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In the breeding areas a significant fraction of the tritium produced is extracted out from the Breeding Zone by the He gas purging the breeding ceramic in the helium cooled pebble bed (HCPB) blanket concept or transported in solution by the flowing liquid metal alloy in the helium cooled lead lithium (HCLL) blanket concept and then extracted outside the blanket box. Tritium produced inside the breeder can enter the metal structures and can be lost by permeation to the environment. It should therefore be kept under close control throughout the fusion reactor lifetime. In this study the problem of tritium transport in HCPB DEMO blanket has been studied and analysed by means of the computational code FUS-TPC, which has been originally developed to study the tritium transport in HCLL blanket and it has the main goal to provide the total tritium losses into the environment and the tritium inventories inside several HCPB blanket locations (e.g. purge gas and main coolant loops). © 2013 Elsevier B.V.

The 1st International workshop on Environmental, Safety and Economic Aspects of Fusion Power (ESEFP) was held on 13 September 2015 at Jeju Island, South Korea. The workshop was initiated by the International Energy Agency Implementing Agreement on a Co-operative Program on ESEFP. The workshop was well attended with about forty participants representing twelve institutions in ten countries. The presentations covered safety issues and environmental impacts, availability improvement and risk control and socio-economic aspects of fusion power. Safety and licensing gaps between DEMO and ITER were discussed in depth with the consensus output presented as a plenary presentation at the 12th International Symposium on Fusion Nuclear Technology (ISFNT-12). The next workshop is planned to be held in conjunction with the ISFNT-13 in 2017.

Angiogenesis inhibitors have shown antitumor efficacy when combined with chemotherapy. It has been proposed that this potentiation is related to better drug delivery to the tumor due to improved vessel functionality. This work combined classical pharmacokinetics and imaging analysis to study the delivery and distribution of paclitaxel after bevacizumab in ovarian cancer. The study was conducted on ovarian cancer models (A2780-1A9 and IGROV-1) xenografted orthotopically under the bursa of the nude mouse ovary. Mice bearing tumors in the ovary, treated with bevacizumab (150μg/mouse) and 24 hours later with paclitaxel (60mg/kg), were sacrificed and tumor excised for analysis, or monitored for anti-tumor activity. Paclitaxel spatial distribution after bevacizumab was analyzed by MALDI-Mass Spectrometry Imaging (MALDI-MSI) on frozen tumor slices, and compared with adjacent histochemical images stained for CD31 (vessel analysis) and Ki-67 (proliferation/necrosis); total paclitaxel in tumor homogenates, liver and plasma was evaluated by high-performance liquid chromatography (HPLC). Tumor growth of A2780-1A9 and IGROV-1, carrying the firefly luciferase gene luc2, was monitored by Bioluminescence imaging (BLI) and survival recorded. Bevacizumab decreased tumor vessel number/size compared to vehicle treated mice, but potentiated the antitumor activity of paclitaxel in both models. MALDI-MSI showed that after bevacizumab, paclitaxel was more homogenously distributed and mainly in actively proliferating areas of the tumor where vessels were uniformly diffused, despite paclitaxel concentration did not increase after antiangiogenic drug. No changes in paclitaxel systemic exposure was found in normal tissue. These findings suggest that a more uniform distribution of paclitaxel in the tumor of the mouse ovary is responsible for the better antitumor activity of the combination. A.D. and I.F.N. are the recipients of a fellowship from the Italian Foundation for Cancer Research (FIRC). Citation Format: Marta Cesca, Lavinia Morosi, Alexander Berndt, Ilaria Fuso Nerini, Alessandra Decio, Massimo Zucchetti, Raffaella Giavazzi. Bevacizumab-improved distribution of paclitaxel in ovarian cancer xenografts potentiates antitumor efficacy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3377.

The fusion technological consequences of the radioactive decay behaviour of SiC-based structural material were analysed based on a complete chemical analysis of an industrial SiC f /SiC composite. Radioactivation simulation was performed with the FISPACT-2 code and EAF-2 cross-section library, taking n-spectra from the SEAFP reactor study for first wall and blanket. The decay of radioactivity in SiC f /SiC after shut down and derived radiological quantities are presented and compared with those of SEAFP structural materials. The effective dose equivalent (EDE) to the population from accidental release of activated material was computed with the GENII code. SiC f /SiC performs favourably. Contact dose rates and γ-dose rates inside the plasma chamber are given. Assuming an upper limit of 10 4 Gy h −1 for robotized maintenance, SiC f /SiC renders the first wall a zone where immediate repair would be possible. For this short-term activation limit, an elemental “critical list” is presented. Long-term decay heat generation and contact dose rates show which material fulfils waste limits. Although A1-26 is generated in the first wall, SiC f SiC is a safely disposable material, owing to other characteristics such as inertness against corrosion.

A retrospective pharmacokinetic analysis was done of methotrexate serum levels after high-dose treatment (HD-MTX, four cycles at two-week intervals of 5 g/sq.1m. over 24 h i.v.) in children with non-B acute lymphoblastic leukemia (ALL) with the specific aim of seeking differences in patients of different ages, including infants under one year. A total of 122 children (seven infants aged 3 months-1 year, 26 children aged 1-3 years, 68 children aged 3-10 years and 21 adolescents aged 10-15 years) with normal liver and renal function, receiving consolidation therapy at the Pediatric Clinic of Monza between May 1988 and April 1992, were enrolled in this study. MTX was given as an intravenous infusion in 24 h and serum concentrations were measured up to at least 72 h after the start of infusion by an enzyme immunoassay (TDX Abbot, Dallas, TX) in order to modulate folinic acid rescue. Pharmacokinetic analysis of MTX levels according to a two-compartment open model indicated that, compared to all children up to 10 years old, in adolescents older than 10 years the drug reached higher concentrations in serum and was cleared at a lower rate. Steady-state levels and AUC were from 60% higher to more than double and the total clearance of the compound, expressed either per square meter surface area or per kg body weight, in each cycle was significantly lower in adolescents > 10 years of age, sometimes being only one-third of the clearance in infants (0.2 vs. 0.6 1/h/kg and 6.6 vs. 10.7 1/h/sq.m). The relationship between each age and systemic clearance was highly significant as measured by regression analysis. Methotrexate systemic clearance progressively decreased as a function of age. Subsequent treatments did not induce changes in MTX pharmacokinetics. These data suggest that the better tolerance of HD-MTX in children may have a pharmacokinetic basis. The faster elimination of MTX in infants, who usually show the worst prognosis, suggests that full doses could be safely used in order to maximize the antileukemic effect without a high risk of toxicity.

Management aspects of fusion waste are presented. Conditioning and packaging of tritiated waste must cope with the high mobility of tritium. The first required treatment is immobilization of the waste in solid matrices. Additional barriers against tritium migration are provided by encapsulating layers. Packaging is afforded by single or double-walled structures. Low activation materials (LAMs) are being developed to simplify the management of fusion activated waste. Interim storage of this waste is envisaged at the plant site, then various options are possible, depending on the residual radioactivity levels, i.e. declassification to non-active-waste, recycling, disposal.

A simple, reproducible and specific urine assay for the novel epipodophyllotoxin derivative dimethylaminoetoposide (NK611, I) its picro form (III), the N-demethyl metabolite (II) and its picro form (IV) is reported. The method involves the addition of Pr-NK611 as internal standard, chloroform extraction and HPLC separation on a Nova-Pak C18 column with a mobile phase of acetonitrile-0.05 M KH2PO4 (pH 6.4) (23:77, v/v). UV detection was used with absorbance monitored at 205 nm and the limit of quantification was 100 ng/ml. The intra- and inter-day precisions were within the ranges 1.1-3.4% and 1.9-2.4% for all analytes and the accuracy was 101-107%. The extraction recovery was more than 88% for I, II and IV and more than 83% for III. The assay is applicable to the urinary monitoring of I-IV in clinical pharmacokinetic investigations.

E-3810 is a novel small molecule that inhibits VEGF receptor-1, -2, and -3 and fibroblast growth factor receptor-1 tyrosine kinases at nmol/L concentrations currently in phase clinical II. In preclinical studies, it had a broad spectrum of antitumor activity when used as monotherapy in a variety of human xenografts. We here investigated the activity of E-3810 combined with different cytotoxic agents in a MDA-MB-231 triple-negative breast cancer xenograft model. The molecule could be safely administered with 5-fluorouracil, cisplatin, and paclitaxel. The E-3810–paclitaxel combination showed a striking activity with complete, lasting tumor regressions; the antitumor activity of the combination was also confirmed in another triple-negative breast xenograft, MX-1. The activity was superior to that of the combinations paclitaxel+brivanib and paclitaxel+sunitinib. Pharmacokinetics studies suggest that the extra antitumor activity of the combination is not due to higher paclitaxel tumor levels, which in fact were lower in mice pretreated with all three kinase inhibitors, and the paclitaxel plasma levels excluded reduced drug availability. Pharmacodynamic studies showed that E-3810, brivanib, and sunitinib given as single agents or in combination with paclitaxel reduced the number of vessels, but did not modify vessel maturation. Reduced tumor collagen IV and increased plasma collagen IV, associated with increased matrix metalloproteinases (MMP), particularly host MMP-9, indicate a proteolytic remodeling of the extracellular matrix caused by E-3810 that in conjunction with the cytotoxic effect of paclitaxel on the tumor cells (caspase-3/7 activity) may contribute to the striking activity of their combination. These data support the therapeutic potential of combining E-3810 with conventional chemotherapy. Mol Cancer Ther; 12(2); 131–40. ©2012 AACR.

This chapter outlines the attractive environmental features of nuclear fusion, presents an integral scheme to manage fusion activated materials during operation and after decommissioning, compares the volume of fusion and fission waste, covers the recycling, clearance, and disposal concepts and their official radiological limits, and concludes with a section summarizing the newly developed strategy for fusion power plants

Hydrogen dissolves in and permeates through most materials, thus it is important to understand the permeation, diffusion and dissolution phenomena of atomic hydrogen in materials in which hydrogen and its isotopes are present. In this work the problem of tritium transport from lead–lithium breeder through different heat transfer surfaces to the environment has been studied and analyzed by means of a computational code. The code (FUS-TPC) is a new fusion-devoted version of the fast-fission one called Sodium-Cooled Fast Reactor Tritium Permeation Code (SFR-TPC). The main features of the model inside the code are described. A simulation, using the code, was performed by adopting the configuration of the European configuration of the Helium Cooled Lead Lithium (HCLL) blanket for DEMO.

This paper aims to introduce utilities and dangers using ICT in teaching cinema. As digital convergence offered new opportunities in many fields, it stressed the needs for to make some reflections and thus consequently to acquire the appropriate skills. We will discuss how cinema and ICT are re-lated in educational contexts especially when cinema is not the specific topic. Cinema and audiovisual media are always more necessarily invited guests into lessons of various subjects and courses in order to convey messages to the students through images. As required by the dynamics of the contemporary. Then the essay introduces a practical case in which movie has contributed to develop a theme and has helped students to better understand far phe-nomena from them.

Ceramic matrix composites based on SiC with continuous fibres (SiC f /SiC) are considered promising structural materials for future fusion devices. It was still to clarify, whether impurities in industrial SiC f /SiC could jeopardise radiological advantages. Experimental impurity analyses revealed a two-dimensionally reinforced SiC f /SiC with the matrix produced by CVI as very pure. Chemo-spectrometric methods were combined with radioactivation methods (CPAA, NAA). A quantification of the main constituents Si, C and O was added. Calculations with the FISPACT-2.4 code and EAF-2 library identified elements detrimental for different low-activation criteria. For the neutron exposure, EEF reactor-study first wall and blanket conditions were simulated. The calculated SiC f / SiC included 48 trace elements. Even under conservative assumptions, all low-activation limits of European interest are fulfilled. Exclusively the hands-on recycling limit for the First Wall can intrinsically not be satisfied with SiC. The theoretical goal of a SiC f /SiC depleted of 28 Si (isotopic tailoring) is critically discussed.

The short-term radioactivity of some candidate structural materials for fusion reactors (reference steels and non-ferrous “low activation” materials) has been analyzed in power relevant conditions of inertial and magnetic fusion energy (IFE and MFE) reactors. Materials are assessed with regard to accident safety, using an offsite dose-related criterion. It turns out that the best option for IFE differs from that of MFE. For some materials in IFE conditions, the potential off-site dose can be largest when radioactivity release occurs sometime during reactor operation rather than at the end of its lifetime.

The utilisation of low-activation materials (LAMs) has been recommended in the Report of the CEC Fusion Evaluation Board (“Colombo Report”) as a mean to demonstrate the safety and environmental feasibility of fusion. On this basis, criteria for the choice and the development of LAMs are proposed. They are based on the compliance to short- and long-term radioactivity limits and relate to accidental situations, maintenance and waste management. The relative importance, or ranking, of each criterion is adjusted to the peculiar properties and requirements of each reactor component. Activation levels of typical constituting materials are evaluated for each component and compared with the relevant criteria. Materials composition data for the development of novel LAMs are defined. Low activation reference tables are also presented.

The antileukaemic efficacy of L-asparaginase is related to the ability of the enzyme to induce the complete disappearance from plasma of L-asparagine, an amino acid essential to lymphoblastic leukaemia cells. It is not feasible to monitor L-asparagine plasma levels in patients under L-asparaginase treatment using the usual analytical procedures as the enzyme continues the hydrolysis of L-asparagine after blood sampling and during plasma extraction. A method was therefore developed for the determination of L-asparagine in patients receiving L-asparaginase. Sulphosalicylic acid is added to blood samples to deproteinize and inactivate L-asparaginase rapidly. The samples are then analysed by HPLC using a Novapack C18 column and fluorescence detection. With the same method L-asparagine is determined in blood cells and, by difference, plasma levels are calculated. This method is highly specific and sufficiently simple and sensitive for clinical use.

A simple, rapid and reproducible plasma assay for the determination of the novel epipodophyllotoxin derivative, dimethylaminoetoposide (NK611, I) and its N-demethyl metabolite (II) is reported. The method involves solid-phase extraction using an isolute C18 cartridge and HPLC separation on a reduced-activity C18 column (8 cm long) with a mobile phase of acetonitrile-water-0.1 M phosphoric acid (23:76:1, v/v/v); peaks are detected at 205 nm. The intra- and inter-day precision and accuracy are within 5 and 4% for I and II, respectively. The sensitivity is 20 ng/ml for both I and II. The assay is applicable to clinical pharmacokinetic studies. In one cancer patient who received both an oral and an intravenous dose of 10 mg of I the bioavailability was 82% and the clearance 20.8 ml/min.

This contribution presents an analysis of the question of using waste materials as building materials, addressing the question of their radioactivity. The building industry uses large amounts of waste products from other industries. In recent years, there is a growing tendency to use new construction materials with naturally or technologically enhanced levels of radioactivity (e.g. phosphogypsum, coal fly ash, oil shale ash, some rare minerals, etc.). Increased interest in measuring radionuclides and radon concentration in building materials is due to the health hazards and environmental pollution. Discussion of regulating international norms and of international worldwide studies is carried out, drawing conclusions on the relevance of the problem. An experimental measurement case study in Italy has been carried out and results discussed

Cisplatin is one of the most effective cytotoxic agents in the treatment of solid malignancies, but its use is limited by several side effects. Among them, peripheral neurotoxicity can be dose limiting. A liposomal formulation of cisplatin, Lipoplatin™, was developed to reduce the systemic toxicity of cisplatin but without preventing its efficacy. The aim of this study was to use an animal model to establish, through a multimodal approach, whether chronic treatment with two different schedules of Lipoplatin™, selected within the range of its anticancer effective dose, is less neurotoxic than cisplatin administration. Female Wistar rats were treated intraperitoneally with cisplatin at a dose of 4 mg/kg or with Lipoplatin™ at doses delivering 12 or 24 mg/kg of cisplatin once weekly for 4 weeks. General toxicity was assessed by daily observation, body weight change, hematological and blood chemistry analysis, and histopathology of liver and kidney. The onset of peripheral neurotoxicity was assessed by measuring tail nerve conduction velocity (NCV), morphological and morphometric analysis of dorsal root ganglia (DRG), and morphological analysis of the sciatic nerve. Cisplatin induced a statistically significant reduction in body weight, the development of renal failure, and impairment in NCV with pathological alterations in the DRG and sciatic nerve. By contrast, Lipoplatin™ was markedly less nephrotoxic, and no significant weight gain reduction was observed in animals treated with both doses of the drug. Moreover, the lowest dose induced less severe damage to the peripheral nervous system with a moderate decrease in NCV and mild pathological alterations in DRG and the sciatic nerve. The results suggest that Lipoplatin™ 12 mg/kg is less neurotoxic than cisplatin 4 mg/kg, thus opening up the possibility of using this new formulation in future studies where its anticancer activity and the peripheral neurotoxicity will be assessed in parallel.

In the past, Shallow Land Burial (SLB) was considered one suitable solution for the management of fusion activated waste, the other being Recycling. These concepts have influenced the development of low activation materials for fusion (LAMs), having reduced long-term radioactivity. Present European studies, however, do not consider SLB a viable option and concentrate more on Geological Disposal (GD). A classification of activated materials into High-, Medium-, and Low-Level Waste is proposed, taking into account contact dose rates and decay heat levels, in compliance with the GD and Recycling alternatives. This proposal is also consistent with integral criteria to classify LAMs, based on both the short- and long-term radioactive behavior. Applications of these rating criteria to activated components from various fusion designs are shown.

Author Summary Background. Molecular alterations of the PI3K and Ras pathways often occur in human cancer. In this trial, the pharmacokinetics, toxicity, and activity of two drugs inhibiting these pathways—everolimus and sorafenib—were investigated. Methods. Thirteen patients with progressing solid tumors were treated with everolimus and sorafenib, according to a 3+3 scheme. Patients were selected on the basis of immunohistochemical expression of tumor molecular targets, including phospho-AKT, -p70S6K, and -ERK1/2. Results. The daily recommended dose identified was 2.5 mg of everolimus and 600 mg of sorafenib. Dose-limiting toxicities included grade 3 asthenia and hand-foot skin reaction. No grade 4 adverse events were observed. The most frequent grade 3 toxicities were hypophosphatemia (30.8%), alanine aminotransferase level increase, asthenia, and anorexia (14%). No pharmacokinetic interactions were identified between everolimus and sorafenib. Of 12 evaluable patients, we observed 2 partial responses, with greater than 10% shrinkage in an additional 5 patients. Objective responses were observed in one patient with a thymoma and in one patient with a lung adenocarcinoma. Tumor shrinkage that did not qualify as a partial response was seen in an abdominal leiomyosarcoma and in adenoid cystic carcinomas. Conclusion. The combination of everolimus and sorafenib is safe. The tumor activity observed in different tumor types could be the result of the combined action of these drugs as well as the molecular selection of the treated population. Further research is warranted to better investigate drugs simultaneously blocking the PI3K and the Ras pathways and to refine patient selection.

Purpose: Acetyl-l-carnitine (ALC) plays a relevant role in energy metabolism and stress response because of its function in the complex metabolic system regulating the acetyl-CoA levels that provide a source of acetyl groups for metabolic and acetylation-regulated processes. Because acetylation may influence p53 activity/stability and, therefore, the response to platinum compounds, this study was designed to investigate the effect of ALC in combination with platinum compounds. Experimental Design: The antiproliferative and antitumor activity studies were done in a panel of human tumor cell lines with functional or defective p53. The antimetastatic drug efficacy was investigated in the s.c. growing H460/M tumor subline, which is able to generate lung metastases. Results: ALC enhanced the sensitivity to cisplatin of tumor cells with functional p53. The sensitization by ALC was reflected in an improved in vivo antitumor efficacy of the combination over cisplatin alone in wild-type p53 lung tumors. ALC did not increase the cisplatin efficacy in the p53-mutant SW620 tumor. ALC exhibited a significant antimetastatic activity, and this effect was better exploited in combination with the histone deacetylase inhibitor, ST3595. The in vivo ALC/cisplatin combination caused the activation of p53, associated with protein acetylation and induction of target genes. Conclusions: ALC was effective in enhancing the antitumor potential of platinum compounds in wild-type p53 tumors. ALC, alone and in combination with a histone deacetylase inhibitor, exhibited an outstanding antimetastatic activity. Both effects, likely mediated by protein acetylation, may have implications for platinum-based therapy and combinations with histone deacetylase inhibitors. Clin Cancer Res; 16(15); 3944–53. ©2010 AACR.

Low activation materials are only a partial response to the requirement of a really environmentally sound fusion reactor: another way round to tackle the problem is the reduction of the neutron flux and subsequent material irradiation, possibly by exploring other possible fusion reactions such as the Deuterium-Helium-3 one.

The radioactive behaviour of silicon carbide is compared to that of other structural materials proposed for fusion applications. This analysis takes into account short- and long-term issues like accident safety, maintenance and waste management. Low activation criteria based on the compliance with radioactivity limits are proposed. According to these criteria, steels can hardly be considered as possible low-activation materials. Even the elementally-tailored reduced activation steels can never fulfil completely all criteria. Vanadium alloys and SiC in the form of a new ceramic matrix/ceramic fibre composite (“SiC/SiC”) must be regarded as the most promising low-activation materials, as far as radiological/activation behaviour is concerned. Some of the problems associated with the activation of vanadium alloys are examined. SiC/SiC turns out to be an ideal low-activation material as all criteria are fulfilled. Attention is given to the activation of SiC impurities.

The development of effective chemotherapy for tumors of the central nervous system (CNS) is complicated in that the blood-brain barrier (BBB) hampers the penetration of most drugs into the brain and cerebrospinal fluid (CSF). This review summarizes the main reports on the distribution to CNS tumors and peritumoral normal brain of antitumor agents such as epipodophyllotoxins, cis-diamminedichloroplatinum(II), some nitrosoureas, bleomycin, vinblastine, and other clinically used antitumor agents as well as that of some experimental compounds with specific physicochemical properties. Drug levels were measured at surgical resection or in autopsy samples taken from patients who presented with different primary brain tumors or with brain metastases from extracerebral tumors. The observations made in each study were summarized in some detail, and the main points were then evaluated comparatively so as to highlight common aspects in the pharmacokinetic patterns of antitumor agents in human CNS tumors. Independently of their physicochemical properties, most antitumor agents appear to accumulate to a greater extent and to persist longer in intracerebral tumors than in the normal peritumoral brain. From in vitro cytotoxicity assays, it appears that epipodophyllotoxins, platinum compounds, bleomycin, and nitrosoureas reach potentially active therapeutic concentrations at the tumor target. However, all drugs have difficulty in reaching brain tissue adjacent to the tumor, as the intact BBB hampers their penetration. Plasma and CSF drug concentrations usually give little useful indication of the absolute quantity of drugs in brain tumors. To obtain a clear understanding of the CNS distribution of antitumor agents, one must determine whether the compound being measured is actually responsible for the observed activity and must consider the role of metabolites in the effect of the parent drug.

E-3-(4′-Hydroxy-3′-adamantylbiphenyl-4-yl) acrylic acid (ST1926) is a novel oral synthetic adamantyl retinoid derivative, now under early clinical investigation in patients with ovarian cancer. To investigate the pharmacokinetics of this new antitumor agent in human plasma, we developed and validated a high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method based on the addition of ST2222 as internal standard and simple protein precipitation with methanol. The method requires a small volume of sample (100 μL); it is rapid and selective, allowing a good resolution of peaks from the plasma matrix in 9 min. The method offers high recovery (>90%), it is sensitive, precise and accurate with overall precision expressed as CV% less than 8.2%. We set the lower limit of quantitation at 20.0 ng/mL and validated the assay up to the concentration of 1000.0 ng/mL. The present method has been successfully applied to study ST1926 pharmacokinetics in patients with advanced ovarian cancer in a Phase I trial, administering the drug orally for five consecutive days. During analysis of the study samples, it became evident the presence of glucuroconjugates of the parent compound, established by LC-Orbitrap MS. Preliminary results show low and variable drug absorption in patients, with extensive glucuroconjugation influencing the bioavailability of ST1926.

Aim of the study To define the maximum tolerated dose (MTD) and toxicity of trabectedin (T) and cisplatin (C) given on days 1 and 8 every 3weeks to adult patients with advanced solid tumours. Plasma pharmacokinetics at cycle 1 and a preliminary anti-tumour activity assessment in ovarian and non-small cell lung cancer (OC, NSCLC) were secondary objectives. Methods In the dose finding part (DFP) of the study the dose of T given at each administration was escalated by 100μg/m 2 increments from 300μg/m 2 up to the MTD, with a fixed dose of C of 40mg/m 2 . The recommended dose (RD) was assessed in the previously treated and untreated OC and NSCLC patients in the expansion of the RD (ERD) part of the study. T was administered with corticosteroids pre-medication as 3-h infusion and C as 30-min infusion. Results Thirty-nine patients were treated in the DFP and 10 in the ERD. The MTD of T was 700μg/m 2 due to dose-limiting neutropaenia and the RDs in the previously treated/untreated patients were 500 and 600μg/m 2 , respectively. Most common toxicities were nausea/vomiting (67%), asthenia/fatigue (55%) and reversible ASAT/ALAT elevation (51%). Time to recovery from myelosuppression was dose-dependent and treatment could be repeated after ⩾4weeks in the majority of patients at 600μg/m 2 . Confirmed partial responses were observed in 4 of 13 evaluable OC patients and in 1 with uterine leiomyosarcoma. No pharmacokinetic interaction was observed. Conclusion The administration of T and C on days 1 and 8 resulted in prolonged neutropaenia requiring treatment delay. The evaluation of a single every 3week schedule is worthwhile because of the hints of anti-tumour activity observed in OC.

This study addresses an integrated approach to the management procedures for active mate-rials following the changeout of replaceable components and decommissioning of fusion facilities. The attractive environmental features of fusion are put into evidence, and the question of nuclear weapon proliferation relevance of fusion power plants is briefly discussed. Reference is made to previous U.S. and European assessments of the back-end for fusion power plant studies, stressing that most materi-als can be cleared or recycled, and/or disposed of as low-level waste. Just recently, both clearance and recycling concepts and limits have been revised by national and international organizations. These revisions and their consequences have been examined in this paper and the references therein. A new radioactive materials management strategy has been proposed for the clearance, recycling, and disposal approaches

Ignitor is a proposed compact high-magnetic field tokamak aimed at studying plasma burning conditions in Deuterium-Tritium plasmas. Localisation of this experiment in Italy has seen growing attention during the last years. The determination to carry out this project in Italy has driven to taking into account several candidate sites. Recently, due to several technical reasons, it was identified a new site, the Caorso Site, in northern Italy, a nuclear site were a nuclear power reactor was sited. Preliminary Radiological Impact analyses for the siting of Ignitor in Caorso are presented in this paper. Te Ignitor radiological impact turns out to be negligible both during normal operation and in case of accident.

The problem of neutron-induced radioactivity in magnet structural materials for fusion reactors is examined. Two near-term reactor designs (NET-DN and ITER) are considered. Long-term activation of these materials is low enough to permit their recycling after less than 25 years of intermediate decay. Short-term radioactivity, on the other hand, requires the remote handling of these components for relatively long periods after shutdown. To permit a nearly immediate direct handling, activation of magnet structural materials must be reduced. For this purpose, two possible actions are considered: materials selection and improvement of the shielding. All the candidate materials for structural use in magnet components have a comparable activation behaviour. As far as the improvement of the shielding is concerned, the most interesting problem turns out to be the modification of the inboard shield in ITER. With some slight modifications, the goal of the direct handling for magnet materials is eventually reached. Finally, the activation of magnet materials in a next-step machine like DEMO is briefly examined.

Research on the eutectic Pb17Li is part of the blanket studies carried out in Europe for fusion power reactors. The use of this breeder makes easier some safety problems as compared to the case of lithium as a consequence of the lower chemical reactivity of Pb17Li. On the other hand, it increases the radioactivity problems due to the neutron activation of lead and impurities. This paper presents both short-term (accidents) and long-term (waste disposal and recycling) aspects of the Pb17Li activation products. They include the production, mobilization, release and environmental impact. Concerning accidents, a particular attention is given to Po-210 and Hg-203. Questions related to waste management are also revised. The most attractive solution seems that of recycling the spent Pb17Li. This will be possible about 20 y after removal from service. As an alternative to recycling, the breeder disposal as radioactive waste is discussed.

The potential decay heat stored in a fusion reactor after a year of normal operation, is theoretically enough to cause, at least, a partial meltdown of the reactor structure. A narrow sector of ITER fusion reactor has been modelled in conditions similar after a total LOCA (Loss of Coolant Accident). The purpose was to estimate the temperature histories of the various components in a period up to 10 days after the accidental shutdown. It was verified that no melting at the first wall or the blanket is to be expected during the first 10 days after the accident.

Neutron-induced activity in the PCA austenitic stainless steel is examined, when used for first-wall components in a DEMO fusion reactor. Some low-activity definitions, based on different waste management and disposal concepts, are introduced. Activity in the PCA is so high that any recycling of the irradiated material can be excluded. Disposal of PCA radioactive wastes in Shallow-Land Buriable (SLB) is prevented as well. Mo, Nb and some impurity elements have to be removed or limited, in order to reduce the radioactivity of the PCA. Possible low-activity versions of the PCA are introduced (PCA-la); they meet the requirements for SLB and may also be recycled under certain conditions.

The main features of a tritium breeding blanket for a Demonstration Power Reactor involving the eutectic Pb-17Li as liquid breeder and water as coolant are presented. The configuration of the blanket segments and breeder modules as well as their arrangement inside the reactor vacuum vessel are outlined. The main design aspects and the corresponding design limits are reviewed, namely those related to thermomechanics, neutronics, magneto-hydrodynamics, tritium permeation and recovery. First results of safety analyses, in particular those connected with the rupture of a coolant tube in the breeder module are presented and discussed. As a conclusion, the feasibility of the concept looks attractive. A problem which requires further investigation is that of the tritium self-sufficiency. It is shown that a net tritium production near to one can be obtained if beryllium tiles are placed in front of the plasma, provided that they are cooled by heavy water.