Antiangiogenic agents are an innovative oral chemotherapy prescribed in metastatic renal cancer and gastrointestinal stromal tumors (GIST). These molecules have several side effects. A woman, with moderate hypertension and severe Thevenard's ulceromutilating acropathy, presented renal cancer with lung metastasis. She was treated by antiangiogenic therapy (sunitinib). Under this treatment, she presented some large, extensive, severe and necrotizing ulcerations of both hands and feet, exacerbated with a sepsis. Sunitinib was stopped and antibiotics were combined with surgical trimming leading to clinical remission and complete healing. Sunitinib inhibits both tumor angiogenesis and tumor cell proliferation, but also the preexisting microcirculation. In our case, severe neuropathy caused neurovascular dysregulation which, together with hypertensive microangiopathy, led to a severe hand-foot skin reaction. This microangiopathy worsened under anti-VEGF therapy. The clinical severity was linked to the severity of the neuropathy. To avoid having serious cutaneous consequences, neuropathy and microangiopathy have to be diagnosed before introducing antiangiogenic therapy.

The rarefaction or loss of eyebrow hair may represent an esthetic complaint or a peculiar finding associated with a given disease. The causal disorders correspond to a few dermatitides and several endocrine, auto-immune, infectious, neoplastic, traumatic, iatrogenic and genetic disorders.

The targeted agents have considerably modified the therapeutic approach of cancer over the last few years. The use of these new agents has been associated with the occurrence of new side-effects among which cutaneous side-effects are the most prominent. Although they rarely compromise the vital prognosis, these cutaneous side-effects must be taken into consideration in order to improve treatment compliance and to maintain an acceptable quality of life. Accurate identification of these cutaneous side-effects is therefore critical to improve the management of these patients. A better understanding of the mechanisms underlying cutaneous signs is also an important issue as it gives us the opportunity to increase our knowledge of the skin pathophysiology. Furthermore, the cutaneous manifestations could sometimes be associated to the antitumor response. The skin is an easily accessible interface, allowing addressing the complexity of the targeted therapies effect on tissues.

Aurora kinases (A, B and C) are proteins expressed only in cells which divide actively and their increase is a factor of bad prognosis in cancer. They regulate the maturation of centrosomes, the separation and the condensation of chromosomes, mitotic checkpoint and cytokinesis. The inhibition of aurora kinases, by powerful and selective inhibitors, is due to the formation of abnormal cells which are eliminated by apoptosis. The purpose of this article is to present the role, the antitumor activity and the tolerability of these inhibitors. They can be administered orally or intravenously, on weekly or monthly schedules. In our knowledge, twelve molecules are evaluated at the present time and will be discussed only the most advanced namely: VX-680, ZM 447439, MLN 8054, AZD 1152, PHA 739358, SU 6668 and AT 9283. The main indications are breast, colon, lung, pancreas and bladder cancers as well as hematologic tumors such as leukemia (ALL, AML, CML) and lymphoma. These inhibitors can be associated with other chemotherapies. They seem well tolerated; the reported side effects are digestive disorders (diarrhea), fever, asthenia, alopecia, slumber, neutropenia, myelosuppression and disturbance of the biological markers.

Twelve years ago, rituximab, a chimeric monoclonal anti-CD20 antibody, became available for the treatment of relapsing follicular lymphoma. It has resulted in an improvement of approximately 20% in survival for nearly all B cell lymphomas. In follicular lymphoma, rituximab combined with chemotherapy is indicated as first-line treatment when treatment is necessary. It is also an interesting option, alone or in combination with chemotherapy for the treatment of relapses, after verifying the persistence of CD20 expression on the surface of malignant cells. As a maintenance treatment after chemotherapy with or without rituximab, it improves relapse-free survival and overall survival. The standard treatment for high-grade diffuse lymphoma, regardless of age and regardless of predicted severity, is now the combination of CHOP chemotherapy and rituximab. The combination of fludarabine, cyclophosphamide, and rituximab is currently the reference treatment for chronic lymphoid leukemia as first-line treatment for patients with few comorbidities and for those with relapses. The role of this antibody in the treatment of more serious forms of lymphoma is under evaluation. The administration of rituximab, alone or in combination, in the treatment of low-grade non-follicular lymphoma must be decided as a function of existing protocols in multidisciplinary consultations. New-generation anti-CD20 antibodies, designed to improve still further the already remarkable efficacy/toxicity ratio, are now taking the road that rituximab opened.

Biotherapy is the use of molecules derived from living organisms, cells, or even tissues for therapy. It is based on the exploitation of recent new insights of various biological mechanisms and relies heavily on a sophisticated cellular and molecular expertise. One of the major tools of biotherapy is currently monoclonal antibodies and derived products, whose are the subject of the present issue. Monoclonal antibodies have become major therapeutic drugs for treating a number of diseases, thanks to a remarkable molecular engineering. The success of the first generation of monoclonal antibodies opens the way to new challenges such as antibody functional optimization, better control of unwanted side effects, or low cost production at an industrial scale. A new generation of antibodies is now emerging and one can already foresee the future: oligoclonal approaches based on the use of specific antibodies cocktails, selection of eligible patients, antibody production at low costs... To date, up to 22 monoclonal antibodies are on the market, with more than two hundred being evaluated in clinical trials.

Since the 1980's, women treated for breast cancer are reporting moderate cognitive impairments during and after chemotherapy. These cognitive impairments may be related to chemotherapy but also to hormone therapy, psychological distress, fatigue... This work is a critical review of the literature, which reports types of impairments, frequency, severity, causes and mechanisms involved in this issue. It also provides an update on potential moderators factors, which may be associated with mild cognitive impairments and various tools for their assessment used in the studies. These studies--selected between 1997 and 2008--show that cognitive impairments are frequently reported by patients with breast cancer but that the mechanisms are still poorly understood and that the methods of assessment are very heterogeneous and difficult to compare. This review indicates that future studies should include more homogenous patient groups, be longitudinal, use more sensitive and specific assessment tools and control moderators factors that play a role in impairment in cognitive function.

Aprepitant is actually recommended in the prevention of nausea and vomiting induced by high emetic risk chemotherapy using cisplatin. We performed an observational prospective study on 101 patients evaluating the efficacy of aprepitant in the clinical conditions of use of cisplatin, out of context of clinical trial. We did not perform any intervention on the choice of anti-emetic treatment by the clinicians. Data on anti-emetic treatments were collected from prescriptions by a pharmacist after prior consultation with a medical doctor. Inclusions were closed when we lay 50 patients who received aprepitant associated to standard anti-emetic treatment (ondansetron and prednisolone) and 51 patients who received standard anti-emetic treatment. We observed a significant positive effect of aprepitant in the prevention of acute (84 vs 74.4 %, P = 0.24) and delayed vomiting (84 vs 60.8%, P = 0.009). But there was not a significant difference between the two groups regarding the prevention of nausea and the rate of complete response (absence of nausea and vomiting during five days).

PI3K/AKT/mTOR is a cell signalling pathway that plays a major role in regulation of apoptosis, cell growth and cell cycle. This pathway is often disregulated in human cancers, and constitutes an interesting target for antitumor therapy. Rapamycin is an inhibitor of mTOR that has first been developed for its immunosuppressive characteristics, as a preventive treatment of graft rejection. More recently, three rapamycin analogs have been developed, resulting in interesting results in preclinical studies on cancer cell lines : temsirolimus, everolimus, and deforolimus. These molecules are being tested in clinical studies, and both temsirolimus and everolimus have demonstrated efficacy in metastatic renal cancers. In contrast, perfosin, an AKT inhibitor, did not prove to be active in clinical studies. Many ongoing studies explore next indications of these drugs, given alone or in combination with chemotherapy or with other targeted therapy. Identification of predictive factors for sensibility to treatment represents another way of research.

The epidermal growth factor receptor (EGFR) is overexpressed in many solid tumors. Its inactivation has an inhibitory effect on the growth and spread of the tumoral cells. It therefore represents an attractive target to treat different cancers. Several molecules have already been registered while others are still under evaluation. One of the common side effects of these therapies is the development of cutaneous toxicities, more precisely a cutaneous rash, sometimes major and distressing. The physiopathology of these cutaneous side effects is poorly understood. Moreover a correlation between the severity of the rash and the tumoral response has been demonstrated in some studies. If this link is confirmed, the rash could be used as a marker for the anti-tumoral activity. This review will summarize the clinical presentations and the current recommendations for the management of cutaneous toxicities induced by EGFR inhibitors.

Elderly persons want to know about their diagnosis and therapeutic alternatives. Feeling in good health before as well as having gone through hard times enhance acceptability of chemotherapy. Possible issues are perceived in a limited but often overestimated lap of life. At this time, actual age is not present in the patient's mind. But as a result of the treatment, patients feel signs of ageing. The repercussions of the chemotherapy, mainly the tiredness, are withdrawal from social life and retreat into the private sphere. Cancer and chemotherapy give rise to a feeling of loneliness and vulnerability never known until this stage. Weakened by the experience, patients feel ageing. Transport difficulties and isolation are two significant consequences. Although patients claim to have taken the decision to be treated on their own, the investment of the closer relatives will prove to be essential during the chemotherapy. One cannot think about chemotherapy for elderly people without integrating psychosocial and economic dimensions from the outset. The geriatric evaluation must be seen as a dynamic approach likely to be modified by integrating new elements at any stage of the patient's treatment.

Management of cancer in the older-aged patient is an increasingly common problem in our occidental societies. Cancer is a disease primarily of older persons: over 60% of all cases of cancer are diagnosed after age 65 - an age group that constitutes less than 20% of the western population and the risk of persons over 65 years of age developing cancer is at least 10 times that of those under 65. Cancer in older persons may be considered a different disease from cancer in the younger in that way that biology of the host could influence the growth of cancer, that the management of the disease deserved an individualized approach. Indeed, the normal process of aging is associated with a progressive age-related reduction in function of many organs, including losses such as renal, pulmonary, cardiac, immune, hepatic, haematological, muscles, osseous, sight, hearing and brain functions. The consequences of these changes with age, added to comorbid diseases, have major implications on toxicities of anti-cancer therapies, surgery, radiotherapy as well as chemotherapy. However chronologic age should not be used as a guide to cancer therapy. Performance status and physiologic performance of the older patient are of prime importance to decide and conduct chemotherapy.

Life expectancy increasing and cancer incidence rising with age, geriatric and cancer care will become a significant medical, public health, challenge. It is possible that the lack of efficacy of cancer therapies in the elderly may simply be due to the fact that physicians reduce anticancer drug doses empirically, in order to avoid "putative" toxicities that might arise as a result of alterations of physiological functions or as a result of co-morbidities generally present within this population. However, many authors have demonstrated that some patients over 70 years old could tolerate and obtain same benefit from therapies as younger adults, when some who are frail need less aggressive therapies. It is imperative that decisions regarding the management of cancer in older persons should be based upon the individual needs and fitness of the patient, and not based on chronological age. The main difficulty is the lack of scientific references on optimal treatment-dosing in the elderly, and we cannot extrapolate, as it stands, the information from younger patient. Indeed, aging is associated with multidimensional changes, including alteration of physiological status, comorbidities and polymedications. These changes may lead to pharmacokinetic (PK) modifications, namely in absorption, distribution, metabolism and elimination of drugs as well as pharmacodynamic (PD) modifications. Prospective studies need to be implemented in the elderly in order to study in depth the PK and PD properties of the drugs used for these patients, and establish PK-PD relationships in this specific population. Such studies have been successfully conducted in the elderly, some of them leading to dose recommendations. This paper detail the different sources of PK-PD variability in the elderly, some practical considerations regarding the design of studies using the population approach, as well as some examples of studies performed in the elderly. We conclude with some recommendations in this population at risk.

The search for a peripheral neuropathy must be systematic when a toxic medicament for the peripheral nervous system is prescribed as well as the search for a drug induced neuropathy is part of the screening of any peripheral neuropathy, but for numerous drugs, the imputability is not strictly demonstrated. A drug induced neuropathy must be differentiated from a neuropathy related to the disease for which the drug was prescribed. It is the case in the course of some cancers and or AIDS. Moreover, the intake of a neurotoxic drug can aggravate a pre-existing neuropathy. Electrophysiological study is important to confirm the neuropathy, to specify the type, more often axonal, and the severity, and also to detect infraclinical signs of neuropathy before the beginning of the treatment. Many of these drug induced neuropathies are reproducible in animals, that is useful to try to diminish the neurotoxicity in human beings. Antineoplastic chemotherapies and antibiotics are most often implicated in drug induced neuropathies.

Carcinosarcomas are rare uterine cancers and carry poor prognosis. Although these tumours usually arise de novo, some cases developed under tamoxifen therapy have been reported. We report two more cases of uterine carcinosarcoma occurring in two postmenopausal patients benefiting from tamoxifen therapy as adjuvant treatment of breast cancer. A review of the literature is undertaken.

Bleomycins are a family of glycopeptides isolated from streptomyces verticillus and exhibiting antibiotic properties. They are commonly included in chemotherapy regimens used to treat patients with Hodgkin's or non Hodgkin's malignant lymphoma, squamous-cell carcinoma or germ-cell tumor. The chemical structure and action mode of bleomycin have been extensively studied, in contrast, the molecular mechanisms of the cytotoxic effects of bleomycin, in vivo, remain poorly understood. Recently, the apoptotics signaling pathway induce by bleomycin was the object of study, of many groups. In this sense, some studies suggested that bleomycin induce in some cells different apoptotic pathway in dose and time depending manner. The sensibility or the resistance to apoptosis induced by bleomycin may explain the sensibility or the resistance of tumor cells to bleomycin. The aim of this review was to describe the machinery of apoptosis induced by bleomycin in tumor cells.

Angiogenesis or new blood vessel formation is a complex and fundamental event in the process of tumor growth and metastatic dissemination. Actually, most of antiangiogenic agents target the VEGF considered like the most potent proangiogenic factor. These molecules directly inhibit VEGF or the kinase activity of its receptor (VEGFR) and represent a significant therapeutic progress in several solid tumors types. First clinical studies of antiangiogenic agents in thoracic and laryngopharyngeal carcinomas have shown promise mainly in combination with other therapies (chemotherapy, other targeted therapies or radiotherapy). Besides common antiangiogenic therapies-induced adverse events, risks of bleeding caused by tumor necrosis mainly in squamous cell lung carcinomas have been observed during early clinical trials. Assessment of surrogate markers of target inhibition could allow a better selection of patients able to benefit from antiangiogenic treatments eventually combined with chemotherapy or molecules targeting others metabolic pathways.