Nouvelles approches thérapeutiques dans le cancer du sein HER2 positif

For over 10 years, HER2-directed therapy has shown a revolutionary improvement in the prognosis of breast cancer, making such treatment the backbone of the management. Despite the benefit, a resistance process could appear during the treatment and novel therapeutics strategies have been developed and have proved their efficacy. This article describes the therapeutic management of HER2 positive metastatic breast cancer, its therapeutic evolution, and the ongoing clinical trials.     

Nouvelles thérapeutiques ciblées dans les glioblastomes

The efficacy of the standard treatment for glioblastomas (surgical resection combined with radiotherapy and chemotherapy) is so far somewhat limited with a median survival rate of about 15 months. The development of new therapeutic approaches is therefore needed. In recent years, new-targeted drugs have been developed to strengthen the therapeutic arsenal in cancer treatment. Molecular targets are based on the biological and molecular characteristics of the cancer cell, such as hyperexpression of the EGF receptor, activation of the PI3K/Akt and Ras/Raf pathways. Unfortunately, results from glioblastoma trials have been disappointing so far. On the other hand, early clinical results using antiangiogenic agents appear very promising. It can be hoped that in the next few years these agents might transform the dismal prognosis of glioblastomas.     

Nouvelles thérapeutiques du cancer de la prostate métastatique résistant à la castration

Despite that greater knowledge of prostate cancer biology has led to the isolation of many new and promising targets, treatment of metastatic prostate cancer is still challenging. New agents targeting these molecules are currently under development in large randomized phase III trials, to improve overall survival and the quality of life of patients with metastatic castrate-resistant prostatic cancer (CRPC). Cytotoxic chemotherapy (docetaxel-based chemotherapy) demonstrated clinical benefit on overall survival, but could be improved. Drugs targeting directly or not the androgen receptor such as abiraterone or new specific peripheral anti-androgens (MDV3100) are very promising. Bone targeted therapies (endothelin1 receptor A inhibitor, RANK ligant, metabolic irradiation) are also very promising and are in development in large phase III trials. Antiangiogenic therapies could also be effective in CRPC. Autologous vaccin against prostatic acid phosphatase seems to prolong overall survival and other vaccin and immunotherapy strategies are in development (anti-CTLA4 antibody). A recent analogue of thalidomide, probably more efficient, lenalidomide is also in development.     

Kétamine et dépression : vers de nouvelles perspectives thérapeutiques en soins de support ?

Ketamine, a molecule mainly used as an analgesic in supportive oncology in particular in palliative care, turns out to be an excellent fast-acting antidepressant. By acting as an NMDA receptor antagonist, its mechanism of action is complementary to classical and long-acting antidepressants like selective serotonin reuptake inhibitors. These properties offer new perspectives in fast-controlling depression within the development of early palliative care in oncology.     

Les tumeurs de vessie: aspects épidémiologiques et thérapeutiques à Brazzaville

Objectives

To define the epidemiological variables and to appreciate the therapeutic and evolutionary aspects of bladder tumors.

Patients and methods

The study is a retrospective survey of the files of patients hospitalized for bladder tumor in the Department of Urology and Andrology of Brazzaville University Hospital between 1990 and 2006. During this period, 82 patients had been hospitalized for bladder tumor. Only 40 complete files have been used for the survey. The epidemiological, diagnostic, therapeutic and evolutionary aspects have been analyzed.

Results

Bladder tumors are the second most prevalent urogenital tumors after the prostate tumors, with a frequency of 4.78%. The mean age of the patients was 51 (range 23–77) years. The majority of the patients came from the southern part of the country, which is a zone of endemic bilharzia. Hematuria was the main clinical sign. The diagnosis was based on ultrasound and intravenous urography. Anatomopathological examinations performed in 11 patients revealed a predominance of transitional carcinomas of epidermoids. Among the 40 patients, 17 (43%) had been treated surgically, with 4 (23%) recidivisms. Eleven (27.5%) patients died during the period of survey.

Conclusion

Bladder tumors in Congo seem more frequent in the zones of endemic bilharzia.     

Innovations thérapeutiques en radiothérapie du cancer de la prostate localisé

Intensity-modulated radiation therapy, image-guided radiation therapy with fiducial markers and prostate brachytherapy allow the delivery of dose escalation for localized prostate cancer with very low rates of long-term toxicity and sequelae. Nowadays, modern radiotherapy techniques make it possible to shorten treatment time with hypofractionation, to better protect surrounding healthy tissues and to escalate the dose even further. Advances in radiotherapy are closely linked to advances in magnetic resonance imaging (MRI) and/or PET imaging. Functional imaging makes it possible to deliver personalised pelvic nodal radiotherapy, targeting the nodal areas at higher risk of microscopic involvement. In patients with an index lesion at baseline or at failure, MR-based focal therapy or focal dose escalation with brachytherapy or stereotactic body radiation therapy is also currently investigated. MR-based adaptive radiotherapy, which makes it possible to track prostate shifts during radiation delivery, is another step forward in the integration of MR imaging in radiation delivery.     

Mélanome cutané de l’enfant : particularités diagnostiques et thérapeutiques

Skin melanoma is an extremely rare disease at pediatric age and its incidence increases with age. Links with predisposition syndrome exists (giant congenital naevus, xeroderma pigmentosum). Diagnosis is often difficult and distinction between benign or malignant lesion is sometime impossible (Spitzoid naevus, melanocytic neoplasms) leading to the diagnosis of “melanocytic tumor of uncertain malignant potential” (MELTUMP). Atypical features (amelanotic or raised lesions, atypical histotype) are frequent leading to delay in treatment. Diagnosis and treatment require expertise for pathologists and dermatologists pediatricians. Invasive melanomas are of poor prognosis despite recent progress in adult treatment. Early and rigorous treatment of suspect skin lesions is necessary.     

Lymphome de Hodgkin primitif osseux de la région sacrée : un défi diagnostique et thérapeutique

Primary osseous Hodgkin's lymphoma is a very rare entity. Cases reported in the literature are limited with often insufficient initial exploration. We report a new case of a 24 years old patient with a diagnosis of primary osseous Hodgkin lymphoma of the lumbosacral region with extension to the soft tissues, without simultaneous lymph node involvement confirmed both by conventional and metabolic imaging. The patient received a combination chemotherapy (two courses BEACOPP^® and four courses ABVD) followed by radiotherapy of the lombosacral region at the dose of 40 Gy in 20 fractions. Fifteen months after the end of treatment, the patient was in complete remission.     

Cancer colorectal: stratégies thérapeutiques en situation métastatique

During the last 20 years, management for metastatic colorectal cancer has been strongly modified. Advances in the systemic treatment, increased use of metastatic resections, and multidisciplinary approach in a systematic way have improved the overall survival from 14 months in 1990 to 30 months today. Most important studies recently published onmetastatic colorectal disease are reviewed in this article: state of the art for targeted therapies, chronology of drug use, and multiline options for systemic and surgical treatments. The discussion focusses on how to choose the best option on daily practice waiting for molecular pattern of the tumors.     

Modulation de l’immunosuppression par des chimiothérapies et identification de nouvelles cibles thérapeutiques

MDSC (myeloid derived suppressor cells) are immature cells from myeloid origin that accumulate in spleen and tumor bed during tumor growth and that can suppress anti-tumor immunity by various ways. Two chemotherapeutic agents, 5-fluorouracil and gemcitabin, that are commonly used in the treatment of colon cancer and pancreatic cancer, can selectively kill MDSC. Beneficial effects of 5-Fluorouracil and gemcitabin are however temporary. After treatment with those chemotherapies, an activation of the NLRP3 inflammasome is observed in MDSC, due to an interaction between cathepsin B and NLRP3, which leads to the production of IL-1β thus increasing pro-tumor immune responses. IL-1β enhances the production of IL-17 by CD4 T cells which in turn favors angiogenesis and tumor growth.     

Tumeurs épithéliales thymiques : aspects diagnostiques et thérapeutiques

Thymic malignancies are tumors which necessitate a multimodal approach. Twenty percent of these tumors are associated with auto-immune disorders. Surgery remains the treatment of choice for localized lesions. Complete resection represents the main prognostic factor. Postoperative radiation could be considered for patients with residual disease. Chemotherapy is standard in locally advanced and metastatic disease. In current practice the most common regimen for adult patients is anthracycline-based chemotherapy. The combination of carboplatin and paclitaxel seems to be efficient in recent studies and could be used as first-line. Several targeted therapies, such as KIT inhibitors, anti-VEGF, CDK inhibitors, or more recently mTOR inhibitors, have been developed with promising results. In the age of personalized medicine, including patients in phase I studies may help to identify rare mutations and treat them specifically. In France, monthly national web conferences are performed by RYTHMIC (Réseau Tumeurs Thymiques et Cancer) group to optimize the management of these tumors.     

Cancer et grossesse: aspects épidémiologiques et thérapeutiques

Having to start chemotherapy during pregnancy is a rare event. The decision to proceed with this treatment depends on the drugs used, how long the foetus will be exposed to them and the gestational age at the time of exposure. It is important to know the mutagenicity potential of the chosen medicine, and consequently, the risk for the child, without putting the mother’s life or health at risk. This issue mainly involves breast cancer, leukemia and lymphoma. The first trimester of pregnancy is the most critical period for the foetus, as this is when organogenesis occurs. Antimetabolites are the drugs most linked with the risk of malformation. In addition, chemotherapy may have a directly toxic effect on the foetus in utero. Myelosuppression is the most common of these, causing infections and/or foetal haemorrhage. The long term risks of cancer on fertility or the child’s intellectual development are still not well known and must be included in prospective studies, as well as being recorded in a specific data file.     

Applications thérapeutiques non oncologiques des thérapies moléculaires ciblées

Significant improvements in the knowledge of cancer biology have permitted the development of new molecular targeted therapies. Meanwhile, a better understanding of the physiology of various non-cancerous diseases has allowed developing these agents in other areas. This review intends to illustrate these perspectives through examples corresponding to different strategies of molecular-targeted therapies : use of a monoclonal antibody binding a receptor (rituximab and rheumatoid arthritis) or a ligand (bevacizumab and age-related macular degeneration), tyrosine kinase inhibitor (imatinib and systemic sclerosis) or inhibitor of cytoplasmic signal transduction pathways (immunosuppressive and antiproliferative effects of mammalian target of rapamycin [mTOR] inhibitors). Clinical results can draw today what could become molecular medicine of tomorrow.     

Les formes héréditaires du cancer de l’ovaire : particularités clinico-biologiques et thérapeutiques

Hereditary ovarian cancers account for 10% of all cases. Two major syndromes with dominant autosomal transmission are identified. The most common one is breast-ovarian cancer syndrome due to BRCA1 and BRCA2 genes mutations, and the Lynch syndrome with mutated MMR genes is the other. Alterations in homologous recombination specifically observed in ovarian cancer with BRCA defects associated to Parp inhibition create a synthetic lethality of special interest. Numerous studies are in progress to explore this promising new approach. Furthermore, it seems that carcinogenesis of these two syndromes are different, suggesting alternative therapeutic options in the near future in order to improve prognosis of ovarian carcinomas.