Gonadorelin analogues (LHRH) are used for the endocrine treatment of prostatic cancer, central early puberty and various gynaecological conditions. Cutaneous adverse events seldom occur. We report a case of injection-site granulomas induced by leuprorelin acetate (Enantone®).

Although female cancer incidence may be on rise, antineoplastic regimens have become more successful. As a result, an increasing number of women with cancer survive to endure the long-term consequences of chemotherapy. One of the most important long-term consequences of cancers treatments in young female is premature ovarian failure and infertility. Because of the increasing survival rates, many of these young women are seeking methods to preserve their fertility. Currently, embryo/oocytes cryoporeservation obtained after ovarian stimulation appears to provide the best fertility preservation option. However, patients may not have sufficient time to undergo ovarian stimulation prior to chemotherapy and/or the hormones used in ovarian stimulation are contra-indicated for estrogen-dependant tumors. In vitro maturation of oocytes (IVM) has been suggested to avoid ovarian stimulation and time requirement in patients with cancer, and can be combined with ovarian tissue cryobanking. In this review, we will discuss the position of IVM in the strategy of fertility preservation in young women.

Trastuzumab has been a revolution in the treatment of breast cancer overexpressing HER. Its use as an adjuvant for a period of 1 year is currently an international standard. Its major toxicity is cardiac, where the systematic monitoring of the LVEF before and during treatment. To evaluate the cardiac safety for our patients, we conducted this retrospective case-control study. The average in LVEF before the start of trastuzumab was 62.5% (51-80), and at the end of treatment 60.55 (40-77), a decrease in absolute value by 2%. This difference is statistically significant with P<0.001. Eighty-three percent of our patients have completed treatment, of whom 26.4% with a provisional arrest because of a regressive fall in LVEF. A final arrest has been made in 17% cases due to either a nonregressive reduction in LVEF or the appearance of symptomatic heart failure found in two patients. Analysis of risk factors toxicity found in this group of patients with a cardiotoxicity persisting an average age and average number of treatments received anthracyclines higher than the rest of our sample, and diminished baseline LVEF. But all these differences were not statistically significants. During the period of monitoring of these patients, six (67%) had spontaneous recovery of their LFEV 5 months ± 2.01 after discontinuation of trastuzumab. For two cases of symptomatic heart failure, they had a clinical improvement under medical treatment in February but is still less than 40%. The cardiac safety in our study seems comparable with the literature data but located in the upper range of levels of toxicity. The lack of statistical power of our study does not exclude a greater cardiac toxicity of trastuzumab among Moroccan women and should prompt a more cautious use of this drug and the achievement of larger studies that could answer this question.

The definition of the optimal dose of a new compound and the design for identifying this dose have been set up for treatment with cytotoxic activity. The optimal dose is typically the Maximum Tolerated Dose (MTD) defined by the occurrence of severe toxic side effects during the first course of treatment. In the era of molecularly targeted therapies (MTA), where the mechanistic relations between the dose, the activity and the toxicity are probably different, how relevant these definitions and designs are?

Intensive use of radio-chemotherapy has greatly improved the prognosis associated with cancer in young girl or women patients. However, improvement of the vital prognosis is frequently associated with impairment of fertility and premature ovarian failure. In vitro fertilization (IVF) followed by embryo cryopreservation is an available method, which needs a partner and a pretreatment stimulation. Ovarian and oocyte cryopreservation are techniques showing great promise. However, the nec plus ultra would be to be able to protect ovaries during chemotherapy. Since more than 10 years Gonadotropin releasing hormone (GnRH) analogues have been investigated as possible means to preserve fertility in young women. However, even recent prospective, randomized studies do not demonstrate clearly their effectiveness. To prevent primordial follicle apoptosis, an inhibitor of tysosine kinase, imatinib, has recently been proposed and positively evaluated in mice. It could represent an interesting hope to preserve female fertility during chemotherapy.

Immunogenic cell death, characterized by calreticulin exposure on the surface of the dying cell, release of the nuclear protein high mobility group box 1 (HMGB1), and release of ATP, enables stimulation of the immune system. We outlined the importance of this kind of cell death for the success of some anticancer chemotherapies. However, defects in the immunogenic cell death signalling pathway can lead to therapeutic failure, apparently because anticancer immune responses must contribute to the efficacy of chemotherapeutic regimens. These defects can be related to the therapy, the tumour cell, the host or the tumour-host interface. It is necessary to characterize these defects to restore and improve the efficacy of anticancer chemotherapies.

The discovery of rapamycin from a soil sample on Easter Island in the mid 60's marked the beginning of an exciting field of research in cell biology and medicine. While it was first used as an antifungal and as an immunosuppressive drug, more recent studies confirmed rapamycin's antiproliferative properties over a variety of solid tumors. Research aimed at identifying its mechanism of action uncovered mTOR (mammalian target of rapamycin), a protein kinase that regulates mRNA translation and protein synthesis, an essential step in cell division and proliferation. Recent evidence suggests a more complex role for mTOR in the regulation of several growth factor-stimulated protein kinases, including the proto-oncogene Akt. This article reviews mTOR function and regulation, and briefly details the future challenges for anti-cancer therapies based on mTOR inhibition.

After an open preliminary study, two double-blind placebo-controlled randomized studies have confirmed the value of per os alitretinoin in the management of severe chronic hand eczema (CHE). The first showed dose-dependent efficacy and a response defined as "clear" or "almost clear" by 53% of the patients receiving 10-40 mg of alitretinoin per day for 12 weeks. In the second multicenter study (the Bach study), comparing the efficacy of a 12-week alitretinoin treatment (10 mg, 30 mg) to placebo for CHE, a "clear or almost clear" result was observed in 17% (placebo group), 28% (group alitretinoin 10 mg), and 48% (group alitretinoin 30 mg). The onset of action was also significantly shorter in the group treated with 30 mg of alitretinoin compared to the group treated with 10 mg. In a study of randomized retreatment versus placebo, 80% of the patients who were initially responders to alitretinoin and whose CHE had relapsed found "clear" or "almost clear" with alitretinoin 30 mg administered for 12-24 weeks compared to 48% with alitretinoin 10 mg. In all the studies, clinical tolerance was comparable and satisfactory, with the most frequent negative side effects being headache, flushing, and mucocutaneous signs identical to those compared with other retinoids. An increase in cholesterol and/or triglycerides was the most frequent biological side effect. Central hypothyroidism, with no clinical expression, was observed more rarely. These studies confirm that alitretinoin treatment can be envisaged as second-line therapy in adults with CHE that does not respond to well-observed treatment with class potent or very potent dermocorticoids.

The different options of fertility preservation must be approached with all patients before initiating any cancer therapy and physicians should refer each patient treated during their reproductive years to specialists in a specialized center that will evaluate the best available alternatives to preserve male and female fertility.The only efficiently proven ways of fertility preservation are sperm cryopreservation for men and embryo cryopreservation to preserve couple fertility. However, the recent progress observed with oocyte cryopreservation (in particular the oocyte vitrification) may change our practices in the future if vitrification is allowed in France. Although the law of Bioethics of 2004 authorizes the ovarian cryopreservation today, its modalities of use stay at present at the stage of the research. But in spite of the low number of published births today in France and in the world, the ovarian tissue cryopreservation is a promising technique. It remains the last possible alternative to protect fertility of prepubertal girls. The sperm cryopreservation must be systematically proposed to all men (even teenagers) undergoing a treatment for cancer potentially harmful for their fertility whatever their sperm quality. The testicular tissue cryopreservation is also a method to be discussed for adults, teenagers in case of failure of sperm banking or for prepubertal boys.

The impact of chemotherapy on a woman's fertility depends on her age and the types and doses of the drugs used. Alkylating agents have the biggest negative impact on ovarian function. A trial is currently examining the use of a GnRH agonist to protect ovarian function. The impact of external radiation therapy and brachytherapy on the ovaries depends on three factors: the patient's age, the dose delivered to the ovaries, and concurrent use of chemotherapy. Ovarian transposition is a simple surgical procedure that can be used in selected cases to reduce the risk of early menopause. Both external and internal radiation has an impact on the uterus, notably by altering its vascularization and by reducing its growth when treatment is delivered during childhood.

Molecular targeted agents represent a major breakthrough in the treatment of non-small cell lung cancer. Among these agents, Epidermal Growth Factor Receptor (EGFR) inhibitors are probably the more important so far. Whether inhibition is obtained by targeting the tyrosine kinase of the receptor (gefitinib or erlotinib) or by using a monoclonal antibody (cetuximab), the place of these treatments will increase in the next years. This article details the role of EGFR in lung carcinogenesis and the main therapeutic approaches used to inhibit EGFR activity. The results of the major clinical trials evaluating these agents are also discussed.

The anticancerous chemotherapies are often responsible for toxic injury of the nontumoral liver. Two types of histological lesions were recently reported during the treatment of digestive cancers: the sinusoidal obstruction syndrome (SOS); or veno-occlusive disease associated with the use of oxaliplatine, and steatohepatitis associated with the use of irinotecan. The SOS is a cause of increased postoperative morbidity, particularly during major hepatectomy or when more than six cycles of chemotherapy are administered. Steatohepatitis increases the postoperative morbidity and mortality. The new targeted molecules do not seem to modify the postoperative course. Hepatic injury and postoperative complications associated with chemotherapies used in the treatment of digestive cancers are summarized in this review.

We report a case of a Pseudomonas aeruginosa septicemia complicated by a septic shock after chemotherapy for pulmonary cancer. Bilateral legs necrotic purpura corresponding to echtyma gangrenosum lesions (erythematous inflammatory halo, positive bacteriologic cutaneous biopsy) was noted 48 h previous to the shock. Echtyma gangrenosum manifestation should alert physician to P. aeruginosa septicemia risk and can be useful to guide probabilist antibiotherapy.

Tamoxifen maculopathy is characterized by perifoveal white refractile deposits associated with pigmentary changes and cystoid macular edema. We report a case of atrophic maculopathy related to tamoxifen in a 70-year-old patient. Fundus examination showed refractile deposits in the macula predominantly in the left eye. Fundus autofluorescence demonstrated foveolar autofluorescence in both eyes. Fluorescein angiogram showed bilateral foveolar hyperfluorescence without leakage in the late phase. Optical coherence tomography disclosed an interruption of the photoreceptor layer in both eyes with a foveolar cystoid space. Multifocal electroretinogram showed bilateral alteration of the foveolar pic. The perifoveal foveolar cyst disappeared on OCT after discontinuation of tamoxifen. This case highlights the usefulness of optical coherence tomography and multifocal electroretinogram in the early diagnosis of atrophic form of tamoxifen maculopathy.

Cetuximab is a chimeric monoclonal antibody selective for epidermal growth factor receptor (EGFR). It is increasingly used in epithelial cancer, often in combination with radiotherapy or chemotherapeutic agents, since it induces a broad range of cellular responses that enhance tumour sensitivity to these therapies. However, it can cause numerous adverse effects, the most common being acneiform eruption on the face and trunk, which is generally bilateral and symmetric.

Senescence was originally described from the observation of the limited ability of normal cells to grow in culture, and may be generated by telomere erosion, accumulation of DNA damages, oxidative stress and modulation of oncogenes or tumor suppressor genes. Senescence corresponds to a cellular response aiming to control tumor progression by limiting cell proliferation and thus constitutes an anticancer barrier. Senescence is observed in pre-malignant tumor stages and disappears from malignant tumors. Agents used in standard chemotherapy also have the potential to induce senescence, which may partly explain their therapeutic activities. It is possible to restore senescence in tumors using targeted therapies that triggers telomere dysfunction or reactivates suppressor genes functions, which are essential for the onset of senescence.

To evaluate the effect of Temozolomide on female fertility and the relevance of our coverage in preservation of fertility.

Sunitinib is an antiangiogenic tyrosine kinase inhibitor indicated in the treatment of metastatic renal cancer and gastrointestinal stromal tumours (GIST). We report a case of leg ulcer apparently triggered by this drug and we discuss the potential implication of the antiangiogenic effect of sunitinib in ulcer genesis.