Clinical relevance of soluble c-erbB-2 for patients with metastatic breast cancer predicting the response to second-line hormone or chemotherapy

Concentrations of soluble c-erbB-2 were determined in the sera of 64 patients with distant metastasis from advanced breast cancer receiving second-line hormone or chemotherapy in comparison to 35 breast cancer patients without detectable recurrent disease and 17 healthy blood donors. The sera of non-metastatic breast cancer patients contained s-erbB-2 concentrations similar to those of healthy blood donors. Patients with distant metastasis from advanced breast cancer had significantly higher values of s-erbB-2 in comparison to patients with non-disseminated disease (mean: 59.6 vs. 11.6 U/ml; p = 0.022). A significant correlation was observed between s-erbB-2 serum levels and serum LDH concentrations (p < 0.001), levels of alkaline phosphatase (p < 0.001), and the presence of hepatic metastasis (p = 0.001). Time to tumor progression was significantly shorter in patients with s-erbB-2 levels above 40 U/ml (mean: 23.4 vs. 56.7 months; p = 0.002). Furthermore, breast cancer patients with hepatic metastasis and those with elevated s-erbB-2 serum levels above 40 U/ml had limited response to hormone or chemotherapy. Non-responders had significantly higher s-erbB-2 levels (mean: 270.3, range: 42-500 U/ml;) compared with the responder group (mean: 23.1, range: 0-149 U/ml; p < 0.001). Logistic regression analysis indicated that elevated s-erbB-2 serum levels above 40 U/ml independently predicted an unfavorable response to second-line hormone or chemotherapy in patients with advanced metastatic breast cancer. Copyright (C) 2002 S. KargerAG, Basel

Characterisation, expression and ontogeny of interleukin-6 and its receptors in zebrafish (Danio rerio)

10 páginas, 8 figuras, 2 tablasInterleukin-6 (IL-6) is one of the most pleiotropic cytokines due to its importance in both innate and adaptive immune responses and other physiological processes. In this study, we identified the zebrafish (Danio rerio) IL-6 homologue by investigating the synteny between the human (Homo sapiens), the fugu (Takifugu rubripes) and the zebrafish genome. Although zebrafish IL-6 showed a low sequence homology with other IL-6 sequences in other species, it presented a high structural similarity to human IL-6. We also analysed IL-6 expression in several different tissues, along with analysis of the expression of the genes that form the IL-6 receptor complex, IL-6R and gp130. After treatment with bacterial or viral stimuli, zebrafish IL-6 expression was modulated in a manner similar to that of other proinflammatory molecules, such as IL-1β and TNF-α. The expression of IL-6, IL-6R and gp130 was also studied during the ontogeny of zebrafish larvae using quantitative PCR and in situ hybridisation. Our results indicated that the transcripts were detected very early, increased during the first week of life and were predominantly expressed in the head, epidermis and neuromasts of the anterior and posterior lateral line system, suggesting their involvement in the normal development of these tissues.We want to thank the funding from the project CSD2007-00002 “Aquagenomics” of the program Consolider-Ingenio 2010 from the Spanish Ministerio de Ciencia e Innovación. M. Varela gratefully acknowledges the JAE Program, co financed by CSIC and European Social Funds, for a predoctoral grant.Peer reviewe

A Bayesian re-assessment of two Phase II trials of gemcitabine in metastatic nasopharyngeal cancer

The Simon two-stage minimax design is a popular statistical design used in Phase II clinical trials. The analysis of the data arising from the design typically involves the use of frequentist statistics. This paper presents an alternative, Bayesian, approach to the design and analysis of Phase II clinical trials. In particular, we consider how a Bayesian approach could have affected the design, analysis and interpretation of two parallel Phase II trials of the National Cancer Centre Singapore, on the activity of gemcitabine in chemotherapy-naïve and in previously treated patients with metastatic nasopharyngeal carcinoma. We begin by explaining the Bayesian methodology and contrasting it with the frequentist approach. We then carry out a Bayesian analysis of the trial results. The conclusions drawn using the Bayesian approach were in general agreement with those obtained from the frequentist analysis. However they had the advantage of allowing for different and potentially more useful interpretations to be made regarding the trial results, as well as for the incorporation of external sources of information. In particular, using a Bayesian trial design, we were able to take into account the results of the parallel trial results when deciding whether to continue each trial beyond the interim stage

A phase II trial of a biweekly combination of paclitaxel and gemcitabine in metastatic breast cancer

BACKGROUND: Many emerging new drugs have recently been trialled for treatment of early and advanced breast cancer. Among these new agents paclitaxel and gemcitabine play a crucial role, mostly in patients with relapsed and metastatic disease after failure of chemotherapy with antracyclines. METHODS: A phase II study was started in order to evaluate the activity and toxicity of a combination of paclitaxel and gemcitabine in a biweekly schedule on metastatic breast cancer patients previously treated with antracyclines. RESULTS: Twenty-five patients received paclitaxel (150 mg/mq) by 3-hours infusion, followed by gemcitabine (2000 mg/mq) given as a 60 min i.v. infusion (day 1–14) for a maximum of eight cycles. In all patients treatment was evaluated for toxicity and efficacy; four patients (16%) achieved a complete response, 12 (48%) a partial response giving an overall objective response rate of 64%. Stable disease was documented in 5 patients (20%) and progressive disease occurred in 4 patients (16%). CONCLUSION: The schedule of treatment was safe and tolerable from a haematological and non-haematological point of view. These data confirm that the combination of gemcitabine and paclitaxel on a biweekly basis is an effective and well-tolerated regimen in breast cancer patients with prior therapeutic exposure to antracyclines

First-line therapy with gemcitabine and paclitaxel in locally, recurrent or metastatic breast cancer: A phase II study

BACKGROUND: This phase II study evaluated the efficacy and safety of gemcitabine (G) plus paclitaxel (T) as first-line therapy in recurrent or metastatic breast cancer. METHODS: Patients with locally, recurrent or metastatic breast cancer and no prior chemotherapy for metastatic disease received G 1200 mg/m(2 )on days 1 and 8, and T 175 mg/m(2 )on day 1 (before G) every 21 days for a maximum of 10 cycles. RESULTS: Forty patients, 39 metastatic breast cancer and 1 locally-advanced disease, were enrolled. Their median age was 61.5 years, and 85% had a World Health Organization performance status (PS) of 0 or 1. Poor prognostic factors at baseline included visceral involvement (87.5%) and ≥2 metastatic sites (70%). Also, 27 (67.5%) patients had prior adjuvant chemotherapy, 25 of which had prior anthracyclines. A total of 220 cycles (median 6; range, 1–10) were administered. Of the 40 enrolled patients, 2 had complete response and 12 partial response, for an overall response rate of 35.0% for intent-to-treat population. Among 35 patients evaluable for efficacy the response rate was 40%. Additional 14 patients had stable disease, and 7 had progressive disease. The median duration of response was 12 months; median time to progression, 7.2 months; median survival, 25.7 months. Common grade 3/4 toxicities were neutropenia in 17 (42.5%) patients each, grade 3 leukopenia in 19 (47.5%), and grade 3 alopecia in 30 (75.0%) patients; 1 (2.5%) patient had grade 4 thrombocytopenia. CONCLUSION: GT exhibited encouraging activity and tolerable toxicity as first-line therapy in metastatic breast cancer. Phase III trials for further evaluation are ongoing

20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years

The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment

Die Vereinbarkeitsfrage für Männer: Welche Auswirkungen haben Elternzeiten und Teilzeitarbeit auf die Stundenlöhne von Vätern?

Studien zeigen, dass sich viele Väter in Deutschland wünschen, mehr Zeit mit ihren Kindern zu verbringen, dies aufgrund von langen Arbeitszeiten jedoch oft nicht umsetzen können. Elternzeit und Teilzeitarbeit könnten Optionen sein, die Vätern eine bessere Vereinbarkeit von Familie und Beruf ermöglichen. Arbeitsmarkttheorien legen jedoch nahe, dass die Inanspruchnahme solcher Maßnahmen mit Lohneinbußen verbunden ist. Dementsprechend entscheiden sich derzeit viele Väter gegen diese Möglichkeiten zur Vereinbarkeit von Familie und Beruf, da sie finanzielle Einbußen und Karrierenachteile befürchten. Um zu überprüfen, inwieweit diese Erwartungen empirisch fundiert sind, untersucht diese Arbeit daher den Einfluss von Elternzeit und Teilzeitarbeit auf die Stundenlöhne von Vätern. Fixed Effects-Analysen auf Basis des Sozio-oekonomischen Panels (SOEP) 1991-2013 und Familien in Deutschland (FiD) 2010-2013 zeigen, dass Teilzeitarbeit mit Lohneinbußen verbunden ist. Eine Elternzeit wirkt sich hingegen nicht auf die Löhne von Vätern aus - unabhängig davon, ob Väter nur die beiden für sie reservierten Partnermonate oder eine längere Elternzeit in Anspruch nehmen. Die Ergebnisse deuten somit darauf hin, dass die gesetzliche Elternzeit Vätern einen Rahmen bietet, in dem sie sich stärker in ihren Familien engagieren können, ohne berufliche Nachteile zu erfahren.As previous research shows, many German fathers would like to spend more time with their children, but long working hours often restrict their opportunities to do so. Parental leave and part-time work could help fathers to reconcile work and family. Yet, labor market theories predict that using such family-friendly policies may lead to wage penalties. Hence, many fathers decide against using such policies because they fear that parental leave or part-time work will lead to financial penalties and career disadvantages. This article evaluates this concern by empirically examining the effect of parental leave and part-time work on fathers’ hourly wages. Using data from the German Socio-Economic Panel (SOEP) 1991-2013 and Families in Germany (FiD) 2010-2013, results from fixed-effects regression analyses show that part-time work is associated with wage penalties, but parental leave is not - irrespective of whether fathers only took the two months fathers’ quota or longer parental leaves. The results hence indicate that the German parental leave legislation enables fathers to spend more time with their children while protecting them from wage penalties at work