A phase I clinical and pharmacological study evaluating vinflunine in combination with doxorubicin as first line treatment in metastatic breast cancer.

Vinfunine (VFL) is a novel bifluorinated tubulin-targeted agent of the vinca alkaloids class active in advanced stage breast cancer. We conducted a phase I study combining VFL with doxorubicin (DXR) to define the recommended dose (RD), safety, pharmacokinetic (PK) interaction and efficacy. Two schedules (day 1 every 3 weeks; days 1 and 8 every 3 weeks) were investigated as first line chemotherapy in metastatic breast cancer patients. Thirty-two patients received a total of 162 cycles of the VFL-DXR combination (median 6). The RDs were VFL 250 mg/m(2)/DXR 40 mg/m(2) every 3 weeks for schedule 1 and VFL 120 mg/m(2)/DXR 25 mg/m(2) days 1 and 8 every 3 weeks for schedule 2. The main dose-limiting toxicity was neutropenia. The most frequent non-hematological adverse events were nausea, fatigue, constipation, vomiting, anorexia, stomatitis and dyspnea. Objective response rate was reached in 47.1% of the patients. No PK interaction was observed. VFL-DXR combination is feasible with manageable toxicity. The antitumor activity was promising and supports further evaluation.

Intra-arterial hepatic fotemustine for the treatment of liver metastases from uveal melanoma: experience in 101 patients.

BACKGROUND: Exclusive liver metastases occur in up to 40% of patients with uveal melanoma associated with a median survival of 2-7 months. Single agent response rates with commonly available chemotherapy are below 10%. We have investigated the use of fotemustine via direct intra-arterial hepatic (i.a.h.) administration in patients with uveal melanoma metastases. PATIENTS AND METHODS: A total of 101 patients from seven centers were treated with i.a.h. fotemustine, administered intra-arterially weekly for a 4-week induction period, and then as a maintenance treatment every 3 weeks until disease progression, unacceptable toxicity or patient refusal. RESULTS: A median of eight fotemustine infusions per patient were delivered (range 1-26). Catheter related complications occurred in 23% of patients; however, this required treatment discontinuation in only 10% of the patients. The overall response rate was 36% with a median overall survival of 15 months and a 2-year survival rate of 29%. LDH, time between diagnosis and treatment start and gender were significant predictors of survival. CONCLUSIONS: Locoregional treatment with fotemustine is well tolerated and seems to improve outcome of this poor prognosis patient population. Median survival rates are among the longest reported and one-third of the patients are still alive at 2 years.

High-dose sequential chemotherapy (ICE) under circulating progenitor cells (CPC) protection in patients with small cell lung carcinoma (SCLC). Preliminary report on a multicentric study

Starting in February 1994, 20 patients (pt) with a median age of 50 years(range 41-63) from 7 European centers have been included. Completedata were obtained in 16 patients so far. CPC were mobilized with chemo(Epirubicine 75 mg/m2 /d, 01 + 02) followed by G-CSF 5 p.gfkg/d for14 days. HD chemo consisted in 3 sequential courses of ICE regimen(UOs. 10 g/m2 , Carbo. 1200 mg/m2 and Etop. 1200 mg/m2 ) underCPC protection and G-CSF 5 p.g/kg/d. Out of the 16 pt, 12 completedfull program (3 cycles). One pt died of septic shock before receivingany ICE course. One pt died during the first ICE of renal insufficiency.Two pt had only 2 courses because of toxicity. Among the 16 pt, responserate (RR) was: 7 CR, 6 PR, 1 PO; 3 pt are not evaluable dueto early withdrawal (overall RR: 13/16 = 81 %). Thirty-nine cycles ofHD chemo were given with a median hematological recovery of 9 days(range 7-12) until neutro. counts> 1.0 x 109 /1 and 9 days (range 717)until thrombo. > 20 x 109 /1. No cumulative, hematological toxicitywas seen. Accrual of patients is still ongoing and updated results will bepresented.

Nd and Pb isotope signatures of the clay-size fraction of sediment core MD99-2227

Nd and Pb isotopes were measured on the fine fraction of one sediment core drilled off southern Greenland. This work aims to reconstruct the evolution of deep circulation patterns in the North Atlantic during the Holocene on the basis of sediment supply variations. For the last 12 kyr, three sources have contributed to the sediment mixture: the North American Shield, the Pan-African and Variscan crusts, and the Mid-Atlantic Ridge. Clay isotope signatures indicate two mixtures of sediment sources. The first mixture (12.2-6.5 ka) is composed of material derived from the North American shield and from a "young" crustal source. From 6.5 ka onward the mixture is characterized by a young crustal component and by a volcanic component characteristic of the Mid-Atlantic Ridge. Since the significant decrease in proximal deglacial supplies, the evolution of the relative contributions of the sediment sources suggests major changes in the relative contributions of the deep water masses carried by the Western Boundary Undercurrent over the past 8.4 kyr. The progressive intensification of the Western Boundary Undercurrent was initially associated mainly with the transport of the Northeast Atlantic Deep Water mass until 6.5 ka and with the Denmark Strait Overflow Water thereafter. The establishment of the modern circulation at 3 ka suggests a reduced influence of the Denmark Strait Overflow Water, synchronous with the full appearance of the Labrador Seawater mass. Our isotopic data set emphasizes several changes in the relative contribution of the two major components of North Atlantic Deep Water throughout the Holocene.

"Relaxar é aprender sobre nós próprios": relaxamento e ioga para crianças na educação pré-escolar

O bem-estar emocional na educação pré-escolar é um processo central, mas também uma componente de qualidade e um propósito educativo (Bertram & Pascal, 2009; Laevers, 2005; Mashford-Scott, Church, & Tayler, 2012). Reconhece-se que um forte sentimento de bem-estar permite que as crianças interajam com confiança no ambiente e aproveitem as oportunidades educativas - aspeto encapsulado no conceito de implicação (Laevers, 1997, 2000, 2005). Os conceitos de bem-estar e implicação são relevantes para a investigação, mas também para uma prática preocupada com a perspetiva da criança, expressa de diferentes formas e através de diferentes linguagens. O relaxamento para crianças é perspetivado como promovendo bem-estar, diminuindo ansiedade e stress (Guillaud, 2004; Silva, 1998) e criando atividades indutoras de sensibilidade e interação (Humblet & Guzman, 2013). A promoção de auto-conhecimento e de cognição social são pontos de contacto entre as sessões de relaxamento e a Educação Experiencial. A comunicação pretende apresentar dados de um estudo realizado no âmbito do Mestrado em Educação Pré-Escolar e Ensino do 1.º CEB, em contexto de Prática de Ensino Supervisionada. A rotina do contexto de estágio incluía um momento de relaxamento, de 20 minutos após o almoço, organizado pela orientadora cooperante há vários anos. As 20 crianças do grupo participaram em diferentes tipos de sessões de relaxamento, tendo sido registados níveis de implicação e de bem-estar usando as escalas de observação desenvolvidas para o contexto português por Portugal e Laevers (2010). As diferentes sessões de relaxamento foram: ioga, meditação guiada com música e massagens. A comparação entre sessões baseou-se nas médias de implicação e bem-estar por sessão e nos indicadores mais referidos pelos observadores. Foram, ainda, realizadas entrevistas individuais às crianças e à cooperante sobre as sessões, analisadas através de uma análise de conteúdo temática. Procurou-se, assim, responder à necessidade de conhecer a forma como as crianças experienciam o bem-estar emocional (Mashford-Scott et al., 2012). Todas as sessões revelaram qualidade nos resultados das duas escalas embora os diferentes formatos tenham resultado em ênfases distintas nos indicadores (persistência e precisão no ioga, vitalidade e relaxamento nas massagens, alegria e ligação com o próprio na música). As crianças identificam o relaxamento como parte do seu dia, revelam preferências específicas e individuais por partes das sessões, embora descrevam mais o que fazem do que o sentem.