Activity of eribulin mesylate in brain metastasis from breast cancer. a stone in a pond?

Background: Brain metastases develop in approximately 10-25% of patients with metastatic breast cancer (MBC) and are associated with a very poor prognosis. Case Report: We report the case of a 40-year-old woman with MBC and associated lung, bone, liver, and brain metastases, who experienced a time to progression of several months with eribulin after whole-brain radiotherapy (WBRT), 2 lines of chemotherapy, and 1 line of hormonal therapy, maintaining a good toxicity profile. Discussion: Eribulin, in association with local treatment such as WBRT, can be well tolerated and effective in achieving a long progression-free survival and a good control of brain metastases in patients with MBC who have received multiple lines of treatment. The vascular remodeling properties of eribulin, combined with brain radiotherapy, might facilitate the passage of eribulin across the blood brain barrier, improving brain response. Conclusion: Our anecdotal experience suggests that eribulin may have a potentially beneficial effect on brain metastases while maintaining a good systemic control of the disease in patients with MBC

The course of cancer related fatigue up to ten years in early breast cancer patients. What impact in clinical practice?

Little is known about the cancer related fatigue (CRF) along cancer course and risk factors that could predict CRF development and persistence in breast cancer (BC) survivors. This prospective study detected incidence, timing of onset, duration of CRF, impact on QoL and psychological distress. Seventy-eight early BC patients, undergoing chemotherapy (CT) followed or not by hormonal therapy were assessed for QoL and psychological distress by EORTC QLQC30 and HADs questionnaires. Fatigue was investigated with mix methods, structured interview and psychometric measures. A qualitative analysis was added to assess the behavioral pattern of CRF. Low fatigue levels were identified after surgery (9%), increasing during (49%) and at the end of CT (47%), maintaining after 1 year (31%) and declining up to ten years of follow-up. Prevalence of CRF was higher at the end of CT and lower at follow-up. At the end and after 1 and 2 years from CT, persistence of CRF was associated to anxiety in 20%, 11% and 5% and to depression in 15%, 10% and 5% respectively. A relationship between CRF and psychological distress was observed; patients presenting depression and anxiety before CT were at higher risk for fatigue onset at a later period. A relationship between fatigue and QoL was noted at the end of CT. Our study shows the fatigue timely trend in early BC patients from surgery, CT and follow-up. Identification of biological, psychological, social predictor factors related to fatigue could be helpful for early interventions in patients at higher risk of developing fatigue

The other side of p53

n/

Impressive long-term response with pertuzumab and trastuzumab in HER2-positive breast cancer with brain metastasis

This is a case report of a 40-year-old woman who, after conservative breast cancer treatment, developed a HER2 positive solitary brain metastasis in the left temporal lobe, without extracranial disease. She underwent surgery resection followed by stereotactic radiotherapy and, because of early brain progression, she was submitted to the first line therapy with pertuzumab, trastuzumab and weekly paclitaxel. After six months of treatment, a brain magnetic resonance imaging revealed a complete disappearance of brain recurrence, which persisted for more than 24 months

Maintenance bevacizumab beyond first-line paclitaxel plus bevacizumab in patients with Her2-negative hormone receptor-positive metastatic breast cancer. Efficacy in combination with hormonal therapy

Background: Data on efficacy of bevacizumab (B) beyond first-line taxane -including regimen (BT) as first-line treatment are lacking. Although preclinical results that anti-angiogenic agents combined with hormonal therapy (HT) could be active, no clinical data exist about combination of maintenance Bevacizumab (mBev) with HT.Methods: Thirty-five patients who experienced a response after first-line BT, were given mBev at the dose of 15 mg/kg every 3 weeks. Among 30 pts with hormonal receptor-positive metastatic breast cancer (MBC), 20 (66.6%) received HT with mBev (mHTBev). Objective of the study was the outcome and safety of mBev and in two groups of patients receiving HT or not.Results: Complete response and partial response was achieved/maintained in 4 (11.4%) and 13 (37.1%) patients, respectively (overall response rate: 48.5%). Clinical benefit was obtained on 23 patients (65.7%). Median of mBev PFS and clinical benefit were 6.8 months (95% CI: 0.8-12.7) and 17.1 months (95% CI :12.2-21.9), respectively. Median PFS of patients who received mHTBev was longer than mBev without HT (13 months and 4.1 months, respectively, p = 0.05). The most common severe toxicities were proteinuria (11.4%) and hypertension (8.5%). No additional toxicity was observed with HTBev.Conclusion: Maintenance bevacizumab with or without anti-hormonal therapy in patients with hormone receptor positive breast cancer is tolerable and associated with long-term clinical outcome; these results encourage the strategy of prolonging bevacizumab until progression in combination with anti-hormonal agents

First-line erlotinib and fixed dose-rate gemcitabine for advanced pancreatic cancer

AIM: To investigate activity, toxicity, and prognostic factors for survival of erlotinib and fixed dose-rate gemcitabine (FDR-Gem) in advanced pancreatic cancer. METHODS: We designed a single-arm prospective, multicentre, open-label phase II study to evaluate the combination of erlotinib (100 mg/d, orally) and weekly FDR-Gem (1000 mg/m2, infused at 10 mg/m2per minute) in a population of previously untreated patients with locally advanced, inoperable, or metastatic pancreatic cancer. Primary endpoint was the rate of progression-free survival at 6 mo (PFS-6); secondary endpoints were overall response rate (ORR), response duration, tolerability, overall survival (OS), and clinical benefit. Treatment was not considered to be of further interest if the PFS-6 was < 20% (p0 = 20%), while a PFS-6 > 40% would be of considerable interest (p1 = 40%); with a 5% rejection error (α = 5%) and a power of 80%, 35 fully evaluable patients with metastatic disease were required to be enrolled in order to complete the study. Analysis of prognostic factors for survival was also carried out. RESULTS: From May 2007 to September 2009, 46 patients were enrolled (male/female: 25/21; median age: 64 years; median baseline carbohydrate antigen 19-9 (CA 19-9): 897 U/mL; locally advanced/metastatic disease: 5/41). PFS-6 and median PFS were 30.4% and 14 wk (95%CI: 10-19), respectively; 1-year and median OS were 20.2% and 26 wk (95%CI: 8-43). Five patients achieved an objective response (ORR: 10.9%, 95%CI: 1.9-19.9); disease control rate was 56.5% (95%CI: 42.2-70.8); clinical benefit rate was 43.5% (95%CI: 29.1-57.8). CA 19-9 serum levels were decreased by > 25% as compared to baseline in 14/23 evaluable patients (63.6%). Treatment was well-tolerated, with skin rash being the most powerful predictor of both longer PFS (P < 0.0001) and OS (P = 0.01) at multivariate analysis (median OS for patients with or without rash: 42 wk vs 15 wk, respectively, Log-rank P = 0.03). Additional predictors of better outcome were: CA 19-9 reduction, female sex (for PFS), and good performance status (for OS). CONCLUSION: Primary study endpoint was not met. However, skin rash strongly predicted erlotinib efficacy, suggesting that a pharmacodynamic-based strategy for patient selection deserves further investigation

Prospective study on nanoparticle albumin-bound paclitaxel in advanced breast cancer. Clinical results and biological observations in taxane-pretreated patients

Background: There is a deep need to improve the care of metastatic breast cancer (MBC) patients, since even today it remains an incurable disease. Taxanes are considered the most effective cytotoxic drugs for the treatment of MBC, both in monotherapy and in combined schedules, but the need for synthetic solvents contributes to the severe toxicities and may have a negative impact on the efficacy. Nanoparticle albumin-bound paclitaxel (Nab-paclitaxel) is a colloidal suspension of paclitaxel and human serum albumin initially developed to avoid the toxicities associated with conventional taxanes. Patients and methods: The aim of this prospective, single-center open-label, noncomparative study was to evaluate the efficacy and safety of nab-paclitaxel in MBC patients pretreated with taxanes. The patients were treated with nab-paclitaxel as a single agent, 260 mg/m2 on day 1 of each 3-week cycle or 125 mg/m2 weekly. The primary endpoint was the overall response rate (ORR). Secondary objectives were duration of response, clinical benefit rate, progression-free survival (PFS), overall survival, and safety. Results: A total of 42 patients (median age 48 years, median Eastern Cooperative Oncology Group performance status 0, triple-negative MBC 19%, all pretreated with a taxane-based therapy, mainly in advanced disease) were enrolled in the study. The ORR was 23.8%, including one complete response (2.4%) and nine partial responses (21.4%); the disease control rate was 50%. The median duration of response was 7.2 months. After a median follow-up of 9 months, the median PFS was 4.6 months. ORR and PFS were similar irrespective of the previous chemotherapy lines, metastatic sites, and biomolecular expression. Nab-paclitaxel was well tolerated, and the most frequent treatment-related toxicities were mild to moderate (grades 1–2). Conclusion: This real-life study shows that nab-paclitaxel has a significant antitumor activity and a manageable safety profile in patients pretreated with taxanes and experiencing a treatment failure after at least one line of chemotherapy

COX-2 targeting in cancer: a new beginning?

Cyclo-oxygenase-2 (COX-2), the inducible enzyme catalyzing the rate-limiting step in the conversion of arachidonic acid into eicosanoids, is overexpressed in a wide variety of malignancies and associates with poor prognostic features [1]. Consequently, selective COX-2 inhibitors have been explored as therapeutic or chemopreventive agents in different settings; however, initial enthusiasm was tempered by reports of substantial gastrointestinal toxicity as well as of increased cardiovascular risk, mostly coming from postmarketing use as anti-inflammatory drugs and Cancer Research Campaign (UK) chemoprevention trials and eventually resulting in the withdrawal of rofecoxib from the market [2]

Photoanodes for Aqueous Solar Cells: Exploring Additives and Formulations Starting from a Commercial TiO2 Paste

Whereas the commercialization of dye‐sensitized solar cells (DSSCs) is finally proceeding taking advantage of their low cost and tunable optical features, such as colour and transparency for both indoor and building‐integrated applications, the corresponding aqueous counterpart is still at its infancy. As the TiO2 electrode is a fundamental component for hybrid solar cells, this work investigates the effect of different molecular (α‐terpineol, propylene carbonate) and polymeric (polyethylene oxide, polyethylene glycol, carboxymethyl cellulose and xanthan gum) additives that can be introduced into a commercial TiO2 paste for for screen‐printing (or doctor blade). Among all, the addition of polyethylene glycol leads to the best cell performances, with markedly increased short‐circuit current density (+18 %) and power conversion efficiency (+48 %) with respect to the pristine (commercial) counterpart. When further explored at different concentration levels, electrodes fabricated from polyethylene glycol‐based pastes show different morphologies, thicknesses and performances, which are investigated through (photo)electrochemical, structural, physical‐chemical and microscopic techniques