memo - Magazine of European Medical Oncology

Gastl, G.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0014-5

Hilbe, Wolfgang; Gunsilius, Eberhard

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0001-x

Zielinski, Christoph

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0002-9

Gehling, U. M.; Ergün, S.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0003-8

Tissue growth is highly dependent on the supply of oxygen and nutrients. This regulatory mechanism does not only apply to normal tissue but also to tumour tissue. In contrast to normal tissue, a tumour at the initial stage is not vascularised. Thus, further expansion requires that the tumour creates its own blood vessel supply. In this context, it is well established that tumours can induce capillary sprouting from pre-existing, surrounding vessels. For many years, it was believed that tumour vascularisation is exclusively due to this process. However, recent studies have revealed complementary mechanisms and processes, such as intussusceptive angiogenesis and postnatal vasculogenesis, as well as alternative mechanisms, like vessel co-option and vasculogenic mimicry. Furthermore, several cellular and molecular mechanisms mediating the switch from a non-angiogenic to an angiogenic phenotype have meanwhile been identified and targeting key molecules has become a novel strategy to treat malignant diseases. This review briefly summarises the current knowledge on molecular and cellular aspects of tumour vascularisation to emphasise the complexity of the vascularisation process.

Stöger, H.; Hegenbarth, K.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0004-7

Therapy of metastatic breast cancer is still palliative with a very low probability to induce complete remission and definitive cure of disease. The relevant efforts of basic research to identify the key and selective molecular alterations, which sustain breast cancer growth and progression allowed developing specific molecular target treatments. Angiogenesis, the process of new blood vessel formation, is required for tumour growth and metastasis. There is substantial preclinical and clinical evidence supporting the central role of angiogenesis in tumour formation and metastasis. Thus, the inhibition of angiogenesis may provide an effective treatment for patients with advanced breast cancer. Several chemotherapeutic and hormonal agents routinely used in cancer treatment have antiangiogenic properties. Novel antiangiogenic agents targeting the vascular endothelial growth factor ligand and receptor tyrosine kinase inhibitors are being developed. Recently, a large phase III clinical trial demonstrated a significant benefit in progression-free survival with the addition of anti-VEGF monoclonal antibody bevacizumab to paclitaxel for first-line treatment of advanced breast cancer. This study established that antiangiogenic therapy is effective in advanced breast cancer, and additional studies of antiangiogenic agents are under way. This review provides an updated overview of the role of angiogenesis in breast cancer pathogenesis, the challenges of developing antiangiogenic agents, and current agents in clinical trials.

Grossi, F.; Brianti, A.; Defferrari, C.; Pronzato, P.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0005-6

Though chemotherapy remains a mainstay of non-small cell lung cancer (NSCLC) treatment, its efficacy has probably reached a plateau. The management of advanced NSCLC has evolved considerably in recent years due to a progressive understanding of tumour biology and the identification of promising molecular targets. Bevacizumab is a monoclonal antibody targeting vascular endothelial growth factor (VEGF), a key signalling protein in tumour neoangiogenesis, growth and dissemination. The finding in study E4599 of a survival benefit for carboplatin-paclitaxel plus bevacizumab over chemotherapy alone led the U.S. FDA to approve the novel combination for the first-line treatment of patients with advanced, non-squamous NSCLC. This study is the first to show a survival advantage with the addition of a targeted agent to chemotherapy in this setting: in particular, for the first time the survival of NSCLC patients has been extended beyond one year. Recently, in a randomised phase III trial, patients receiving cisplatin-gemcitabine plus bevacizumab experienced a significantly longer progression-free survival compared to the standard arm. Based on these data, the EMEA has just issued a positive opinion to extend the drug's indication to include first-line treatment – in combination with any platinum-based chemotherapy – of advanced, non-squamous NSCLC. The aim of this review is to provide an overview of the evidence supporting the emergence of this new treatment. Key questions – including the optimal dose of bevacizumab, safety of the drug in special populations, the selection of patients most likely to benefit from the treatment, the role of maintenance – are addressed.

Hilbe, W.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0006-5

The present report gives a scope on relevant abstracts presented at the 12th World Conference of Lung Cancer held in Seoul, South Korea, in September 2007. Some data will directly influence the daily routine of thoracic oncologists. The most important is the intention of the International Association for the Study of Lung Cancer IASLC to modify the staging system. For example, T4 tumours with satellite nodules will be reclassified as T3, and nodules in the ipsilateral lung from M1 to T4. In the first-line treatment of stage IIIB/IV patients the combination of cisplatin/pemetrexed was equally effective as the control arm applying cisplatin/gemcitabine with a lower rate of side effects. Interestingly, patients with adenocarcinomas and large cell carcinomas showed a significant survival benefit using the new combination which might be explained by divergent enzymatic activity between the histological subtypes. Gefitinib, applied in the second line setting, showed similar efficacy when compared with docetaxel, even in a non-Asian population. Maybe, the gefitinib story has now to be discussed again. The knowledge on predictive markers for an individualised application of targeted therapies is improving, but at the moment this does not influence our daily practice. The role of smoking in lung cancer was discussed in the presidential session. It was stated that the dramatic increase of adenocarcinomas in relation to other NSCLC subtypes is consistent with the hypothesis that changes in cigarette design and composition were the major factors responsible for this development. The use of filter vents reduced the resistance to draw allowing smokers to take bigger, deeper puffs thus facilitating the delivery of smoke particles deep into the airways. In conclusion one can say that the international effort to improve lung cancer outcome is effective, however, the clinically relevant steps are still small.

Dubsky, P.; Gnant, M.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0013-6

During the San Antonio Breast Cancer Symposium 2007 some of the large prospective randomized trials reported failed to show clear-cut advantages of chemotherapeutic regimens that are considered to be more aggressive than standard therapy. Molecular profiles of breast cancer have allowed us to create standardized tools that make response prediction in several patient subsets possible. Although none of the new technology can be recommended for daily clinical practice, future trial design should implement some of the newly gained rationales at its best. Furthermore, tissue collection during the production of clinical trials should be considered mandatory in order to carry out translational research. Clearly, breast cancer research has moved from an era focusing on a treatment stratification largely determined by risk to an acknowledgement of disease heterogeneity requiring a prediction of response before therapy is assigned.

Heinemann, V.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0007-4

Progress in the treatment of advanced pancreatic cancer occurs at small incremental steps. Adjuvant chemotherapy has become a widely accepted standard of care in resectable pancreatic cancer and has a positive impact on survival. Treatment of locally advanced non-metastatic pancreatic cancer is more controversial. First results indicate that secondary chemo-radiotherapy (CRT) may be beneficial in patients who respond to initial chemotherapy. In metastatic pancreatic cancer chemotherapy with gemcitabine is a widely accepted standard of care. Among a multitude of combination therapies, only the combination of gemcitabine plus erlotinib has been registered for the treatment of pancreatic cancer. Further progress is expected from the exploration of new targeted agents, their integration into new concepts of chemotherapy, and the definition of predictive factors which may help to choose adequate treatment strategies for selected patient subgroups.

Ribatti, D.; Vacca, A.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0008-3

While it is well established that the growth of solid tumours is angiogenesis-dependent, it had assumed that leukemias and other haematological malignancies were not. The role of angiogenesis in growth and survival of these tumours has only been realised in the past 10 years. This review summarises the literature concerning the relationship between angiogenesis and disease progression of several haematological diseases. It is becoming increasingly evident that agents which interfere with blood vessels formation also block tumour progression and accordingly, anti-angiogenic therapy has gained much interest as a potential adjunct to conventional therapy for many haematological tumours.

Pirker, R.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0009-2

Chemotherapy-associated anemia affects many patients with cancer and can effectively be treated with erythropoiesis stimulating agents (ESAs). ESAs increase Hb levels, reduce the risk for transfusions and improve the quality of life of anemic patients with chemotherapy-associated anaemia. ESAs are generally well tolerated. Important side effects are hypertension and thromboembolic events either of which occurs in less than 10% of the patients. Although several meta-analyses of controlled clinical trials did not demonstrate a statistically significant impact of ESAs on survival, further research on the association between ESAs and clinical outcome including survival is warranted.

Zabernigg, A.; Erdel, M.; Schranzhofer, R.; Berek, K.; Gattringer, K.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0010-9

We present a rare case of a patient with chronic eosinophilic leukemia, who did not develope the well known organ involvements of the heart, lungs, the skin or nervous system, but who suffered form atypical thrombotic complications including a life threatening sinovenous thrombosis. His disease showed a rapid response to a very low dose of imatinib an the complete remission of a complex cytogenetic abnormality.

Giovannini, M.; Gregorc, V.; Viganò, M. G.; Roca, E.; Lazzari, C.; Spreafico, A.; Belli, C.; Citterio, G.; Rossoni, G.; Donadoni, G.; Corti, A.; Villa, E.; Cappio, F. C.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0011-8

Targeted delivery of TNF to tumour vessels has been achieved by coupling this protein with the CNGRC peptide, an aminopeptidase N (CD13) ligand that targets the tumour neovasculature.The so-called NGR-TNF enhances the penetration of chemotherapeutic drugs in tumours and improves their efficacy. Here we describe a case of hepatocarcinoma which showed response to NGR-hTNF in combination with doxorubicin, clinically proving this promising strategy.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0012-7