The toll-like receptors are innate immunity receptors which recognise particular exogenous structures in the microorganisms pathogen associated molecular pattern (PAMP) and endogenous structures damage-associated molecular patterns (DAMP). Eleven TLR have been identified among human beings. These are danger receptors located in the cells of the immune system but also in other cells. Their primary function is the recognition of pathogens and the activation of the cell that holds them. It follows from it an action on the cells environment, inflammation cells and an activation of the adaptive immunity. The knowledge of the intracellular signalisation ways of the TLR has allowed us to understand the physiopathology of certain diseases. Thus, several works use the agonists of TLR to stimulate them: vaccines against infectious diseases, allergies and cancers. The antagonists are used to block the TLR in autoimmune and chronic inflammatory diseases. It is clear that the border between innate and adaptive immunity fades and that these two components of the immune response are closely related, thus opening up new prospects diagnostic and therapeutic procedures.

Darbepoetin alfa is an erythropoeisis-stimulating agent that can be given in an every week (QW) or every-3-weeks (Q3W) schedule for the treatment of chemotherapy-induced anemia. We assessed the cost-effectiveness of Q3W darbepoetin alfa compared to QW darbepoetin alfa, from both a health-care and societal perspective in France. Based on a clinical trial design, a decision-tree model with a 16-week time horizon was developed in Excel(R). A probabilistic sensitivity analysis was carried out. The Q3W regimen resulted in lower total costs per patient from the health-care (-180 euro [95 % CI = -461.2;74]) and societal (-243 euro [95 % CI = -588;62]) perspective. Probabilistic sensitivity analysis showed an incremental cost-effectiveness ratio in favor of Q3W treatment from both perspectives. The Q3W schedule is cost saving compare to the QW schedule. It also reduces the burden of the frequent visits for the patients.

Imatinib (Glivec) is a tyrosine kinase inhibitor used to treat certain cases of leukaemia. We report a case of a drug-induced reaction with eosinophilia and systemic symptoms (DRESS) caused by imatinib.

Among antiangiogenic agents, thalidomide is not the most potent nor the most specific even so when venous thromboembolic events have been reported with the prescription of thalidomide in multiple myeloma. This side effect has been related to the antiangiogenic effect of this immunomodulator. In keeping with this observation venous thromboembolic events have been reported in other indications of thalidomide and with thalidomide analogues (Lenalidomide and Actimid). The thrombotic side effects are mostly venous but arterial thrombotic events are also observed with the use of these molecules. With the other and more specific antiagiogenic agents an increase in thrombotic events are also observed. This increase was not immediately evident since the situation in which they are prescribed (metastatic cancers) are already characterized by a high rate of thrombotic events. The prothrombotic effect of antiangiogenic agents are probably linked to an effect on endothelium (decrease of antithrombotic activities and stimulation of a prothrombotuic state). The other sides effects of antiangiogenic agents (hemorrhages, hypertension, proteinuria, microangiotpahia, delay in scaring) are also probably related to endothelial effects. The prothrombotic effect of antoangiogenic agents appears as potentiating the prothrombotic conditions of the disease (myeloma, cancer) and the prothombotic effects of the associated treatments (chemotherapy, high dose corticosteroids, erythropoietin). The increased thrombotic risk linked to prescription of antiangiogenic agents and specially of thalidomide and analogues for multiple myeloma is such that it is recommended to associate a preventive antithrombotic treatment. Some efficacy has been reported with the use of aspirin, oral anticoagulant or low molecular weight heparin. No head to head comparative trial do not allow to prefer one strategy. From published data full dose oral anticoagulants appear to confer the highest hemorrhagic risk and perhaps low molecular weight heparin the best benefit-risk ratio.

Malignant gliomas of which glioblastomas represent the ultimate grade of malignancy are characterized by dismal prognoses because malignant glioma cells present both important proliferation and neoangiogenesis processes and can actively migrate through the narrow extra-cellular spaces in the brain, often travelling relatively long distances, making them elusive targets for effective surgical management. Invasive malignant glioma cells show a decrease in their proliferation rates and a relative resistance to apoptosis (type I programmed cell death) but seem less resistant to autophagic cell death (type II programmed cell death). Autophagic cell death represents an alternative mechanism to overcome, at least partly, the dramatic resistance of glioblastomas to pro-apoptotic-related therapies. Another way to potentially overcome apoptosis resistance is to decrease the migration of malignant glioma cells in the brain, which then should restore a level of sensitivity to pro-apoptotic drugs. We conclude this work with an algorithm showing the optimal current treatment for glioblastoma with the potent future innovations.

In last few years, the topic of nuclear receptor has been developed in the field of hepatology allowing envisaging therapeutic strategies for the most frequent chronic liver diseases. Peroxysome proliferator-activated receptors (PPAR) contribute to wide physiological processes within the liver such as lipid/glucid metabolisms, inflammatory response, cell differenciation and cell cycle. In vitro experiments and animal studies showed that PPARalpha discloses anti-inflammatory property and PPARgamma discloses anti-inflammatory, antifibrogenic and antiproliferative properties in the liver. Main available agonists are fibrates (PPARalpha) used for 20 years in cases of lipid metabolism abnormalities and glitazones (PPARgamma) used since 2000 for type 2 diabetes. In terms of therapy, animal studies and human trials have been conducted in steatopathies. However, clinicians have to be aware of potential specific side effects related to glitazones especially on cardiovascular system.

The aim of supportive care in oncology is to treat the cancer related symptoms and to deal with the side effects of the treatments of the neoplastic disease. The goal of this article is to present a review of the current state of knowledge in this field by successively exposing the achievements of the last few years, the not yet solved problems and the challenges caused by the new therapeutics against cancer. This article will expose the achievements in the control of cancer related symptoms like cerebral metastases, compressive syndromes, denutrition, dyspnea, bone metastases, thromboembolic events and pain. The recent progress in the management of the side effects of chemotherapy were accomplished in treatment or prevention of mucositis, nausea, febrile neutropenia, anemia and cardiotoxicity of the anthracyclines. The unsolved problems in supportive care are alopecia, thrombocytopenia, cancer-related fatigue and cachexia. Finally, these last years saw the advent of many agents of molecular-targeted therapy in medical oncology which currently form part of the current clinical practice. These treatments have their own side effects, different from those of the cytotoxic, hormonal or immunotherapeutic agents. It is necessary to know these side effects and their management in order to provide the best quality of care to the patients who receive these treatments.

High dose methotrexate (HD-MTX) may cause nonhaematological and haematological toxicities. MTX overexposure may be subsequent to administration errors or to delayed renal elimination resulting from MTX nephrotoxicity. The rescue agent carboxypeptidase rapidly hydrolyses MTX to inactive metabolites. However, current criteria for carboxypeptidase use are not well defined. We retrospectively evaluated the number of patients how should have received the drug if the criteria were applied, but who didn't receive it, and analysed their toxicities.

Palmar erythema occurs in a series of physiological and pathological conditions. The first group encompasses hereditary and idiopathic conditions, as well as the time of pregnancy and ageing. The pathological states include some dermatoses as well as hepatic, autoimmune, infectious and paraneoplastic conditions. Medications may also be responsible for palmar erythema, in particular some chemotherapy agents.

This article describes the treatment of acute myeloid leukemia in older patients with good performance status, and then discusses briefly some future therapeutic perspectives.

Medical corrective make up can be applied to hide the adverse effects of cancer treatments. The aim of this study was to evaluate the tolerance and the satisfaction of patients needing medical make up to hide the cutaneous side effects induced by chimiotherapy and to improve self-esteem.

Basic knowledge in oncogenesis has dramatically improved in the last decade providing more recently new drugs for cancer treatment. These new targeted compounds usually act by inhibiting tyrosine kinase activity of one or more than one proteins involved in tumor growth and cancer progression. This pharmacological effect is the result of monoclonal or small molecule action. Many of these new compounds have cutaneus secondary effects. Cancer patients are now facing new toxicity, essentially skin toxicity. The cutaneous side effects observed in the patients depend on the drug. For example, EGFR inhibitors induce acneiform rash whereas multitarget tyrosine kinase inhibitors induce different more complex effects which physiopatholgy is not yet completely understood. The secondary effects that are frequently observed are described is this article. A better clinical long term management of these effects is a clear medical need as of these effects could be surrogate markers of drug efficacy.

The development of molecular targeted therapies requires some specific methodological approaches. Dose-limiting toxicities are rare in phase I studies the maximal tolerated dose is rarely established. On the contrary, the biological active dose is often determined as the dose inducing biological effect on the target without significant clinical toxicity. Several designs of phase II are described (selection phase II, randomized phase II, stratified phase II...). All of them are indicated in specific situations. The discontinuation treatment studies and the validation of biomarkers (as surrogate endpoints or as classifiers) are the two main particularities of phase III studies designed for the assessment of molecular targeted therapies.

Tamoxifen is an antioestrogen widely used in the breast cancer treatment. Its paradoxical antioestrogenic action on breast and its oestrogenic action on the endometer is well-known. Since 1988, few cases of malignant mixed müllerian tumors following tamoxifen were described. We report a new case of uterine malignant mixed müllerian tumor four years after the end of tamoxifen for breast cancer.

Radiotherapy is an essential treatment for many patients with head and neck squamous cell carcinoma. Its association with molecular targeted therapies represents a real progress. Among the recent advances in the molecular targeted therapy of cancer, the applications centred on EGFR are currently the most promising and the most advanced at clinical level. Considering the set of therapeutic tools targeting EGFR, there are at present two well-identified emerging categories of drugs with monoclonal antibodies, on the one hand, and tyrosine kinase inhibitors, on the other. In many preclinical studies, the combination of anti-EGFR drugs with irradiation has led to additive or supra-additive cytotoxic effects. Furthermore, antiangiogenic agents have shown promising results in association with anti-EGFR drugs and radiotherapy. This research effort has recently produced encouraging clinical results in advanced head and neck cancer with combination of cetuximab (an anti-EGFR monoclonal antibody) with irradiation with a significant impact on patient survival. Active and efficient clinical research is currently ongoing to determine the place of molecular targeted therapies in the treatment of head and neck cancer, particularly in association with radiotherapy.

Angiogenesis is a crucial requirement for tumorogenesis, providing oxygen and nutrient supply necessary for tumor growth and metastasis. This is a complex phenomenon regulated by many factors that can now be targeted by novel anti-cancer therapies. Antiangiogenic approaches have shown positive results in clinical trials and are now approved as standard of care in medical oncology. Many clinical trials are evaluating antiangiogenic agents in association with radiotherapy. This review aims to summarize the knowledge useful to the understanding of these novel therapies and their potential in combination with radiotherapy.