memo - Magazine of European Medical Oncology

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0207-6

Tzekova, V.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0186-7

Kurteva, G. P.; Kurtev, P. F.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0195-6

Gastrointestinal stromal tumours are the most common mesenchymal neoplasm of the gastrointestinal tract and are highly resistant to conventional chemotherapy and radiotherapy. The purpose of this manuscript is to present a comprehensive review about the treatment of this relatively new disease. A profound analysis is done concerning the effect of Imatinim mesilat (Glivec) as a therapeutic agent for the treatment of advanced GIST. The predictive role of the mutations in c-kit gene on the outcome of the GIST treatment with Glivec is recognized. In conclusion Glivec® is a highly specific target therapy, which completely has changed the paradigm for understanding cancer. This drug revolutionized the treatment of GIST, achieving three times longer survival comparing with the historical controls.

Kamenova, M.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0194-7

This article is a review of actual consideration on pathomorphological and genetic parameters of GIST associated with their prognosis and prediction to target therapy. GIST are new separate oncological entities with well-determined morphological and molecular biological characteristics with oncogenic mutation of the tyrosine kinase and have good response to blocking tyrosine-kinase therapy. The different grade of malignancy and some deviation from conventional pathology (absence of KIT mutation, appearance of other mutation such as PDGFRA) require implementation of more accurate pathomorphological and genetic prognostic and predictive criteria with the respective changes in standard diagnostic practice. Large-scale studies indicated that the tumour localisation affects the risk of tumour recurrence and progression. Small intestinal tumours are more aggressive than gastric GIST and this should be included as a risk factor. This gave proof supporting the inclusion of the tumour site as an important parameter considered into the risk assessment of resected GIST. New ESMO recommendations for diagnostic procedures, treatment and follow-up include the obligatory site of tumour, its size and mitotic index. The presence of specific mutations has predictive role and the application of mutation analysis has been recommended in metastatic tumours. Many other biological and pathohistological characteristics are being investigated but their prognostic and predictive role has not been proven yet.

Koynov, K. D.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0193-8

The tyrosine kinase inhibitor imatinib proved to be a highly effective therapy in patients with inoperable advanced or metastatic GIST. Furthermore, imatinib is being studied in several clinical trials as adjuvant treatment in GIST patients after radical removal of primary tumour. The data so far are encouraging and have shown that imatinib reduces the risk for recurrence especially in patients with larger tumours. The drug was well tolerated in the adjuvant setting. Nevertheless, in this setting there are still many questions to be answered. It is expected that the data from the clinical trials that are now ongoing will provide in the future the necessary knowledge how to perform the most adequate adjuvant therapy in radically operated GIST patients.

Timcheva, C.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0196-5

The treatment of patients with unresectable or metastatic imatinib-resistant gastrointestinal stromal tumours is a big challenge. Primary resistance and secondary resistance are under investigation. Secondary resistance can develop through various mechanisms, the most common being secondary KIT mutations in clonally expanded cancer cells. Effective standard treatment after failure of imatinib therapy is a small molecule tyrosine kinase inhibitor sunitinib. Its efficacy is associated with the blockade of receptor tyrosine kinase signalling by KIT, PDGFRs, the three forms of the vascular endothelial growth factor receptors (VEGFR-1, VEGFR-2 and VEGFR-3), Fms-like tyrosine kinase-3 receptor (FLT3) and the receptor encoded by the ret proto-oncogene (RET). Sunitinib induced promising activity in a phase III study with imatinib-resistant patients: time to tumour progression 27.3 weeks for the sunitinib arm vs. 6.4 weeks for the placebo arm, median progression-free survival 24.1 vs. 6.0 weeks, objective response rate – 6.8 vs. 0 weeks. Salvage treatments for progressive disease following the therapy with sunitinib show clinical benefit in a minority of patients. ESMO recommends to include these patients in a clinical trial with new targeted compounds and new drug combinations.

Zojer, N.; Ludwig, H.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0187-6

Chronic lymphocytic leukaemia (CLL) in early stages does not require immediate treatment. Although some patients progress rapidly, institution of treatment in an asymptomatic phase has so far not been demonstrated to be beneficial and is best deferred to the time of disease progression. Some early stage patients do not progress for a prolonged period of time and may indeed never need treatment. For patients requiring treatment, risk-adapted strategies have been defined in recent trials. Importantly, age itself should not be used to preclude patients from more intensive protocols, with performance status and presence or absence of co-morbidities being the recommended criteria for treatment adjustments. Whilst fitter patients without significant co-morbidity are initially best treated with immunochemotherapy protocols, aiming at achieving maximum tumour reduction and a status of negativity for minimal residual disease (MRD), less intensive strategies seem to be preferable for the less fit, "slow-go" patient. The CLL8 study has now set the current standard for first-line treatment of the "go-go" patient, showing that rituximab + fludarabine and cyclophosphamide (R–FC) improve not only response rates and progression-free survival as compared to fludarabine and cyclophosphamide (FC), but also overall survival. Currently, studies are ongoing trying to further improve over this standard. For patients with co-morbidity, chlorambucil might still be a valuable treatment option. Initial results of ongoing studies seem to indicate that outcome might be further improved by combination of this drug with rituximab. Combination protocols and lenalidomide are currently investigated for their therapeutic efficacy in "go-go" as well as "slow-go" patients. Cytogenetic and biological characteristics of the disease are also getting increasingly important for treatment selection. Currently, CLL cases with 17p deletion are defined as separate subgroup, with poor response to fludarabine- and alkylator-based chemotherapy protocols and also only poor results achievable by R–FC. For this high-risk patient group, alemtuzumab including combination treatments are recommended and for selected patients, several groups are testing a strategy using allogeneic transplantation with full or reduced intensity conditioning.

Weiss, L.; Greil, R.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0189-4

In recent years clinical management of Immune Thrombocytopenia (ITP) has clearly changed due to the emergence of new therapeutics such as Thrombopoietin Receptor Agonists or Rituximab. These agents have been tested in phase III randomized controlled trials and thereby initiated an impulse for the whole field of ITP. Moreover, in 2009 various publications systematically reviewed current practice, presented efforts of standardization as well as new guidelines for diagnosis and treatment of ITP. This short review is intended to summarize these new developments and to propose an up-dated treatment algorithm.

Hopfinger, G.; Weit, N.; Herling, M.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0191-x

Peripheral T-cell lymphomas (PTCL) comprise a heterogeneous group of lymphatic neoplasms, which originate from mature (post-thymic) T-cells. Although comprising less than 15% of all non-Hodgkin lymphomas (NHL) in adults in Western countries, T-cell lymphomas still pose a considerable clinical challenge. To date, no standard therapy is available for the treatment of these T-cell malignancies. Treatment options that brought about substantial clinical progress in B-cell lymphomas perform only very poorly when used for T-cell lymphomas. With standard chemotherapy such as CHOP approximately 30% of T-cell lymphomas show a primary refractory course and only 35% of patients survive after 3–5 years. Therefore, novel treatment approaches need to be designed and validated in clinical trials. Here we discuss recent data including those presented at the last annual meeting of the American Society of Haematology (ASH 2009). Currently under investigation are new treatment modalities such as immune modulatory drugs, antifolates or histone deacetylase inhibitors. In addition, we present the ongoing trials that incorporate these new modalities.

Spyridonidis, A.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0190-y

Allogeneic haematopoietic stem cell transplantation in humans results in true biological chimeras. Whilst circulating haematopoietic cells become donor genotype after transplantation, other cells believed to remain recipient in origin. It was only recently realized that bone marrow-derived cells may also contribute to non-haematopoietic tissues, suggesting a level of plasticity not previously expected. New concepts in ontogenesis and developmental potential of adult haematopoietic stem cells emerged and called into question the long-standing biological dogma of lineage commitment. Great expectations for novel therapies were engendered both by the scientific and popular press. This review discusses the current status of the heated debate on the "plasticity" of adult stem cells.

Heller, G.; Zöchbauer-Müller, S.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0192-9

Despite the use of new drugs for the treatment of stage IV non-small cell lung cancer (NSCLC) patients, only a moderate overall survival benefit could be reached and the prognosis of this disease is still bad. Therefore, the intensive search for additional, especially targeted, drugs is still ongoing. In recent years evidence has been grown that the insulin-like growth factor type I receptor (IGF-IR) and its ligands play an important role in oncogenic transformation, growth and survival of malignant cells. Thus, strategies have been developed to block this receptor. The most promising concepts include anti-IGF-IR antibodies and anti-IGF-IR tyrosine kinase inhibitors. Currently, most data are available for the monoclonal antibody CP-751,871 (figitumumab). A recent phase II study (Karp et al., J Clin Oncol, 27: 2516, 2009) compared the efficacy and side effects of paclitaxel/carboplatin/CP-751,871 versus paclitaxel/carboplatin in untreated locally advanced or metastatic NSCLC patients. Although the combination of CP-751,871 20 mg/kg with paclitaxel/carboplatin was found to be safe and effective, the following phase III study had to be discontinued. Thus, additional studies are necessary to define the clinical impact of CP-751,871 in NSCLC patients. Other drugs targeting the IGF-IR are also currently under investigation.

Jelic, S.; Popov, I.; Schartinger, V. H.; Sprinzl, G. M.

2010 memo - Magazine of European Medical Oncology

doi: 10.1007/s12254-010-0188-5

Head and neck cancers have for a long time been orphan cancers for any trials of individualized treatment, at least in part because the number of active cytotoxic drugs has been for a long time rather restricted. Histology did not influence treatment modality and the use of particular cytotoxic drugs. Undifferentiated carcinoma of the nasopharynx was the first tumour type to enhance investigations in individualized treatment, as regards to choice of cytotoxic drugs and combinations of chemo and radiotherapy. Recently the HPV16/18 positive carcinoma of the oropharynx has arisen as a topic for individualized approach. The biologicals are relatively late newcomers in the arsenal of drugs available for head and neck cancer. The same statement is related to research of possible targets and thus investigations of subpopulations that might benefit from a particular drug or a particular pathway inhibition. Individualized drug treatment in head and neck cancer appears to be at its promising beginnings.