Background Malignant gliomas (MG) comprise the most common types of primary central nervous system tumours. Purpose An observational study to evaluate the efficacy and safety of bevacizumab plus irinotecan used off-label in recurrent malignant gliomas. Materials and Methods Pharmacy records were reviewed to identify patients with histologically proven MG who had been treated with bevacizumab plus irinotecan as second-or third-line chemotherapy. Eligible patients: radiological evidence of tumour recurrence or progression prior to initiation of chemotherapy and STUPP regimen as first line. Patients were treated with IV bevacizumab (10 mg/kg) on days 1, 15 and 29 every 6 weeks and IV irinotecan (340 mg/m² if concomitant enzyme-inducing antiepileptic drugs (EIAEDs) or 125 mg/m 2 if no EIAEDs) on days 1, 15 and 29 every 6 weeks. Treatment was continued until disease progression or unacceptable toxicity. Tumours were evaluated by brain MRIs. Response to treatment was assessed at baseline and every 3 cycles or whenever progression was clinically suspected. The Macdonald criteria were used to evaluate the response. Toxicity was assessed before each cycle by medical history, haematology and biochemistry. Adverse events were graded according to NCI-CTCAEv4. Antiepileptics were administered as medically indicated. Results Seven patients (5 men, 2 women) were evaluated. Mean age was 52.4 years and glioblastoma multiforme (GBM) was the major histotype (71%). 71.4% of patients had had a total resection as primary surgery and 14.3% of patients had undergone second surgery at disease recurrence. The median number of cycles administered was 4. Overall activity comprised 3 partial responses (42.86%); and 1 (14.28%) disease stabilisation for a Disease Control Rate of 57.14%. Three patients (42.86%) experienced disease progression. The median progression-free survival was 8.2 months (95% confidence interval (CI): 5.4-10.9) and the median overall survival was 11.8 months (95% CI: 6.1-17.5). No central nervous system haemorrhages occurred, but one patient developed deep venous thromboses. Conclusions The combination of bevacizumab and irinotecan seems to run as an alternative and active regimen for recurrent MG with acceptable toxicity but it is necessary to expand the study population to draw definitive conclusions. No conflict of interest. Budget imPact analysis on new 3-year imatiniB adjuvant treatment For Patients with oPeraBle gist at high risk oF recurrence

Background Good Clinical Practice specifies the role of the pharmacist in clinical trials. For each prescription dispensed for a named patient, the pharmacist is responsible for educating the patient on the treatment, counting any residual Investigational Medicinal Product (IMP), and thus for evaluating the compliance. Purpose To assess the importance of pharmaceutical vigilance about IMPs. Materials and Methods This prospective study took three months. For each named-patient prescription dispensed, a count of returned treatment (RT) by the patient from the previously dispensed medicines was performed to assess compliance. Results 117 RTs were analysed. 43 additional RTs from 1 clinical trial were not included in this study due to the impossibility of evaluating compliance (posology changes not notified to the pharmacy and unsuitable secondary packaging). The non-conformity rate was 20% (23 RT). 39% (n = 9) of the non conformities (NC) were due to allowing empty boxes not to be returned. In 61% (n = 14) of NC there was a discrepancy between the expected count of returned IMPs and the one actually made, showing poor compliance.Average counting time was 12 minutes (5-30 min). An exact count of returned IMP was operated during dispensing for 34% of returns and after dispensing for 66%. In all cases, a global analysis was performed before the prescription was dispensed. Conclusions This study points out the major role of the pharmacist in the education of the patient enrolled in clinical trials, about the return of all experimental medicines and the therapeutic schedule. It appeared very important to evaluate compliance while the pharmacist was dispensing the next prescription, independently of the time consumed, in order to correct possible errors in taking the medicines at that time.No conflict of interest. IncIdence and causes of capecItabIne dose adjustment In colon cancer patIents

Background The purpose of labelling is to protect persons who take part to biomedical research. It must enable the product and study to be identified and the drugs to be used safely. The decree of 24 May 2006 [1] sets out the information to be included on the labelling of investigational medical product (IMPs). Purpose To evaluate the regulatory conformity of the labelling of IMPs. Materials and Methods An assessment grid was established from the decree of 24 May 2006. This audit investigated the labelling of the primary or secondary packaging, according to the presentation, of 135 IMPs corresponding to 75 clinical trials. Results Of 135 labels analysed, only 11 (8.1%) bore all the information required by the legislation. On 3 labels, information didn’t appear in French. In more than 5% of the cases, information allowing identification of the product and the study and the good use of the drugs was absent from label. In other cases the following was missing: pharmaceutical form (15.4%), route of administration (15.3%), content of the active substance (11.6%), product identification (6.88%), clinical trial reference (6.88%), patient visit number (71.9%) and storage conditions (14.4%). 57.8% of the labels came in layers. Basic information was not present on the first layer in 26.1% of the cases for the pharmaceutical form, route of administration (55.9%), dosage (13.8%), product identification (11.7%) or storage conditions (45.8%). Conclusions In spite of important and rigorous regulation, we noted non-conformities in labelling with sometimes important omissions. The significant number of statements required to appear on the label leads sponsors to reduce font size and to present the labels in layers. This audit highlights that the significant amount of information on the label makes it difficult to read and can lead to medicines errors, especially in elderly patients. Reference Order of 24 May 2006 establishing the content for the labelling of investigational medicinal products published in France’s official journal on 30 May 2006. No conflict of interest.

Background Around 3000 batches of medicinal products are prepared each year in Lapeyronie Hospital.For each batch, a batch file (BF) is created. This contains the prescription, a manufacturing and labelling sheet (MLS) and a control and batch release sheet (CBRS). Purpose Since the publication of the French Good Manufacturing Practice in 2007, a process of quality improvement has been implemented. An internal audit of all 2011 BFs has been conducted to evaluate the non-conformity (NC) rate. Materials and Methods An internal control questionnaire (ICQ) evaluating various criteria was written by the pharmacist and completed by students and residents for each BF. The results were compared with a previous 2010 study. Results 42% of 2,858 BFs were not acceptable. There were 1691 non-conformities (a BF can be unacceptable on several criteria): 32% of the unacceptable BFs had a problem with the prescription, 59% had inaccuracies with the MLS and 9% with the CBRS.Of those with prescription problems, pharmaceutical validation traceability was lacking for 49% and 31% had not been signed by the MD.The absence of checking the sheet before preparation was the major NC factor (79%) regarding the MLS. The volume of raw materials was not checked during preparation in 8.6% of MLS.NC regarding CBRS was due to incomplete checking of the preparation before it was released (36%).Results in these 2 studies showed that the MLS was not checked before preparation in 28% of BFs in 2011 against 71% in 2010. The volume cheque before preparation was not performed in 41% of BF in 2011 against 85% in 2010. Conclusions Following this audit, corrective actions were instituted: pharmacists were trained on the importance of the pharmaceutical validation of prescriptions, and the assistants were reminded of the importance of getting their work checked before and during preparation.Nevertheless, there has been progress in the conformity rate between these two audits, pointing out the impact of corrective actions.No conflict of interest. Background The growing use of supplementary products (herbal remedies, food supplements, etc.) poses an unignorable and poorly explored risk to hospital patients. The results of our previous study [1] show that 85.5% of hospital patients took at least one supplementary product; and with one patient out of four we have identified potential interactions. However, several questions arise about their clinical relevance: (1) Might the interaction harm the patient? ContradiCtions in the interPretation

Background The sponsor is the person or entity that initiates a clinical trial, manages it and provides funding. We define two types of promoters, commercial sponsors and academic sponsors (mainly hospitals). In order to minimise the cost of academic studies without limiting the quality, some work done by the hospital is not included, for example pharmaceutical management by pharmacies. Purpose To measure the size of pharmacy involvement in the management of clinical studies and academic costs not taken into account. Materials and Methods We accounted for all pharmaceutical work done for academic studies (dispensing, preparation, reception of goods or materials, destruction of goods or materials, monitoring, labelling, ordering, randomization) managed by our pharmacy during the year 2011. We estimated the average time for each of these duties and the resulting financial cost (national grid, LEEM). Results35 institutional studies were in progress during this period and represented approximately 20% of all studies managed by our service: 8 studies were promoted by Montpellier hospitals, 7 by associations and 20 by other hospitals. We noted 501 prescriptions dispensed, 180 assignments to treatment or randomization, 52 preparations, 138 receptions, 13 destruction, 55 orders, 416 labels prepared and 52 monitoring visits. All this took 736.5 hours (or 210 half days) and additional costs estimated at 45,752 euros. Only 8,865 euros were allocated to the pharmacy (19% of the costs). Conclusions Academic research is essential and necessary for the improvement of scientific knowledge. However, in most cases, no expenditure is planned for the pharmacy unit. Currently, these activities are made within the hospital pharmacist’s “free time”. A national reflection is currently under way to establish a grid indicating how much academic studies should pay for the recruitment of dedicated medical staff. This study demonstrates that academic research requires a considerable time from the pharmacies, to justify the allocation of human resources in order to support good management. No conflict of interest.