memo - Magazine of European Medical Oncology

Hilbe, Wolfgang

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0060-z

Wolf, D.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0061-y

Hess, G.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0062-x

With the increasing incidence of Non-Hodgkin's lymphoma and still substantial disease related mortality, further improvement of therapeutic options is needed. Radioimmunotherapy (RIT) is a targeted treatment with the potential to augment the efficacy of conventional monoclonal antibodies. Out of numerous antibody – radioisotype combinations two have been approved so far: 90Y-Ibritumumab tiuxetan and 131I-Tositumomab. The tolerability of the drugs is excellent and the main side effect is protracted cytopaenia, which occurs 4–8 weeks after the treatment. Limitations of use are reduced bone marrow reserve, higher bone marrow involvement and preceding extensive radiotherapy. Results of initial trials showed promising phase I/II data for a variety of lymphoma entities. Especially in follicular lymphoma subsequent phase II/III studies now have established these drugs as single agent treatment for relapsed disease, with improved response rates when applied at an earlier disease stage. The recently released results of the so-called FIT trial helped us to additionally establish their role as consolidation treatment immediately after preceding cyclic chemotherapy. Current concepts evaluate the benefit of RIT in the context of Rituximab maintenance therapy and high dose therapy. In aggressive lymphoma, clinical efficacy of single agent treatment has been found, but nevertheless the development of the drugs in the context of consolidation treatment or as part of high dose regimens is favoured now. Upcoming results will help to identify the potential of these drugs when applied in entities like mantle cell lymphoma, diffuse large cell lymphoma or marginal zone lymphoma. Taken together, radioimmunotherapy is increasingly part of multimodal treatment algorithms, rather than a substitute for other treatment options. Moreover, given their side effect profile, radioimmunoconjugates are a highly attractive single agent option for patients with restrictions against other anti-lymphoma therapies.

Nagorsen, D.; Rüttinger, D.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0063-9

Despite improved therapeutic options colorectal cancer is still a malignant disease with a high mortality rate. During the last few years immunotherapy has become an important pillar of anti-cancer therapy in general. In colorectal cancer, using monoclonal antibodies (mAB) became daily standard in all lines of treatment. Besides mAb several experimental approaches are tested including therapeutic vaccination or cytokine application. However, no substantial benefit has been observed with these latter approaches. Here, we give an overview on established and selected experimental immunotherapies in colorectal cancer.

Fiegl, M.; Gastl, G.; Hopfinger, G.; Eigenberger, K.; Zabernigg, A.; Schenk, T.; Falkner, F.; Falkner, A.; Sodia, S.; Doubek, M.; Brychtova, Y.; Panovska, A.; Greil, R.; Mayer, J.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0064-8

Alemtuzumab is a humanized IgG1 antibody targetting the CD52 antigen which is primarily present on normal and neoplastic lymphoid cells. In a number of studies, its therapeutic efficacy was shown in the treatment of certain lymphomas including chronic lymphocytic leukaemia (B-CLL). In this indication, it was registered in 2001 with patients refractory towards fludarabine. In 2007, it was also registered as first line therapy in B-CLL patients, for whom fludarabine combination chemotherapy is not appropriate. Alemtuzumab is especially beneficial in B-CLL with 17p deletion, by which its otherwise unfavourable course of disease is improved. In this review, the role of alemtuzumab as antineoplastic tool in lymphoid malignancies and as immunosuppressive tool in autoimmune diseases and in the setting of transplantation is described. Furthermore, results from the Austrian-Czech registry on alemtuzumab therapy in B-CLL are updated.

Greiner, J.; Schmitt, M.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0065-7

Tumour cells can be efficiently killed by specific T cells of the immune system. Targeted immunotherapies require the identification and characterization of appropriate antigen structures. To date, a huge number of tumour-associated antigens (TAAs) have been identified and several attempts try to target these antigens to reduce tumour load or to prevent relapse in solid tumour like lung cancer, prostate cancer or renal cell carcinoma. Several enchanting immunological and even clinical responses have prompted to implement vaccination strategies to haematological malignancies like acute or chronic myeloid leukaemia (AML/CML), myelodysplastic syndrome (MDS), multiple myeloma (MM) and also lymphoma. Several immunogenic antigens associated with leukaemias (LAAs) have been identified in the last years in patients with hematological malignancies like BAGE, BCR-ABL, BCL-2, OFA-iLRP, FLT3-ITD, G250, hTERT, PRAME, proteinase 3, RHAMM, survivin and WT-1. Cellular and humoral immune responses against these LAAs were characterized and clinical trails targeting these antigens were performed. This review summarizes the current clinical peptide vaccination trials targeting LAAs in patients with malignant myeloid diseases.

Zielinski, C. C.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0066-6

Metastatic breast cancer is incurable and treatment decisions are complex. Despite the range of therapeutic agents available and the use of different approaches with these agents, an efficacy plateau had been reached. The development of novel therapies based on a greater understanding of the aetiology of breast cancer has begun to produce unprecedented increases in efficacy. This paper reviews the latest advances in the treatment of metastatic breast cancer, including the established aromatase inhibitors and human epidermal growth factor receptor 2-targeted therapies. The recent introduction of anti-angiogenic therapies, such as bevacizumab, may have even greater impact due to their potential to benefit all breast cancer patients.

Bacher, U.; Kohlmann, A.; Haferlach, C.; Kern, W.; Schnittger, S.; Haferlach, T.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0077-3

Gene expression analyses based on the microarray technique allow the simultaneous investigation of the expression patterns of tens of thousands of genes. Given the enormous genetic variety of the diverse subtypes of acute myeloid leukaemia (AML), microarrays provide promising potential for efficient diagnostics, for a more detailed molecular subclassification, as well as for the characterization of new leukaemia subclasses. Also, gene expression analyses might allow the design of assays being able to predict the response to targeted therapy approaches. The robustness of this method is a further advantage. However, not all so far known subgroups of AML are reproducible by gene expression profiling, and the position of this novel method for diagnostics and for therapeutic strategies in AML has to be further evaluated in prospective studies. This review summarizes the recent developments and the current status of gene expression analyses in AML and discusses perspectives of this novel approach in the future.

Ploner, F.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0067-5

SCLC is a life-threatening disease, typically caused by cigarette smoking. The incidence has been decreasing during the past decades, probably due to changes in smoking habits. The disease is mostly diagnosed in advanced stage and therefore requires systemic treatment and radiotherapy. Chemotherapy is the most important treatment intervention and a combination of cisplatin + etoposide (EP) represents the standard of care. These tumours are very sensitive to primary treatment with remarkable response rates, although usually of short duration due to resistance. Improvement in outcomes is very hard to obtain in this disease, regardless of treatment intervention – as it has been recognised in the past years. The presentations at this year's ASCO on SCLC underline this dilemma: results of 3 large phase III trials investigating alternative combination chemotherapy regimens with irinotecan, pemetrexed and topotecan failed to improve outcome when compared to standard treatment with EP. A further report of a phase III trial underlined the current standard of 25 Gy PCI dose in LD-SCLC complete responders with no additional benefit of a higher PCI dose. Progress in the treatment of SCLC – if any – remains to be slow in the light of the presented results.

Dediu, M.; Hilbe, W.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0068-4

This congress report gives an overview of the most important news concerning lung cancer presented at ASCO 2008 meeting. The most interesting highlights were: (1) For the 1st-line treatment of patients with advanced NSCLC, Cetuximab, added to a platinum-based chemotherapy, sets a new standard and side effects (like acne-like rash) were as expected and manageable. (2) Insulin-like growth factor type I receptor (IGF-IR) in combination with chemotherapy could be an optimistic therapeutic option for NSCLC with squamous cell histology since first results proved a response rate of 72% in this histological subtype. (3) Erlotinib as 1st-line treatment for elderly patients showed encouraging efficacy. (4) For patients without progression after the first line regimen, early introduction of a second line agent is an efficient novel therapeutic option. Further validating studies are warranted.

Eisterer, W.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0069-3

Results of this year's ASCO saw significant steps towards an individualized therapy based upon genetic testing of KRAS. Numerous studies demonstrated that the effectiveness of epidermal growth factor receptor (EGFR) inhibitors is completely dependent upon KRAS mutational status. This led to the approval of EGFR inhibitor therapy in first and late-line therapy only in KRAS wildtype patients at least in Europe. In a retrospective analysis of the CRYSTAL trial Patients with KRAS wild-type tumours who received cetuximab were found to have a 1.2-month longer PFS and a 16% higher response rate compared with those who received chemotherapy alone. Patients with KRAS-mutant tumours who received cetuximab had 0.5-month shorter PFS and a 4% lower response rate than did patients with KRAS-mutant tumours who received chemotherapy alone. In the chemotherapy-only arm, KRAS status did not affect PFS or chemotherapy response. The same pattern of response was observed in the OPUS trial. Patients with KRAS wild-type tumours treated with chemotherapy and cetuximab had a 0.5-month longer PFS and a 24% higher response rate; for those with KRAS mutant tumours (99 patients, 42%), the addition of cetuximab was associated with a 3.1-month shorter PFS and a 16% lower response rate. In the chemotherapy-only arm, KRAS status did not affect PFS or chemotherapy response. The CAIRO 2 trial evaluated the combination of capecitabine (Xeloda), oxaliplatin (Eloxatin) and bevacizumab (Avastin) with or without the addition of cetuximab in patients with metastatic colorectal cancer. Overall, the addition of cetuximab resulted in an inferior PFS (9.6 vs 10.7 months) but did not affect response rate (44% in either arm) or overall survival (OS; 20.4 months). For KRAS wild-type patients (305, 61%), the addition of cetuximab did not affect PFS (10.5 vs 10.7 months). Antibody therapy combining cetuximab and bevacizumab has no clear benefit for patients receiving first-line chemotherapy plus bevacizumab and should not be used outside the context of a clinical trial. Further important topics in this year's ASCO included updates on the use, safety and efficacy of Bevacizumab in the first-line treatment of metastatic CRC as well as in the perioperative setting. Results of the NSABC-07 trials strengthened the role of oxaliplatin in the adjuvant treatment of stage III CRC.

Pall, G.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0070-x

Every year oncologists from all over the world present cutting edge research at the annual meeting of the American Society of Clinical Oncology (ASCO). Pancreatic cancer definitely represents a tumour where basic and clinical research is urgently warranted, as the prognosis for patients suffering from this illness is still very poor and only minor advances have been achieved during the last decade. This article is intended to inform the reader about some of the most important abstracts concerning pancreatic cancer presented at this year's ASCO-Annual Meeting at Chicago, covering the areas of early, locally advanced and metastatic disease.

Wöll, E.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0071-9

Overall survival of patients suffering from gastric cancer is still poor. Two-thirds of patients are diagnosed in a locally advanced stage or with metastatic tumour. But even in patients with operable disease recurrence rate is high. To increase the prognosis of this devastating disease much effort has been put in the development of curative and palliative therapy concepts recently. The aim of this article is to summarize the most important publications at this year's ASCO meeting and to put them into context of current therapeutic strategies.

Braun, S.; Zabernigg, A.; Zeimet, A. G.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0072-8

The 44th Annual Meeting ASCO was held in Chicago and again attracted the attendence of more than 30,000 oncologists from all over the world. All abstracts are published in the J. Clin. Oncol., Vol. 26 No. 15s, Part I of II and are also available at www.asco.org/ASCO/Abstracts+%26+Virtual+Meeting . The following represents an author's subjective selection of the highlights in breast cancer.

Zeimet, A. G.; Reimer, D.; Marth, C.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0073-7

The present report gives the scope of relevant contributions focusing on the treatment of gynaecologic malignancies presented at the 44th Annual Meeting of the American Society of Clinical Oncology (ASCO) held from May 30 to June 3, 2008 in Chicago, Illinois. Some new data will directly influence the routine in gynaecologic oncology, while other data have to await their confirmation in ongoing studies until their clinical impact can be definitively evaluated. Regarding the radiotherapeutic adjuvant management of intermediate-high-risk endometrial cancers, the PORTEC-2 trial clearly demonstrated the non-inferiority of vaginal brachytherapy (VBT) as compared with external beam radiotherapy (EBRT) of the whole pelvis with regard to disease-free and overall survival and revealed a higher rate of treatment-related complications and side-effects for EBRT and consequently a higher quality of life in patients treated with VBT. In chemotherapeutic management of advanced and recurrent cervical cancer the four-armed GOG 204 trial demonstrated the best therapeutic index for the cisplatin-paclitaxel regimen. Hence, the authors advocated that this doublet should be used as a control arm in further GOG protocols investigating this setting. Fundamental changes in the routine first-line chemotherapy for ovarian cancer should be expected from the outcome of the phase III Japanese Gynecologic Oncology Group trial that revealed a survival benefit for weekly dose-dense administration of paclitaxel as compared with standard three-weekly carboplatin-paclitaxel.

Willenbacher, W.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0074-6

At the haematological sessions of ASCO 2008 major progress was reported with regard to multiple aspects of haematologic neoplasia. Highlights included the emerging role of JAK2 inhibitors in CMPD, oxametaxine as a new treatment in CML and the differential management of TKIs in refractory or relapsing CML corresponding to mutational status and comorbidities. Demethylating agents increased their share in up-to-date treatment of myelodysplasia based on the followup of several Phase III studies. In multiple myeloma the 4-year landmark analysis of the ECOGE4A03 study further questioned the role of high dose therapy and autologous transplantation compared to Lenalidomide/low dose Dexamethasone induction therapy. Multiple new therapeutic antibodies (e.g. Lumiliximab) as well as better tolerated chemotherapeutics (e.g. Bendamustin) were the cornerstone of presentations in low-grade NHL and CLL. In general the reasonable refinement of targeted therapies is coming of age.

Zach, O.; Zellhofer, B.; Födermayr, M.; Kasparu, H.; Girschikofsky, M.; Hehenwarter, W.; Hauser, H.; Függer, R.; Havlicek, W.; Lutz, D.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0075-5

PURPOSE: The prognostic relevance of circulating tumour cells (CTC) in blood of metastatic breast cancer patients was evaluated and compared with established prognostic criteria. PATIENTS AND METHODS: Blood samples from 119 breast cancer patient were examined in a retrospective analysis. For the detection of CTC in blood, a nested RT-PCR assay for mammaglobin mRNA was applied. RESULTS: In 42/119 (35%) patients CTC were detected. Patients with CTC positive blood samples at the time of diagnosis of metastases lived significantly shorter (median 18 months) than CTC-negative patients (median 51 months), suggesting that CTC serve as an additional prognostic parameter. CTC in blood were an independent prognostic parameter, associated with the highest risk of death compared to other risk factors examined (HR: 2.9). In addition, the appearance of CTC in blood of metastatic patients during treatment indicated poor prognosis. CTC-positive patients had a significantly shorter survival compared to patients remaining CTC negative during followup (p < 0.01). CONCLUSIONS: CTC at the time of diagnosis of metastases are an independent prognostic factor for overall survival. During therapy, the detection of CTC is predictive for a shorter survival of patients with metastatic breast cancer.

Kurtev, V.; Greil, R.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0076-4

Advances in the fields of cellular, molecular biology and immunobiology are opening a wide range of diagnostic and therapeutic approaches towards optimally tailored management of cancer patients. The ever-increasing armamentarium of the state-of-the-art molecular, genetic and immunological tools for the diagnosis, risk determination, treatment stratification and molecular follow-up of individual cancer types results in high challenges for knowledge and experience of medical oncologists and their need for cooperation with other disciplines in a fine-tuned network of specialists. Within this background the Arbeitsgemeinschaft medikamentöse Tumortherapie ("AGMT") has been founded as an academic study group focussed on enabling a series of aims for participating study groups: (i) to maintain and improve the possibility to carry out innovative investigator-initiated trials in medical oncology and haematology, (ii) to give guidance to clinicians and allow patients' access to modern treatment options in rapidly developing fields of cancer therapy, (iii) to allow highly innovative phase I and II treatment approaches, (iv) to make the access to industry-sponsored trials easier and (v) to facilitate cooperation between medical oncologists and other specialists involved in the care of cancer patients. Meanwhile in 20 years of activity in the field of oncologic clinical research, a number of academic clinical trials have been successfully conducted, leading to both publications in peer-reviewed journals and presentations at major international conferences. During the last two years, the AGMT has set out to significantly increase its research portfolio with studies in solid cancers and haematology, while at the same time accomodating changes in the regulatory environment and increased responsibilities for sponsors of academic clinical trials arising from the implementation of the EU Clinical Trial Directive into national legislation.

2008 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-008-0078-2