Benoit You

Claude Bernard University Lyon 1, Villeurbanne, Rhône-Alpes, France

Are you Benoit You?

Claim your profile

Publications (76)302.39 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Intraperitoneal (IP) vascular endothelial growth factor (VEGF) levels have been shown to vary in the peritoneal cavity of patients with peritoneal surface malignancies. Our purpose was to correlate levels of IP VEGF with overall and disease-free survival to identify whether IP VEGF can be used to prognosticate patients and the possible role of IP bevacizumab. From February to October 2012, 97 consecutive patients with peritoneal carcinomatosis were treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Intravenous (IV) VEGF levels were taken before surgery, whereas IP VEGF levels were taken at various time points during and after surgery. Median follow-up was 19.48 months. On univariate analysis, a lower IP VEGF taken just after incision (T1) was associated with improved overall (P = 0.0004) and disease-free survival (P = 0.0006) at 2 years. A lower T1/IV VEGF ratio also was associated with improved overall (P = 0.004) and disease-free survival (P = 0.0051). On multivariate analysis, a lower T1 was associated with improved overall survival, whereas a lower T1/IV VEGF was associated with improved disease-free survival. On subset analysis, these two variables were associated with improved survival in colorectal cancers. A lower IP VEGF level prior to surgery is associated with improved survival. The use of preoperative intraperitoneal bevacizumab for patients with a heavy disease load should be considered, especially in colorectal cancers.
    Annals of Surgical Oncology 06/2015; DOI:10.1245/s10434-015-4644-7 · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT Optimal development of targeted drug combinations is one of the future challenges to be addressed. Computerization and mathematical models able to describe biological phenomena and to simulate the effects of changes in experimental conditions may help find solutions to this issue. We propose the concept of 'multiparameter trials', where biological, radiological and clinical data required for modeling purpose are collected and illustrated by the ongoing academic EVESOR trial. The objective of the model-based work would be the determination of the optimized doses and dosing schedules of everolimus and sorafenib, offering the maximization of the predicted modeled benefit/toxicity ratio in patients with solid tumors. It may embody the 'proof of concept' of model-based drug development of anticancer agent combinations.
    Future Oncology 05/2015; 11(10):1511-8. DOI:10.2217/fon.15.49 · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT Optimal development of targeted drug combinations is one of the future challenges to be addressed. Computerization and mathematical models able to describe biological phenomena and to simulate the effects of changes in experimental conditions may help find solutions to this issue. We propose the concept of 'multiparameter trials', where biological, radiological and clinical data required for modeling purpose are collected and illustrated by the ongoing academic EVESOR trial. The objective of the model-based work would be the determination of the optimized doses and dosing schedules of everolimus and sorafenib, offering the maximization of the predicted modeled benefit/toxicity ratio in patients with solid tumors. It may embody the 'proof of concept' of model-based drug development of anticancer agent combinations.
    Future Oncology 05/2015; 11(10):1511. · 2.61 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Assessment of treatment efficacy in metastatic castration-resistant prostate cancer (mCRPC) is limited by frequent nonmeasurable bone metastases. The count of circulating tumor cells (CTCs) is a promising surrogate marker that may replace the widely used prostate-specific antigen (PSA). The purpose of this study was to quantify the dynamic relationships between the longitudinal kinetics of these markers during treatment in patients with mCRPC. Data from 223 patients with mCRPC treated by chemotherapy and/or hormonotherapy were analyzed for up to 6 months of treatment. A semimechanistic model was built, combining the following several pharmacometric advanced features: (1) Kinetic-Pharmacodynamic (K-PD) compartments for treatments (chemotherapy and hormonotherapy); (2) a latent variable linking both marker kinetics; (3) modeling of CTC kinetics with a cell lifespan model; and (4) a negative binomial distribution for the CTC random sampling. Linked with survival, this model would potentially be useful for predicting treatment efficacy during drug development or for therapeutic adjustment in treated patients.
    04/2015; 4(5). DOI:10.1002/psp4.34
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: In cancer care, clinical pharmacists contribute to improving prevention and management of drug-related problems (DRPs). The 3-year EPICC study (Evaluation of Pharmaceutical Intervention in Cancer Care) aimed to collect and analyse pharmaceutical interventions (PIs) in oncology. The free online version of the French Society of Clinical Pharmacy (SFPC) coding system, ACT-IP, was used, supplemented by a standardized dedicated cancer-care decision tree. A total of 29 589 medication orders (77 004 anticancer drug preparations) were analysed. Eight hundred and ninety-four PIs were recorded. ACT-IP identified 54·1% of DRPs as concerning over- or underdosage. The standardized dedicated cancer-care decision tree identified the three principal causes of dosage problems: 50·2% due to miscalculation, 20% to omission of dose adjustment and 12% to poor choice of antineoplastic regimen. About 13·8% of DRPs were adverse effects and 3·9% were drug-drug interactions. The decision tree showed that 22% of adverse events could be circumvented by a switch within the same drug family and 72% of drug-drug interactions would have led to increased neoplastic toxicity. Pharmaceutical analysis of prescription forms contributes to medication safety in cancer care, and the present dedicated decision tree highlights additional information about DRPs and PIs. The DRP rate (3% of prescriptions) was consistent with the literature. The pharmacist has a role to play in optimizing the management of patients with cancer in terms of dose adjustment, drug toxicity management, improvement of administration and drug-drug interactions. This study, highlighting PIs in cancer care, is the first of this scale in terms of number of prescriptions analysed (nearly 30 000). Results demonstrated the specificity of DRPs and PIs for patients with cancer and the value of a dedicated coding system in cancer care. © 2015 John Wiley & Sons Ltd.
    Journal of Clinical Pharmacy and Therapeutics 01/2015; 40(2). DOI:10.1111/jcpt.12242 · 1.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Drug-drug interactions (DDIs) may occur with investigational drugs and affect patient safety, trial outcomes, and drug development. A list of preferred drugs with minimal risks of DDIs for treatment of symptoms or comorbidities frequently encountered by cancer patients would be helpful. We reviewed the literature to assess DDIs reported for the main drugs available for treatment of symptoms/comorbidities frequently encountered by cancer patients. Reviews and relevant original articles cited were retrieved and analyzed, and the following data were collected and double-checked: pharmacological properties; effects, if any, of drugs on CYP enzymes, membrane transporters, and QT interval; and involvement in significant DDIs. A list of preferred drugs with minimal risks of DDIs was compiled. Acknowledging for heterogeneity in data sources, prevention of unexpected DDIs during clinical trials may be improved by using this list of preferred drugs for the management of study patient's symptoms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Critical Reviews in Oncology/Hematology 01/2015; 94(2). DOI:10.1016/j.critrevonc.2014.12.014 · 4.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: At the end of the dose escalation step of phase I trials in oncology, it is increasingly frequent to include patients in expansion cohorts. However, the objective of the expansion cohorts, the number of patients included and their justification are insufficiently explained in the protocols. These cohorts are sometimes of considerable size. The aim of this article is to outline the methodology of expansion cohorts in order to provide recommendations for their planning in practice. This work has been undertaken in collaboration with the statisticians of the early phase investigation centers (CLIP(2)), supported by INCA. First, we have outlined the recent articles published on the expansion cohorts in phase I. We then proposed recommendations, in terms of objectives and number of patients to be included, to guide investigators and facilitate the use of these expansion cohorts in practice. Manji et al. have identified 149 phase I clinical trials using expansion cohorts in oncology with a review of the literature between 2006 and 2011 (Manji et al., 2013). Objectives of the expansion cohort were reported in 111 trials (74 %). In these trials, safety was the most reported objective (80 % of trials), followed by efficacy (45 %). According to this review, the number of patients included in these cohorts was insufficiently justified. This result was confirmed by the study of literature that we conducted over the period 2011-2014. We propose to define the number of patients to be included in expansion cohorts in terms of (1) their objectives, (2) the statistical criteria and (3) the clinical context of the trial. The toxicity study remains the primary objective to evaluate in the expansion phase. In some contexts, the activity study is considered as co-primary objective, either for identifying preliminary signs of activity in studies like screening, or for studying the activity when the target population is known. This study is then considered as phase I/II, and experience plans of phase II can be adapted for planning expansion cohorts. Recommendations for the size of expansion cohorts are proposed. Despite the exploratory character of the expansion cohort, a justification of their size based on assumptions statistically defined is recommended in order to provide an interpretable conclusion and to quantify the risk of errors. Copyright © 2014 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.
    Bulletin du cancer 01/2015; 102(1). DOI:10.1016/j.bulcan.2014.10.001 · 0.64 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Consolidated Standards of Reporting Trials (CONSORT) guidance was extended in 2013 to provide a set of specific recommendations regarding patient-reported outcomes (PROs) reporting in randomized clinical trials (RCTs). There is limited data regarding how well current publications of oncology RCTs report PROs if assessed using these guidelines.
    Annals of Oncology 10/2014; DOI:10.1093/annonc/mdu489 · 6.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: What is known and objectiveMedication errors (ME) in oncology are known to cause serious iatrogenic complications. However, MEs still occur at each step in the anticancer chemotherapy process, particularly when injections are prepared in the hospital pharmacy. This study assessed whether a ME simulation program would help prevent ME-associated iatrogenic complications.Methods The 5-month prospective study, consisting of three phases, was undertaken in the centralized pharmaceutical unit of a university hospital of Lyon, France. During the first simulation phase, 25 instruction sheets each containing one simulated error were inserted among various instruction sheets issued to blinded technicians. The second phase consisted of activity aimed at raising pharmacy technicians' awareness of risk of medication errors associated with antineoplastic drugs. The third phase consisted of re-enacting the error simulation process 3 months after the awareness campaign. The rate and severity of undetected medication errors were measured during the two simulation (first and third) phases. The potential seriousness of the ME was assessed using the NCC MERP® index.Results and discussionThe rate of undetected medication errors decreased from 12 in the first simulation phase (48%) to five in the second simulation phase (20%, P = 0∙04). The number of potential deaths due to administration of a faulty preparation decreased from three to zero. Awareness of iatrogenic risk through error simulation allowed pharmacy technicians to improve their ability to identify errors.What is new and conclusionThis study is the first demonstration of the successful application of a simulation-based learning tool for reducing errors in the preparation of injectable anticancer drugs. Such a program should form part of the continuous quality improvement of risk management strategies for cancer patients.
    Journal of Clinical Pharmacy and Therapeutics 10/2014; 40(1). DOI:10.1111/jcpt.12225 · 1.53 Impact Factor
  • 39th ESMO Congress (ESMO); 09/2014
  • Source
    Placenta 09/2014; 35(9):A51. DOI:10.1016/j.placenta.2014.06.166 · 3.29 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background Patients with advanced metastatic disease are often treated aggressively with multiple lines of chemotherapy, even in the last month of life. The benefit of such an approach remains uncertain. The objective of the study was to investigate whether Ruta graveolens 9c homeopathic medicine can improve quality of life (QoL) and tumour progression in patients with advanced cancer. Material and methods This was a single-centre, open-label, uncontrolled, pilot study. Patients (>18-years, life-expectancy ≥3 months, performance status ≤2) with locally-advanced solid tumours or metastases, previously treated with all available standard anti-cancer treatments were recruited. Oral treatment consisted of two 1-mL ampoules of Ruta graveolens (9c dilution) given daily for a minimum of 8 weeks, or until tumour and/or clinical progression. Primary outcome was QoL measured using the EORTC QLQ-C30 questionnaire. Secondary outcome measures were anxiety/depression measured using the Hospital Anxiety and Depression Scale (HADS), WHO performance status (PS), tumour progression assessed using RECIST criteria and tumour markers, survival and tolerance. Results Thirty-one patients were included (mean age: 64.3 years). Mean duration of treatment was 3.3 months (median: 2.1). QoL global health status improved significantly between baseline and week 8 (P < 0.001) and week 16 (P = 0.035), but was at the limit of significance (P = 0.057) at the end of the study. There was no significant change in anxiety/depression or PS during treatment. Ruta graveolens 9c had no obvious effect on tumour progression. Median survival was 6.7 months [95%CI: 4.8–14.9]. Ruta graveolens 9c was well-tolerated. Conclusion Some patients treated with Ruta graveolens 9c had a transitory improvement in QoL, but the effectiveness of this treatment remains to be confirmed in further studies.
    Homeopathy 07/2014; 103(4). DOI:10.1016/j.homp.2014.06.001 · 0.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Dans les tumeurs trophoblastiques gestationnelles (TTG) de bas risque, la détermination précoce du risque de résistance à la chimiothérapie de première ligne serait utile. Les stratégies fondées sur l’observation d’un point de concentration d’hCG à la première ou à la septième semaine de traitement manquent de reproductibilité. Les approches fondées sur la modélisation permettant de calculer les équations mathématiques des cinétiques individuelles d’hCG semblent prometteuses. La reproductibilité de la valeur prédictive précoce de paramètres modélisés a été démontrée dans trois larges études internationales. Il devrait être possible de définir pour chaque patiente son risque de résistance en intégrant dans un programme informatique les valeurs d’hCG mesurées durant les 50 premiers jours de traitement. Une validation prospective internationale de cette approche est prévue. Abstract Early determination of the resistance risk to firstline chemotherapy in patients with low-risk gestational trophoblastic disease would be helpful. The strategies based on one hCG time point measured during the 1st or the 7th week of treatment are not reproducible enough. Model-based approaches that enable calculation of the mathematical equations of hCG individual kinetics are promising. The reproducibility of the early predictive value of modelled kinetic parameters was shown in three large international studies. It should be possible to define for any patient her risk of resistance by integrating the hCG values measured during the first 50 treatment days in a program. An international validation of this concept is planned.
    Oncologie 06/2014; 16(6):300-305. DOI:10.1007/s10269-014-2408-9 · 0.08 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: DOSSIER Place de l'hystérectomie d'emblée dans la prise en charge des tumeurs trophoblastiques gestationnelles à bas risque Résumé Introduction : Le traitement recommandé des tumeurs trophoblastiques gestationnelles (TTG) à bas risque est une monochimiothérapie, habituellement par méthotre-xate. La place de l'hystérectomie en première intention est mal définie dans cette indication. Méthodes : Évaluation de la normalisation des hCG des TTG à bas risque après hystérectomie initiale, enregistrées par le Centre français des maladies trophoblastiques de Lyon, France, entre 1999 et 2013. Résultats : Sur les 54 patientes incluses, 43 (80 %) ont été guéries définitivement par une hystérectomie. Aucun critère d'échec n'a pu être mis en évidence de façon significative. Conclusion : Une hystérectomie est une option thérapeutique possible des TTG à bas risque en cas de demande de la patiente. Mots clés Hystérectomie · Tumeur trophoblastique gestationnelle · Môle hydatiforme Abstract Introduction: Single agent chemotherapy, most usually methotrexate, is the treatment for low-risk Gestatio-nal Trophoblastic Neoplasia (GTN). The role of hysterec-tomy is not clearly known in this situation. Methods: Complete hCG normalization after hysterectomy was evaluated in case of low-risk GTN, in the French Center for Trophoblastic Disease, Lyon, France, between 1999 and 2013. Results: Forty-three patients out of the fifty-four included (80%) were cured by hysterectomy alone. No criteria were predictive of failure. Conclusion: Hysterectomy could be an option in certain cases of low-risk GTN, especially on patient's request.
    Oncologie 06/2014; 16(6):285-90. DOI:10.1007/s10269-014-2401-3 · 0.08 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: To reduce the occurrence of medication errors, a systemic approach was developed combining anti-neoplastic medication error reviews and morbidity and mortality conferences (M&MCs). We report the first experience of implementing this strategy in oncology. Methods: The case reports submitted to combined reviews were prepared by physicians and pharmacists, and medication error(s) were described and chronological and root-cause analyses were performed. Results: Ten combined reviews were conducted, which involved the departments of haematology, medical oncology, pneumology, gastroenterology and clinical oncology pharmacy. A total of 91 errors were analysed, of which 3 had reached the patient. Thirty-four corrective actions were proposed; 53% consisted of changes in practice, 35% in procedural reminders and 12% in on-ward education sessions. Conclusions: The combination of medication error reviews and M&MCs appears to be an efficient means of improving cancer patient safety and personnel proficiency. This multidisciplinary work is indispensable to improve future patient management through the critical analysis of past medical errors. © 2014 S. Karger AG, Basel.
    Chemotherapy 04/2014; 59(5):330-337. DOI:10.1159/000358190 · 1.55 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early prediction of the expected benefit of treatment in recurrent ovarian cancer (ROC) patients may help in drug development decisions. The actual value of 50% CA-125 decrease is being reconsidered. The main objective of the present study was to quantify the links between longitudinal assessments of CA-125 kinetics and progression-free survival (PFS) in treated recurrent ovarian cancer (ROC) patients. The CALYPSO randomized phase III trial database comparing two platinum-based regimens in ROC patients was randomly split into a "learning dataset" and a "validation dataset". A parametric survival model was developed to associate longitudinal modeled CA-125 changes (ΔCA125), predictive factors, and PFS. The predictive performance of the model was evaluated with simulations. The PFS of 534 ROC patients were properly characterized by a parametric mathematical model. The modeled ΔCA125 from baseline to week 6 was a better predictor of PFS than the modeled fractional change in tumor size. Simulations confirmed the model's predictive performance. We present the first parametric survival model quantifying the relationship between PFS and longitudinal CA-125 kinetics in treated ROC patients. The model enabled calculation of the increase in ΔCA125 required to observe a predetermined benefit in PFS to compare therapeutic strategies in populations. Therefore, ΔCA125 may be a predictive marker of the expected gain in PFS and an early predictive tool in drug development decisions.
    Gynecologic Oncology 04/2014; DOI:10.1016/j.ygyno.2014.04.003 · 3.69 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The primary objective of this study was to determine the incidence rate of pathological complete responses (pCRs) following neoadjuvant systemic chemotherapy for the treatment of peritoneal carcinomatosis (PC) of colorectal origin. The secondary objective was to evaluate whether pathological response assessments predict survival of patients treated with curative intent by complete cytoreductive surgery (CRS). A retrospective review was performed of 115 patients who underwent preoperative irinotecan- or oxaliplatin-based chemotherapy, followed by 124 procedures of complete CRS alone or combined with hyperthermic intraperitoneal chemotherapy (HIPEC). The pathological response was defined as the mean percentage of cancer cells remaining within all specimens. Univariate and multivariate analyses were performed to identify predictors of survival and pathological response outcome. Twelve procedures (9.7 %) resulted in pCRs, defined as no residual cancer cells in all specimens, 25 (20.2 %) resulted in major responses (1 to 49 % residual cancer cells), and 87 (70.1 %) resulted in minor or no responses (>50 % residual cancer cells). The cumulative 5-year survival rates were 75 and 57 % for patients with pCR and major responses, respectively. Using multivariate analysis, pathological response was the only independent predictor of survival (P = 0.01; major response: hazard ratio [HR] = 4.91; minor response: HR = 13.46). No significant predictor of pathological response was identified. Pathological complete response can be achieved with preoperative systemic chemotherapy for patients with PC of colorectal origin. The degree of pathological response can be assessed and represented as a new outcome for prognosis following treatment with curative intent.
    Annals of Surgical Oncology 03/2014; 21(8). DOI:10.1245/s10434-014-3647-0 · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Even though anticancer drugs are prepared in dedicated pharmaceutical units, nurses remain exposed to cytotoxic agents during administration to patients. Objective The aim of this study was to assess this occupational exposure during the intravenous line–purging procedure at the patient’s bedside before administration in oncology departments. Methods This prospective study was conducted over a 4-week period in the hematology and oncology departments at a university hospital. Amounts of doxorubicin and cyclophosphamide on the surface of nurses’ gloves were measured after the intravenous line purge of the infusion bag and the connection to the patient. For this purpose, gloves were washed with sterile water, following a validated procedure. Quantification of the 2 drugs into the water was performed using LC-MS/MS. Results After 59 chemotherapy administrations, 30.5% of gloves were contaminated. Despite extremely low volumes of contamination (0.08–6.28 µL), amounts collected ranged from 190 to 2500 ng per pair of gloves that tested positive for doxorubicin (median, 1600 ng) and from 130 to 32,600 ng with cyclophosphamide (median, 2700 ng). Conclusions The intravenous line purge preceding antineoplastic infusion bag administration is a potential source of contamination in nurses. Contaminations appear to be invisible but frequent (in >30% of cases). Therefore, intravenous line purging performed under appropriately safe conditions should be mandated in pharmaceutical units dedicated to injectable-drug preparation. This measure should be included as a standard hospital practice as a matter of urgency.
    Clinical Therapeutics 03/2014; 36(3). DOI:10.1016/j.clinthera.2014.01.016 · 2.59 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: The main objective of the present study was to establish the relationships between CA-125 kinetics and tumour size changes during treatment. Methods: The data from the CALYPSO-randomised phase III trial, comparing two platinum-based regimens in recurrent ovarian cancer (ROC) patients, was randomly split into a ‘learning data set' to estimate model parameters and a ‘validation data set' to validate model performances. A kinetic–pharmacodynamic semi-mechanistic model was built to describe tumour size and CA-125 kinetics during chemotherapy. The ability of the model to predict tumour response induced by chemotherapy, based on CA-125 values, was assessed. Results: Data from 535 ROC patients were used to model CA-125 kinetics and tumour size changes during the first 513 days after treatment initiation. Using the validated model, we could predict with accuracy the tumour size changes induced by chemotherapy based on the baseline imaging assessment and longitudinal CA-125 values (mean prediction error: 0.3%, mean absolute prediction error: 10.6%). Conclusions: Using a semi-mechanistic model, the dynamic relationships between tumour size changes and CA-125 kinetics induced by chemotherapy were established in ROC patients. A modelling approach allowed CA-125 to be assessed as a biomarker for tumour size dynamics, to predict treatment efficacy for research and clinical purposes.
    British Journal of Cancer 02/2014; 110(6). DOI:10.1038/bjc.2014.75 · 4.82 Impact Factor

Publication Stats

376 Citations
302.39 Total Impact Points

Institutions

  • 2007–2015
    • Claude Bernard University Lyon 1
      • Equipe de recherche en ciblage thérapeutique en oncologie
      Villeurbanne, Rhône-Alpes, France
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2008–2014
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2007–2014
    • Centre Hospitalier Lyon Sud
      Lyons, Rhône-Alpes, France
  • 2012
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2011
    • University of Toronto
      Toronto, Ontario, Canada
  • 2010–2011
    • University Health Network
      Toronto, Ontario, Canada