antibody which blocks the binding of circulating vascular endothelial growth factor to its receptors. To date, the Food and Drug Administration has approved bevacizumab for the treatment of several solid tumours. To assess the impact of bevacizumab-based regimens on outcome in these advanced solid tumour types, we performed a meta-analysis. We included all of the randomised trials (phase II or III) where bevacizumab was tested in the first line setting compared with a control arm, including chemotherapy, placebo or other anti-neoplastic agents. METHODS: A literature-based meta-analysis of randomised controlled trials (RCTs) in accordance with the preferences for reported items in systematic reviews and meta-analyses guidelines were undertaken. The primary end-point considered was overall survival (OS). The secondary end-points were progression-free survival (PFS) time, response rate and safety. A subgroup analysis was performed to highlight any differences between studies in different tumour types for all end-points. RESULTS: The pooled analysis from RCTs on bevacizumab-based regimens revealed significantly increased OS (hazard ratio [HR] for death 0.92, 95% confidence interval [CI]: 0.88-0.95; P < 0.0001), PFS (HR: 0.72, 95% CI: 0.67-0.78; P < 0.00001) and response rate (risk ratio: 1.38, 95% CI: 1.27-1.50; P < 0.00001) compared to control arm in solid tumours overall and in colorectal, lung, ovarian and renal cancer as single indications. However, notably, no effect on survival was seen in breast cancer. CONCLUSION: This study confirmed that bevacizumab-based regimens result in a significant effect on survival and response in advanced colorectal, lung, ovarian and kidney cancer. In cancers where bevacizumab failed overall as in breast cancer, a dedicated biomarkers analysis is warranted to select the proper subgroup of patient that might have the adequate clinical benefi

Association between neutropenia and response to ramucirumab and paclitaxel in patients with metastatic gastric cancer

PURPOSE: The aim of this study was to evaluate if the occurrence of neutropenia is correlated with response to ramucirumab plus paclitaxel for metastatic gastric cancer.METHODS: This is a retrospective study of patients treated with ramucirumab plus paclitaxel.RESULTS: Fifty-three patients were evaluated. Among these, 10 patients (26.5%) developed grade ≥3 neutropenia. Patients with grade ≥3 neutropenia reported a progression-free survival of 6.6 months (95% confidence interval 3.3-8.4) and overall survival of 11 months (95% confidence interval 5.9-13.1) vs. 4.4 months (95% confidence interval 3.9-5.2) and 8.7 months (95% confidence interval 7.8-10.1) respectively in patients' group with lower grade events.CONCLUSION: Our analysis seems to suggest that the occurrence of neutropenia predicts response to treatment with ramucirumab and paclitaxel.</p

Clinical outcomes and safety of patients treated with NAb-Paclitaxel plus Gemcitabine in metastatic pancreatic cancer:the NAPA study

BACKGROUND: The phase III MPACT trial demonstrated the superiority of gemcitabine (Gem) combined with Nab-paclitaxel (Nab-P) versus gemcitabine alone in previously untreated patients with metastatic pancreatic ductal adenocarcinoma (PDAC). The purpose of this study was to evaluate the effect of Gem/Nab-P in routine clinical practice.METHODS: From January 2015 to December 2018, patients with metastatic PDAC receiving first-line treatment with a combination of gemcitabine and Nab-paclitaxel were included in a multicentre retrospective observational study. Exploratory analyses of efficacy, and prognostic and predictive markers, were performed.RESULTS: The cohort comprised 115 patients (median age 65 [range 50-84] years) with good performance status (ECOG PS 0-1). The median overall survival (OS) was 11 months (95 % CI; 9-13) and the median progression free survival (PFS) was 6 months (95 % CI 5-7). Partial response and stable disease were achieved in 44 and 30 patients respectively, yielding an overall disease control rate (DCR) of 64.3%. Grade 3-4 haematological toxicity frequency was 22.61% for neutropenia, 5.22% for anaemia and 3.48% for thrombocytopenia. Grade 3 asthenia was recorded in 2.61% of patients. No grade 4 nonhaematological events were reported. Dose reduction was necessary in 51.3 % of the patients.CONCLUSIONS: Our results confirm the efficacy and safety of a first line regimen comprising gemcitabine and Nab-paclitaxel in metastatic PDAC in a real-life population.</p

Bevacizumab and Weekly Docetaxel in Patients with Metastatic Castrate-Resistant Prostate Cancer Previously Exposed to Docetaxel

Background. The aim of this paper was to evaluate the activity and tolerability of docetaxel (D) and bevacizumab (Bev) in patients with metastatic castrate-resistant prostate cancer (CRPC) previously exposed to D. Methods. Treatment consisted of D 30 mg/m(2) i.v. for four consecutive weekly administrations followed by a 2-week rest interval, in addition to Bev 5 mg/kg i.v. every 2 weeks. Results. Forty-three patients were enrolled: a PSA response was observed in 27 patients (62.7%, 95% CI: 0.41 to 0.91), and a palliative response was achieved in 31 patients (72.1%, 95%CI: 0.48 to 1.02). After a median followup of 11.3 months, only five patients had died. The regimen was generally well tolerated. Conclusion. Weekly D + biweekly Bev seems to be an effective and well-tolerated treatment option for patients with metastatic CRPC previously exposed to D-based chemotherapy