[Targeted agents in the treatment of lung cancer]. / Place des traitements ciblés dans la prise en charge des cancers broncho-pulmonaires.

Lung cancer is in France, the leading cause of cancer death. Despite the dramatic advances that have allowed in a few years to go, for metastatic cancer, from a median survival without specific treatment of 4.5 months and now almost always more than one year, survival remains disappointing and further improvements are needed. Progress in the accumulated knowledge of the inner workings of normal and tumoral cells have paved the way for the development of targeted therapeutics called biological or simply targeted therapies. Two biological processes are already the target of marketed drugs, this is the way the receptor of epidermal growth factor (EGFR) and the path of neo-angiogenesis. It is almost assumed that, in the very near future, the inhibition of EML4-ALK will also be the subject of new drugs. In the medium term, it is conceivable that the molecular dissection of the tumors actually lead to the prescription of treatments tailored to mutations and other abnormalities that direct the growth of cancers.

Mycophenolate mofetil in patients with systemic lupus erythematosus: a prospective pharmacokinetic study.

Few studies have assessed the pharmacokinetics of mycophenolic acid (MPA) in non-transplanted patients treated with mycophenolate mofetil (MMF), and little information is available concerning a concentration-effect relationship between the MPA area under the curve (AUC) and the immunological parameters in patients treated for systemic lupus erythematosus (SLE). We evaluated the variations in pharmacokinetics for MPA in patients with SLE and the relationship between MPA-AUC and markers of disease activity. MPA blood concentrations were measured through enzyme-multiplied immunotechnique (T(0), T(30'), T(1h), T(2h), T(3h) and T(4h)) to determine the MPA AUC(0-4h) in patients treated with MMF since at least 4 weeks for SLE. Clinical examination, biochemical analyses and immunological analyses were performed on the same day. The relationship between MPA exposure and disease activity markers was assessed. A total of 20 patients were included in the study. The diagnosis of SLE had been made 87 +/- 72 months before and patients had been treated with MMF for 31 +/- 30 months. Mean dose of MMF on the day of the study was 1600 +/- 447 mg/day. Mean MPA AUC(0-4h) was 28.4 +/- 13.6 mg h/L, mean dose-normalised AUC(0-4h) was 35.5 +/- 13.8 mg h/L and mean MPA C(0) was 3.1 +/- 2.2 mg/L. There was a high correlation between MPA AUC(0-4h) and MPA C(0), (r = 0.80; P < 0.001). AUC(0-4h) tended to be lower in patients who had low complement C3 concentration (<0.67 g/L) and low complement C4 concentration (<0.14 g/L). Moreover, there was a significant relationship between MPA trough levels and complement C4 concentrations (P = 0.043). We confirmed high inter-individual variability of MPA AUC in patients treated with MMF for SLE. This suggests that MPA exposure may be unpredictable with a fixed MMF dose. There was a concentration-effect relationship between MPA exposure (C(0)) and immunological disease activity parameters.