Single-arm phase II trial to evaluate efficacy and tolerance of regorafenib monotherapy in patients over 70 with previously treated metastatic colorectal adenocarcinoma FFCD 1404 - REGOLD.

BACKGROUND: Regorafenib significantly increases overall survival (OS) in patients with metastatic colorectal cancer previously treated but gives toxicities. OBJECTIVES: to assess the efficacy and safety of regorafenib at it's approved dose in the older population. PATIENTS AND METHODS: This multicenter single-arm phase II enrolled patients ≥70 years old after the failure of fluoropyrimidine-based chemotherapy, anti-VEGF, and anti-EGFR treatment. The primary endpoint was disease control rate (DCR) 2 months after initiation of regorafenib (160 mg/day, 3 weeks on/1 week off). RESULTS: Forty-three patients were enrolled, with a median age of 77 years. The 2 months DCR was 31.4% in the 35 evaluable patients. For the 42 patients that received at least one dose of regorafenib, median progression-free survival and OS were 2.2 and 7.5 months. The median time to autonomy degradation and quality of life degradation was 3.1 and 3.2 months, respectively. A grade 3-4 treatment-related adverse events was observed in 35/42 patients, notably: fatigue (45.2%), hand-foot skin reaction (19.0%), hypertension (21.4%), and diarrhea (7.1%). There is a trend to achieve DCR in patients ≤80 years and a trend to discontinue the study due to toxicity in patients with ECOG ≥1, over 80 years and with impaired baseline autonomy. CONCLUSION: Treatment with regorafenib in pretreated patients ≥70 years is feasible and demonstrate similar efficacy that was observed in previous studies in young patients. Fatigue is the most frequent severe adverse event. However, caution should be taken for older patients with ECOG ≥1, over 80 years, and with impaired baseline autonomy.

Determination of water quality standards for chemical mixtures: extension of a methodology developed for herbicides to a group of insecticides and a group of pharmaceuticals.

Monitoring surveys throughout America and Europe have demonstrated the widespread presence of organic synthetic substances such as pesticides and pharmaceuticals in surface water. To avoid deleterious effects on the aquatic system, many countries determine water quality criteria for pesticides. For each substance, the comparison of the concentration measured in water with its criterion gives an indication of the pressure this substance put on the aquatic system. However, in the environment, aquatic organisms are not only exposed to single pesticides but typically to mixtures of these substances. It is therefore of particular importance to take mixtures into account when defining water quality criteria, which is rarely done yet. We recently developed a method to define consistent and comparable water quality criteria for mixtures of herbicides having a similar mode of action. These criteria are calculated based on species sensitivity curves; the method assumes that these curves are parallel for substances having similar mode of action. The aim of this study was to apply our method to six organophosphates (insecticides) and to three ß-blockers (pharmaceuticals), other groups of compounds commonly detected in surface water. We found some evidence that the developed methodology gives consistent results for these groups too. The hypothesis of parallelism was accepted in 2/3 (ß-blockers) and 2/6 of the cases (organophosphates) for both species sensitivity curves based on effect concentrations 50% and on no-observed effect concentrations. The use of water quality criteria for mixture is illustrated by two case studies, which show the importance of taking mixtures into account in water quality legislation.

[EBV-induced fulminant hepatic failure: favorable outcome after liver transplantation]. / Hépatite fulminante à virus Epstein-Barr: évolution favorable après transplantation hépatique.

Viral hepatitis are the leading cause of fulminant hepatitis. Epstein Barr virus is the viral agent involved in infectious mononucleosis, associated with a frequent and usually benign hepatitis, except in case of immunodeficiency, congenital or acquired. We report the case of an immunocompetent young woman who presented an EBV induced fulminant hepatic failure, requiring liver transplantation that was successful. This observation emphasizes that EBV must be known as a possible cause of fulminant hepatitis and that liver transplantation is probably the unique therapeutic option to avoid a usually fatal course.