European Cancer Research Research Articles

More and better cure for an orphan: priorities for future paediatric cancer research in Europe – Meeting report of the EC-funded science-communication project DIRECT “Overcoming Cancer with Research”

Although cure rates for childhood cancer have improved from below 20% to more than 75% during the last 40 years, childhood cancer is still the number one killer amongst paediatric diseases. European paediatric cancer research also faces new challenges by the increasing number of childhood cancer survivors, some of whom experience significantly altered life-quality due to serious psychosocial and medical long-term side-effects of the intensive cancer treatment. Hence, to achieve even higher quantity and quality of cure for Europe’s children and adolescents with cancer, development of new treatment options is now required, as are intensified epidemiological investigations into health and psycho-social issues of paediatric cancer survivors on the EU-level. Based on presentations and discussions at a recent meeting of leading European paediatric oncologists supported by the EC-funded science-communication project “DIRECT", this article discusses the situation of European paediatric cancer research under the EU-Framework Programmes (FPs). Single, partially interlinking paediatric oncological research projects received EU-funding during the last three FPs. However, given the increased budgets for health research under the FP6 and FP7 together with their goal to improve the European Research Area (ERA), relatively few of the current challenges in European paediatric oncology have been covered so far when compared to the spending for adult cancer. Although still fragmented, current EC-funded projects in paediatric oncology would be amenable to a higher level of integration. In order to achieve a closer approach to “total cure” including all medical, psychological and social aspects, paediatric cancer should become a horizontal priority of European research funding.

3500 EUROCOURSE: towards optimisation of the use of cancer registries for scientific excellence in cancer research in Europe: an FP7 ERA-net project

3500 EUROCOURSE: towards optimisation of the use of cancer registries for scientific excellence in cancer research in Europe: an FP7 ERA-net project

Survival from cancer of the pancreas in England and Wales up to 2001.

Survival from cancer of the pancreas in England and Wales up to 2001.

Trends in the global funding and activity of cancer research

Cancer research has carved an astonishing trajectory giving rise to a multi billion euro global network covering most domains of science and including all manner of research funders from industry to government and philanthropic funders. We have estimated that in 2004/2005 the global spend on cancer research was 14,030 million euros, with the USA, dominated by the NCI (c. 83%) accounting for the largest absolute spend. This is between 2 and 3 times the level of per capita spend compared to EU-15 and Europe, respectively. In Europe, the UK is at comparable levels of spend compared to the USA. Funding for cancer research in Europe is split almost 50:50 between philanthropic and governmental sources. Cancer research productivity in terms of outputs (publications) is slightly greater in Europe compared to the USA with an increasing trend towards more applied (clinical) outputs. Both the USA and Europe have equally strong industry-supported output levels.

Improvement of European Translational Cancer Research. Collaboration between Comprehensive Cancer Centers

Even though the increasing incidence of cancer is mainly a consequence of a population with a longer life span, part of this augmentation is related to the increasing prevalence of patients living with a chronic cancer disease. To fight the problem, improved preventive strategies are mandatory in combination with an innovative health care provision that is driven by research. To overcome the weakness of translational research the OECI is proposing a practical approach as part of a strategy foreseen by the EUROCAN+PLUS feasibility study, which was launched by the EC in order to identify mechanisms for the coordination of cancer research in Europe.

Policy Challenges for Cancer Research: A Call to Arms

Research has delivered remarkable benefits for cancer patients and their families since James Watson and Francis Crick wrote the now immortal line, ‘We wish to propose a structure for the salt of deoxyribonucleic acid’ thus setting the molecular foundations for the modern era of cancer control. The pace of technological innovation from fundamental scientific discoveries to the policy impact of huge population studies has been breathtaking. One has only to contrast a paper on the treatment of solid epithelial cancers written by Henri Tagnon and colleagues in 1966 (Eur J Cancer 2 51–7) with the myriad of chemotherapeutic approaches at the oncologists disposal today. Inevitably, as the tide of research has risen so it has bought the flotsam and jetsam of regulations and policies. Some have been helpful, many pointless and too many actually harmful. Naturally, some of these regulatory and general policies (by this I mean those concerned with funding, structure and organization) have been specifically targeted at cancer research, e.g. US National Cancer Act 1971, whilst others have been a product of the general regulatory environment with indirect consequences for cancer research, e.g. EU Data Protection Directive 1995. Policy issues thus cover a vast terrain criss-crossed by complex interdependencies between scientific areas, countries S&T policies and socio-political constructs. Unfortunately, there has been little attention paid to the consequences of these policy issues from which the research community has, by and large, been passenger rather than driver.Global investment in cancer research is now at unprecedented levels. The recently published report by the European Cancer Research Managers Forum has found some 14 billion euros being annually spent worldwide on cancer research (this figure includes industry but overall probably underestimates spend by at least one billion [2]). With the ageing demographics of developed countries and the catch-up effect in developing countries, the rising burden of cancer is driving research activity in cancer ever upwards. Opportunities for delivering even greater measures for preventing and controlling cancer abound, but the shackles of bureaucracy (stifling regulations and poor research policies) threaten this future more than ever—‘Man is born free and everywhere he is in chains’. Jean-Jacques Rousseau’s quote could equally be applied to spirit of research creativity in today’s environment. So what are the main issues and what is to be done?

700 POSTER Outcome of the Clinical Trials Directive on clinical cancer research in Europe: a 3-years'-follow-up analysis

Sildenafil citrate is indicated for the treatment of erectile dysfunction. An orally disintegrating tablet (ODT) of sildenafil citrate has been developed for the benefit of patients who have difficulty swallowing solid dosage forms.The main goal of this study was to evaluate the bioequivalence of sildenafil ODT with and without water versus marketed sildenafil oral film-coated tablets. A secondary objective was to evaluate the effects of a high-fat meal on the pharmacokinetics of sildenafil ODT.The bioequivalence study of sildenafil ODT given with and without water versus marketed sildenafil citrate film-coated oral tablets was conducted in 36 subjects. In a food-effect study, the effect of a standard high-fat meal on the pharmacokinetics of sildenafil ODT was evaluated in 12 subjects. Both studies were randomized, open-label, crossover, single-dose (50 mg) studies in healthy men aged ≥45 years. Plasma samples were collected for 14 hours postdose, and pharmacokinetics were determined by using noncompartmental analyses.All subjects in both studies were Asian males between the ages of 45 and 69 years. Sildenafil ODT without water was bioequivalent to the marketed sildenafil film-coated oral tablet as the 90% CI for the ratio of geometric means of Cmax, AUC0–∞, and AUC0–last were contained within equivalence limits (80%–125%). When sildenafil ODTs were given with water, the 90% CIs for sildenafil AUC0–∞ and AUC0–last were contained within the range of 80% to 125%; however, the 90% CI for sildenafil Cmax was not (79.76–92.78). This difference in Cmax is unlikely to have any clinically meaningful impact. High-fat meals reduced the rate but not the extent of absorption of sildenafil. Mean Cmax was reduced by 59%, and median Tmax was delayed from 0.625 hour (fasting) to 4 hours (high-fat meal). However, AUC values were comparable between fed and fasted treatments.Sildenafil ODT, given with or without water, provides equivalent systemic exposure compared with marketed sildenafil film-coated oral tablets, thus offering a convenient alternative method of administration. Considering the results of the food-effect study, sildenafil ODT should be taken on an empty stomach. ClinicalTrials.gov identifiers: NCT01254383 (bioequivalence) and NCT01254396 (food effect).

120 INVITED Should the coordination of the European cancer research and care be built on national programmes?

120 INVITED Should the coordination of the European cancer research and care be built on national programmes?

EACR-19: The best of European cancer research

The 19 th biennial meeting of the European Association of Cancer Research, EACR-19, was held in Budapest, the splendid capital of Hungary, in June 2006. It proved an exciting forum for researchers engaged in basic, translational and clinical cancer research to discuss key areas of major current interest. This review presents a meeting report and attempts to provide an impression of the scientific excellence of EACR-19.

Challenges of Cancer Research in Europe — The Case of Translational Research

Challenges of Cancer Research in Europe — The Case of Translational Research

EACR-18: the best of European cancer research

EACR-18 was the 18th biennial meeting of the European Association for Cancer Research (EACR). It attracted more than 700 delegates, providing a pivotal European forum for basic scientists, translational researchers and clinical oncologists alike. It covered most of the key areas and recent developments in cancer research. This Review presents a meeting report.

Critical Review of European Experience with Neoadjuvant Therapy

The use of primary systemic therapy (PST) is being increasingly investigated and not limited to inoperable breast cancer any more. Breast cancer research in Europe has played a crucial role in implementing this concept and continues to be a major contributor to the international scientific landscape with several actively recruiting PST-trials. After the proof of equivalency between PST and adjuvant chemotherapy, numerous trials have been conducted already. Since the treatment can be monitored by individual tumor response, PST is a tool for in vivo chemosensitivity testing and shows pathohistologic complete remission (pCR) to be a good surrogate marker for improved survival. Actively recruiting trials (e.g. trials of the AGO PREPARE and TECHNO) integrate modern concepts of treatment like dose-dense, dose-intensified, sequential therapy and tumor targeting with trastuzumab in PST. The rate of breast conserving therapy after PST is increased by reduction of the tumor size and surgery in the outlines of the tumor does not seem to impair patients outcome. Further trials are needed to elucidate the role of PST in primary breast cancer. The aim of tailoring therapy for the individual patient is consequently pursued by correlation of therapy response to the genetic profile of the tumor with new technologies and will allow improved selection of treatment options in the multimodal approach of modern breast cancer treatment.

New methods to approach immunotherapy of cancer--and strategies of tumours to avoid elimination. Conference report, on behalf of EUCAPS. European Cancer Research Consortium.

Owing to the intense effort of numerous investigators, the number of tumour antigens potentially of use for clinical immunotherapy continues to increase. At the same time, further strategies employed by tumour cells to avoid destruction by the immune system are being uncovered. A combined onslaught to target tumour cells and prevent their "escape" will be required for successful immunotherapy. Progress in this area was the subject of a meeting supported by the European Cancer Research Consortium "EUCAPS", which was held in London in February 2000. This conference was the second of a series, the first of which was summarised previously in this journal [Pawelec G et al. (1999) Cancer Immunol Immunother 48: 214].

Occupational cancer in europe

This monograph summarizes the current research on the epidemiology and prevention of occupational cancer in Europe. Eleven peer-reviewed articles offer a composite view of the current status and future perspectives of this discipline at a time of major economic and political changes in Europe. The monograph includes a brief history of occupational cancer research in Europe and the current burden of cancer from occupational exposure. A large portion of the monograph is devoted to reviews of occupational cancer in various European countries or groups of countries. The first two reviews describe those regions with the strongest tradition of research in the field: the Nordic countries and the United Kingdom. These countries are characterized by high-quality cancer registries and routinely collected information on occupation, e.g., on the occasion of censuses, allowing record linkage studies. Four articles address the situation in the remaining large Western European countries--France, Germany, Italy, and Spain. Although these countries have a strong tradition in occupational health research, with the possible exception of Spain, their epidemiologic research dates back only to the 1970s and 1980s; in recent years, however, research on occupational cancer has expanded considerably. The last two articles of the geographic overview describe the occupational cancer research in the Central European countries and the European territories of the Commonwealth of Independent States. The authors of these two articles critically review the available data on occupational cancer from former Socialist countries and provide reliable information on the extent and amount of occupational exposure to carcinogens. The two final articles of the monograph address specific thematic issues: the importance of asbestos as an occupational carcinogen in Europe and the use of routinely collected data to investigate occupational cancer in women, based on the experience in England and Wales. Despite the heterogeneity of these articles, which reflects to a large extent the differences in quality and completeness of the available data on occupational cancer, they represent an original attempt to provide a systematic overview of occupational cancer research in Europe. This publication is originally a partial result of two projects on occupational cancer in Europe funded by the European Commission, Directorate General XII (grants BMH1-CT92-1110 and BMH1-CT95-1100) and has been expanded to include non-European Union countries.

Introduction: Epidemiologic research and prevention of occupational cancer in Europe.

Research on occupational cancer epidemiology has been an important area of occupational health in Europe since the early studies were conducted in the United Kingdom in the 1950s and 1960s. During the last decade, occupational cancer research in Europe has gained an international dimension and become increasingly interdisciplinary in nature. At present, occupational exposures might be responsible for 13 to 18% of lung cancers, 2 to 10% of bladder cancers, and 2 to 8% of laryngeal cancers in European men; among women these figures are 1 to 5%, 0 to 5%, and 0 to 1%, respectively. A notable aspect of current occupational cancer research in Europe is the decreasing importance of traditional circumstances of high exposure to recognized occupational carcinogens and the increasing importance of new industries, mainly in the service sector where possible cancer hazards are poorly known. In addition, the political changes in Central and Eastern Europe open new possibilities for the investigation of high-exposure circumstances and occupational cancer in women.

The EORTC-Breast Cancer Cooperative Group clinical research programme in early breast cancer. EORTC-BCCG.

The aims of the European Organization for Research and Treatment of Cancer (EORTC) are to conduct, develop, coordinate, and stimulate research in Europe on the experimental and clinical bases of cancer treatment. Along these lines, the EORTC Breast Cancer Cooperative Group, which belongs to the EORTC treatment division, aims at improving the standard of early and advanced breast cancer treatment in Europe through the conduct of large, prospective, randomized, multicenter cancer clinical trials investigating innovative approaches as well as relevant questions regarding optimal surgery and radiotherapy or the optimal integration of these various treatment modalities. This paper reviews the current clinical research programme of this group in the field of "early" breast cancer and briefly alludes to the ongoing efforts of the group in areas such as quality control and translational research. Finally, the EORTC-BCCG has been instrumental in the foundation of the Breast International Group, "BIG", which is a large "intergroup" of existing European and Australian breast cancer research groups. It is hoped that BIG will accelerate the turnover of sufficiently large and well-designed breast cancer adjuvant clinical trials through increasing cooperation between its group members as well as collaboration, whenever indicated, with the American Breast Cancer Intergroup.

New EORTC compounds

(NDDCC) was created with the purpose to establish a comprehensive anticancer drug development program covering all essential preclinical and clinical stages, a task executed by the New Drug Development Office (NDDO). The NDDCC makes selections of new candidates for development and has established guidelines for the formulation of investigational cytotoxic drugs (4), for toxicological studies (13) and phase I clinical trials (9). The NDDO aims at reducing the time lag between drug synthesis and introduction into the clinic, and maintaining an “EORTC Standard of Drug Development”. The NDDO has contact with drug suppliers, it decides which additional tests should be performed, it collects all available (screening) data for a new drug that is under development, and issues Information Sheets. Within the EORTC Screening and Pharmacology Group (SPG), chemists synthesize new compounds, others evaluate them for potential antitumour activity in primary and secondary in vitro and in vivo screening systems. In addition to this type ofdrug development for EORTC, agents are tested in selected models at the request of European national cancer research centers. The Clonogenic Assay Screening Study Group (CASSG) evaluates new drugs using clonogenic and other in vitro methods, and performs studies on tumour biology and normalization procedures. The main emphasis of the Pharmacokinetics and Metabolism Group (PAM) is on analytical methodology, quality control, classical pharmacokinetics, metabolism and formulation. With respect to drug formulation, cooperation exists between the EORTC, CRC and NC1 through the Joint Formulation Working Party. Before clinical evaluation by the Early Clinical Trials Group (ECTG) or the Clinical Screening Group (CSG), sufficiently large quantities of the drugs may be synthesized at the EORTC synthetic laboratory, located at the University of Twente, The Netherlands. Preclinical toxicology studies under strict Good Laboratory Practice (GLP) procedures are performed at TNO, Zeist, The Netherlands. A few examples of compounds that have been developed by the SPG or by national cancer research institutes with the help of the SPG, and that were studied in the clinic by members of the EORTC, are listed in Table 1. Special attention is drawn to their main

The European organization for research and treatment of cancer (EORTC)

The European Organization for Research and Treatment of Cancer (EORTC) was founded in 1962 by research workers in the main cancer research institutes of the Common Market countries and Switzerland. This small group of cancer specialists comprising clinicians and basic science researchers decided to form an association to promote cancer research in Europe through the joint efforts of the clinical and basic research groups of several countries. Among them, were Henri TAGNON from Brussels (Belgium), Silvio GARATTINI, Director of the Institute for pharmacological Research in Milan (Italy), D. VAN BEKKUM, Director of the Radiobiological Institute TN0 at Rijswijk (Netherlands), K. BREUR, Director of the Amsterdam Cancer Institute (Netherlands), G. MATHE, D. SCHWARTZ, and M. TUBIANA from Villejuif (France). Initially the organization was called the “Groupe Europeen de Chimiotherapie anticancereuse” (GECA), 1 year later it became the EORTC and has been known all over the world under this appellation. G. MATHE was its first President from 1962 to 1965. The creation of the EORTC was immediately greeted both by the governments of the various EEC countries and by the medical and scientific circles. From the outset its two main goals were first to develop and coordinate clinical research in Europe and indeed it has organized several hundreds of cooperative multi-center controlled clinical trials and second to promote that area of basic research, which is closed, to providing significant results for diagnosis or therapy. During the past 25 years the EORTC has progressively become the largest organization for therapeutic cancer research in Europe. In 1972, the NC1 in Washington stated that its creation has been “the most important development in therapeutic research on cancer in Europe.” PRESENT STRUCTURES