Pemetrexed (Alimta(®)) is a new-generation antifolate used to treat malignant pleural mesothelioma and non-small cell lung cancer (NSCLC). We report two cases of a new toxicity induced by pemetrexed: scleroderma-like induration of the lower extremities.

As a result of advances in oncologic treatment, a growing number of women diagnosed with cancer may envisage cure. Young women diagnosed with cancer often have a desire to fall pregnant in the future or may even be diagnosed with cancer in the process of family planning. The potential gonadotoxic effect of certain chemotherapeutic agents is well described. Therefore, it is essential that all women concerned about their fertility receive counselling from a reproductive medicine specialist to discuss the fertility preservation options. Currently, ovarian stimulation with cryopreservation of oocytes or fertilized oocytes is the treatment of choice. However, other options such as in vitro maturation or ovarian tissue cryopreservation should be discussed if ovarian stimulation is contraindicated.

Hereditary angioedema (HAE) is a rare disease, which shows a preponderance of female sufferers. There are various types of HAE, with or without C1 inhibitor deficiency but estrogens may worsen the course of the disease in all the types. It is thus mandatory to know this sensitivity to estrogens in order to improve the management of women with HAE during their child-bearing ages. Contraceptive progestin can help to reduce the frequency and severity of the attacks. Pregnancies can be associated with worsening or improvement. Some other situations where endogenous or exogenous estrogens concentration can increase are possibly associated with an aggravation of the attacks (ART, tamoxifène).

Catheter-related infection by non-tuberculous mycobacteria is rare but difficult to diagnose and the treatment is not standardized.

Intravesical therapy with bacillus Calmette-Guérin (BCG) has proved to be effective in the treatment of superficial bladder tumors. Side-effects include local infections and rarely disseminated BCG infection with multiple end organ complications such as granulomatous hepatitis, pneumonitis, aortitis and bone marrow involvement.

Acantholytic dyskeratosis under BRAF inhibitors are dermatological diseases rarely reported to date.

Febrile neutropenia (FN) is a severe chemotherapy side effect. Hospitalization is recommended for FN episode of high-risk (HR) of complications. Management of FN at lower risk of complications remains unclear.

Drug-induced infiltrative lung disease may manifest as variable clinical radiological patterns, including subacute or chronic interstitial pneumonia, pulmonary fibrosis, eosinophilic pneumonia, organising pneumonia, pulmonary edema, or sarcoidosis. A large amount of drugs have been incriminated, including those used in cardiovascular diseases (amiodarone, statins and angiotensin converting enzyme inhibitors), antibiotics (minocycline, nitrofurantoin), most of anticancer drugs (and especially chemotherapy and chest radiation), treatment of rheumatoid arthritis, as well as more recent drugs. A high index of suspicion is therefore required in any patient with infiltrative lung disease and the web-based tool www.pneumotox.com will help to list possible causative drugs. The following steps are necessary: history and timing of drug exposure, clinical and imaging pattern, exclusion of other causes of infiltrative lung disease, improvement following drug discontinuation. Rechallenge, dangerous, is not recommended.

Despite significant progress in the discovery and design of drugs, the interindividual variability to the standard dose of a given drug remains a serious problem in clinical practice. In the future, the aim of pharmacogenetic is to provide new strategies for optimizing drug therapy, both in terms of efficacy and safety. The clinical validation of an increasing number of pharmacogenetic tests, as well as the development of new highly efficient technologies should further promote pharmacogenetics in clinical practice and lead to the optimization and individualization, before treatment, of drug therapy. Therapeutic drug monitoring is a valid tool to determine the pharmacokinetic of a drug and individualized drug therapy, adjusting patient's dose requirement through the measurement and interpretation of drug concentrations. Thus, phenotyping and genotyping tests are now available that determine or predict the metabolic status of an individual and enable the evaluation of risk of drug failure or toxicity. Based on clinical applications, this review focuses on interest of pharmacogenetics, in combination with anticancer agents TDM, on the individualization of treatments used in oncology.

In Switzerland, as in other Occidental countries, the prevalence of arterial hypertension (AHT) in the adult population is around 30-40%. Among the causes of secondary AHT, drug induced hypertension is sometimes omitted. Many molecules can induce AHT or worsen it due to an interaction with anti hypertensive drugs. Among these, NSAIDs and anti depressants, widely prescribed, should be used with caution, particularly in patients at risk, namely: those with preexisting AHT, the elderly, or patients suffering from kidney disease, diabetes, and/or heart failure. Increases in blood pressure have also been described with anti-vascular endothelial growth factor (VEGF) drugs, used in the treatment of (metastatic) cancer. A thorough anamnesis of drugs, including over the counter ones, should be performed in every hypertensive patient, and can avoid cumbersome and unnecessary investigations and therapy.

Medullary thyroid cancer (MTC) is a rare cancer. Vandetanib, a RET tyrosine-kinase inhibitor, significantly increased progression free survival and is the first treatment approved in France for unresectable, locally advanced or metastatic MTC that is symptomatic or progressive. Most frequents adverse events are diarrhea, folliculitis and asthenia. The prolongation of the QT interval on electrocardiogram is frequent but in the most of cases not clinically relevant. A good selection of the patients who could benefit from this treatment and management of side effect are important for the risk-benefit assessment.

Sunitinib was the first targeted therapy improving progression-free survival (PFS) and overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) in the first line of treatment. Classically, sunitinib is administered at a dose of 50 mg/day during four weeks followed by two weeks off (schedule 4/6). This schedule has two pitfalls: intermittent exposure with two weeks "off" and the increase in toxicity during the fourth week. Several alternative prescription schedules were studied with the aim of limiting the intensity of toxicity while maintaining efficacy. This review summarizes the published data on alternative schedules of sunitinib in terms of safety and efficacy. All articles and abstracts on alternative schedule of sunitinib in the mRCC were reviewed. Clinical trials were also searched. Studies evaluating the continuous schedule have not provided evidence of its superiority compared to the 4/6 schedules in terms of activity, tolerance or dose-intensity. Retrospective data of patients treated in a schedule two weeks of treatment "on" one week "off" (schedule 2/3) with sunitinib 50 mg/day show PFS that seem superior to those obtained with a schedule 4/ 6, while having a better safety profile. The alternating schedule of sunitinib 2/3 (50 mg/day) may be a better alternative to schedule 4/6 in terms of tolerance. If toxicity occurs with 50 mg/day on a schedule 4/6, it would probably offer a better alternative in terms of efficiency than dose reduction. The results of ongoing and future studies are expected to prospectively validate the concept.

The international phase IIIb study, ATHENA assessed the combination of bevacizumab/taxane-based chemotherapy in the first-line treatment of HER2 negative metastatic breast cancer (mBC) in real-life setting. Among the 365 patients included in France, median overall survival (OS) is 28.4 months (CI95% 24.8-33.0), with a median time from treatment start to end of study of 36,5 months (25,1-45,4). Exploratory analyses in three sub-groups show that the median OS in long responder patients (not progressing for at least one year; n = 116) is not reached. In responder patients (n = 308), median OS is 33.0 months (CI95% 28.6-37.4) and 12.4 months (CI95% 11.2-17.4) in non-responders (n = 41). In patients with mBC expressing hormone receptors (HR+), treated with first-line hormone therapy before inclusion (n = 87) median OS in is 23.2 months (CI95% 19.6-28.6), and 35.3 months (CI95% 32.2-not reached); P = 0.004 in patients treated first with chemotherapy + bevacizumab (n = 179). The safety analysis in the various sub-groups of grade 3-5 adverse events of particular interest to bevacizumab of this study was comparable to the safety data of randomized phase III studies.

More than 100 drugs have been registered as inducing subacute cutaneous lupus erythematosus (SCLE). Recently, some types of chemotherapy have also been incriminated. If SCLE develops in a setting of neoplasia, two possibilities should be considered: it is either a paraneoplastic syndrome or it is caused by the chemotherapy, thus calling for important decisions on the benefit/risk of stopping potentially effective medication. We report a case of SCLE induced by Xeloda (capecitabine).