When requesting a blood level measurement in the context of "Therapeutic drug monitoring" (TDM), numerous aspects have to be considered in the pre-analytical and analytical area, as in the integration of associated clinical data. This review presents therapeutic classes for which a clinical benefit of TDM is established or suggested, at least in some settings. For each class of drugs, the main pharmacokinetic, pre-analytical, analytical and clinical aspects are evaluated in the scope of such a monitoring. Each step of the TDM process is important and none should be neglected. Additional clinical trials are however warranted to better establish the exact conditions of use for such a monitoring.

Requesting a blood level measurement of a drug is part of the global approach known as "Therapeutic Drug Monitoring". Diverse situations require this monitoring approach, such as inadequate response to treatment or organ failure. Every drug however does not possess all the characteristics for a TDM program. The therapeutic range of a TDM drug has indeed to be narrow and its interindividual pharmacokinetic variability to be wide. As the development of new drugs is currently slowing down, the precise management of existing treatments certainly deserves progress, but needs however to be applied rationally, starting from a valid indication to blood sampling, and ending with a sound dosage adaptation decision.

At the time of diagnosis, central nervous system (CNS) involvement is identified in less than 10% of adult acute lymphoblastic leukemia (ALL). Long-term disease-free survival can be achieved in these patients. CNS disease at presentation does not appear to be an independent poor prognostic factor. In CNS leukemia, innovative treatments and alternative delivery techniques are, however, warranted. Outcome in such patients is a reflection of an aggressive systemic and CNS-directed therapy. However, CNS toxicity represents the dose-limiting side effect of treatment. With effective CNS prophylaxis including intrathecal chemotherapy, high-dose systemic administration of certain agents and cranial irradiation, most adults with ALL without CNS disease at diagnosis may remain free of CNS leukemia. CNS involvement at the time of relapse occurs in 1 to 15% of cases. Leukemic relapse remains a major therapeutic challenge. Adult ALL with CNS recurrence remains of poor prognosis and is generally associated with a systemic and medullary relapse.

Cellular proliferation and drug detoxification are controlled over the 24h by the circadian-timing system, whose disruption can favor malignant processes. Thus, prolonged shift work appears to increase the risk of breast, colon or prostate cancer. Alterations in circadian physiology and/or molecular-clock genes accelerate cancer progression in experimental models and in cancer patients. In addition, anticancer treatments can also dampen or reinforce the circadian-timing system, as a function of dose and time of administration. The adjustment of anticancer-drug delivery to the circadian-timing system (chronotherapeutics) has allowed to reduce five-fold the incidence of severe adverse events as compared to constant rate infusion or wrongly-timed chronomodulated delivery in cancer patients. In experimental models, the best antitumor efficacy is usually obtained following treatment delivery near the least toxic time, a statement that also seems to apply to patients. Dedicated technologies include programmable in time pumps and rhythm monitors and are required for chronotherapeutics. Recent results have revealed that the optimal chronotherapeutic schedule could differ as a function of gender and circadian physiology. In conclusion, the circadian-timing system was shown to negatively control malignant proliferation via partly identified molecular mechanisms. The components of the circadian-timing system thus constitute new potential therapeutic targets in oncology. Mathematical models help toward a better understanding of the role of variability for the determination of the optimal chronotherapeutic schedule and constitute useful tools for the personalization of cancer chronotherapeutics.

There are gene polymorphisms which can impact on the pharmacodynamics of anticancer agents used in the treatment of colorectal cancer. It is the case for thymidylate synthase, for methylenetetrahydrofolate reductase and for UGT 1A1. Polymorphisms of UGT 1A1 are considered as potential indicators of a risk of toxicity treatment by irinotecan. Clinical trials are in progress so as to validate the clinical usefulness of these germinal genetic analyses so as to select treatments/doses adapted to individual profiles.

Colorectal cancer is the 2nd cause of cancer related death in industrialised countries. 20% of all patients present with metastatic disease at diagnosis and need systemic treatment. Since the introduction of irinotecan and oxaliplatin as part of standard chemotherapy, and recently the new targeted agents bevacizumab, cetuximab and panitumumab, the overall survival for patients suffering from metastatic colorectal cancer (mCRC) has increased significantly and nearly reaches 2 years nowadays. Surgery or radiofrequency ablation has become central in the care of metastatic disease. This article resumes recent therapeutic advances in the field and emphasizes the multidisciplinary concertation between specialists to obtain the best outcome.

It become usually after 4 to 8 courses of treatment. A long platin free interval is an increased risk of reaction. Clinical manifestations are various and can be separate in light to mild or severe reactions. Diagnose is retrospective with results of skin test. Prick test and IDR (using sequentially diluted platin salt and delayed reading) are the most available, essentially in case of acute reaction (<2h after injection of platin salt). IDR realized 30 min before injection of platin salt can be a good predictive test of hypersensitivity reaction. Management of this adverse effect depends on clinical manifestation: light to mild: careful re-introduction with a desensitization protocol; severe: no re-introduction. If it's necessary, careful replacement by another platin salt can be possible, eventually in accordance with results of IDR to all platinum salt.

Lung cancer is a bad prognostic illness with a limited survival and many side effects related to treatment used. Supportive care in cancer attends to enhance patient care among cancer and treatments suffering. Opioids are one of the most important treatments in the management of dyspnoea and pain. Every new drug in supportive care is tested to diminish side effects of treatment like erythropoietin against anemia or aprepitant against emesis. Many trials are developed to enhance this supportive care especially in lung cancer management.

Targeted molecular therapies, mainly enzyme inhibitors and humanized antibodies, are being widely developed, especially in the area of lung cancer. Though often considered to be better tolerated than conventional cytotoxic chemotherapies, targeted molecular therapies induce specific toxicities that may have detrimental effects on the quality of life. We sum up various toxicities from targeted treatment available for lung cancer in France with the aim of improving their prevention, diagnosis and management.

Nutritional status assessment during the comprehensive management of patients treated for cancer is becoming increasingly necessary. Various data are currently available which show a relationship between the nutritional status and certain morbidity-mortality parameters. In contrast, there is a paucity of data concerning lung cancer. A relationship between survival and the nutritional status has been found in the literature, exclusively in advanced stages of lung cancer. Unlike that observed in oncological digestive tract surgery, where artificial nutrition is recommended preoperatively in severely malnourished patients, no link has been evidenced between postoperative morbidity and mortality and the preoperative nutritional status in lung surgery. The scientific nutritional societies simply recommend preoperative nutritional assessment. Reflection on management of malnourished patients receiving chemotherapy is still "archaic" and recent studies and recommendations are lacking. Although largely prescribed, oral nutritional supplements have not proven efficient and patient compliance will probably have to be improved. According to "good nutrition practice" rules, the digestive tube should be used when it is functional and in theory, enteral nutrition is indicated in this situation. In addition to the lack of clinical studies, one of the obstacles to its use is cultural with the need to obtain not only patient approval but also that of the prescriber. Parenteral nutrition was discredited in earlier studies. It should probably be reevaluated in the context of new chemotherapeutic molecules and a different way of handling nutrition care. The physiological concept of omega-3 fatty acid modulation of inflammation is of interest in animal studies but the clinical modalities of use remain to be defined and determined. The role of nutrition in the management of lung cancer is still very limited but there are major expectations and many solutions are awaited in the coming years.

This relation is sometimes described as a double association: venous thromboembolism (VTE) can reveal cancer (so-called Trousseau syndrome), but cancer and its treatment are also risk factors for VTE. Lung cancer, frequent and serious, is one of the greatest purveyors of VTE, a disease that pneumologists and oncologists must often confront in diagnosis, prevention, and treatment. This article investigates the epidemiological, prevention, and treatment aspects of VTE in cancer patients, particularly those with lung cancer, but also discusses diagnostic specificities and, briefly, the possible antitumor effect of heparins.

Erythopoietin (EPO) treatment of anemia during cancer has dramatically improved the tolerance of chemotherapy and quality of life of patients at all stages of the disease. Several surveys have demonstrated a high prevalence and a high incidence of anemia in lung cancer patients. The guidelines updates concerning EPO treatment for these patients are described. They take into account the debate concerning the potential harm of these molecules on the neoplastic disease and the possible role of EPO receptors expressed by several tumors, including non small cell lung cancer.

Nausea and vomiting are frequent symptoms that deteriorate the quality of life of lung cancer patients. They are most often iatrogenic and related to chemotherapy based on platinum salts; they can also be evidence of metastasis to the brain or hypercalcemia. Understanding the physiopathological mechanisms at work can make it possible to adopt effective therapeutic measures that are specific to each etiological context.

Damage to the central nervous system induced by treatment of brain tumors is common and impairs the patient quality-of-life. Neurotoxicity is induced by synergistic effects of different cytotoxic treatments such as radiotherapy and chemotherapies administered concurrently or sequentially. Recent progress in the management of brain tumors has led to new neurotoxicities. The growing concern about the neuropsychological performance of patients has disclosed another type of brain damage which has been largely neglected to date. Neurological toxicity can be acute, requiring dose adaptation or a change of drugs. But it also often occurs late and can be irreversible. To date, treatments have been ineffective. The early diagnosis of neurotoxicity is thus a major challenge. Numerous clinical studies suggest an individual sensitivity which is not only related to age or vascular status, but also to genetic predisposition that remains to be detailed. Understanding the mechanisms of personal susceptibilities would be helpful in designing more tailored treatments. In this review we address the question of adverse effects of brain radiation as well as those of chemotherapy protocols which are particularly toxic for the central nervous system that is, methotrexate, platin and aracytin.

Hemolytic uremic syndrome (HUS) in children is classically associated with diarrheas related to the production of a shiga-toxin. HUS occurs among oncologic patients, in relation with the cancer itself, or as a complication of the cytostatic treatment. The physician should be familiar with the triad of HUS (microangiopathic hemolytic anemia, thrombocytopenia and renal failure) and search actively for this pathology in oncologic patient. The treatment is essentially empirical. It includes plasma exchanges, control of blood pressure, hydro-electrolytic balance control with dialysis, if necessary. Blood transfusion should be avoided. Potential mortal complications associated with HUS can be prevented by a rapid diagnosis and a prompt initiation of adequate therapy.

Drug-induced enterocolitis is a frequent but underdiagnosed disease. Gross and microscopic features are often non-specific, except for particular cases. Drug-induced enterocolitis is usually a diagnosis of exclusion. In this article we describe the pathologic features and causes of various cases of drug-induced enterocolitis.

A case of a menopausal woman known for a chronic diffuse pain syndrome and breast cancer positive for estrogen receptors is presented. She developed an increase of her diffuse pain syndrome and joint aches after the introduction of an aromatase inhibitor. Soreness quickly improved after the interruption of the drug. We emphasize some etiological hypotheses concerning the painful symptoms, especially the role of aromatase and estrogens.

Mifepristone, a progesterone receptor antagonist steroid, can reduce uterine fibroid tumours' growth by several pathways. Its efficiency has been widely evaluated in symptomatic patients for more than 10 years. A significant decrease in fibroid tumours and uterine volume concomitant with better quality of life scores can be obtained with a daily administration of Mifepristone 5mg. Mifepristone can be compared with GnRH agonists in terms of efficiency. Observed adverse outcomes are hot flushes (38%), elevated hepatic enzymes (4%) and benign endometrial hyperplasia (28%). Hot flushes and endometrial hyperplasia are not observed with 5mg daily doses. Data suggest that many invasive procedures could be avoided with the routine use of Mifepristone for fibroid tumours care. However, published study periods are only three to 12 months: long lasting evaluation in larger groups of patients seems necessary before this treatment could be proposed as routine care.