Benoit You

University of Lyon, Lyons, Rhône-Alpes, France

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Publications (88)332.87 Total impact

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    ABSTRACT: Patients with 2000 FIGO low-risk gestational trophoblastic neoplasia are commonly treated with single-agent chemotherapy. Methotrexate is widely used in this indication in Europe. Analysis of relapse after treatment and identification of factors associated with relapse would help understand their potential impacts on 2000 FIGO score evolution and chemotherapy management of gestational trophoblastic neoplasia patients.
    No preview · Article · Jan 2016 · American journal of obstetrics and gynecology
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    ABSTRACT: Background Peritoneal carcinomatosis is an increasingly common finding in gastric carcinoma. Previously, patients were treated as terminal, and median survival was poor. The use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in this context is still highly debatable. Objective The aim of this study was to evaluate the long-term outcomes associated with CRS and HIPEC, and define prognostic factors for cure, if possible. Patients and Methods All patients with gastric carcinomatosis from five French institutions who underwent combined complete CRS and HIPEC and had a minimum follow-up of 5 years were included in this study. Cure was defined as a disease-free interval of more than 5 years from the last treatment until the last follow-up. Results Of the 81 patients who underwent CRS and HIPEC from 1989 to 2009, 59 had a completeness of cytoreduction score (CCS) of 0 (complete macroscopic resection), and the median Peritoneal Cancer Index (PCI) score was 6. Mitomycin C was the most commonly used drug during HIPEC (88 %). The 5-year overall survival (OS) rate was 18 %, with nine patients still disease-free at 5 years, for a cure rate of 11 %. All ‘cured’ patients had a PCI score below 7 and a CCS of 0. Factors associated with improved OS on multivariate analysis were synchronous resection (p = 0.02), a lower PCI score (p = 0.12), and the CCS (p = 0.09). Conclusion The cure rate of 11 % for patients with gastric carcinomatosis who are deemed terminal emphasizes that CRS and HIPEC should be considered in highly selected patients (low disease extent and complete CRS).
    No preview · Article · Jan 2016 · Annals of Surgical Oncology
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    ABSTRACT: Background: Randomised controlled trials (RCTs) represent a major source of information on treatment-related adverse events (AEs). In this study, we reviewed the use and the reporting methods of aggregated-AEs (A-AEs) outcomes in RCTs reports published in oncology and compared that to the expectations of European Organisation for Research and Treatment of Cancer (EORTC) membership. Methods: RCTs reports published between 2007 and 2011 were reviewed regarding the reporting of A-AEs-outcomes. A-AEs were defined as summary outcome combining several related AEs, usually grouped by organ system e.g. cardiac-AEs, dermatologic-AEs. Trial characteristics associated with the use of A-AEs outcomes were investigated. The expectation of EORTC members concerning A-AEs utilisation was queried through a survey. Results: Among 325 RCTs published between 2007 and 2011, 94 (29%) included one or more A-AE outcomes. A clear description of the nature of AEs included in such aggregations was provided in 19 articles (20%). No description of A-AEs was conversely provided in the other 75 articles (80%). The most commonly used A-AEs-outcomes were dermatologic-AEs (45%) and cardiac-AEs (33%). In multivariate analysis, the use of A-AEs outcomes was more frequent when trials were conducted in Europe (p = 0.038) and in trials performed on colon/rectal cancers (p = 0.016). Finally, there is no consensus of EORTC members regarding the utilisation of A-AEs but a majority of them (88%) felt that a clear description of A-AEs should systematically be reported. Conclusions: The use of A-AEs is infrequent in oncology RCT manuscripts although their use is accepted by most clinicians. However, a clear definition of A-AEs is strongly recommended if they are to be used in order to avoid a loss of important details about drug toxicities that is useful to clinicians.
    No preview · Article · Jan 2016 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: Background: Tools for differentiating aggressive and indolent prostate carcinoma (PCa) are needed. Mathematical modeling is a promising approach for longitudinal analysis of tumor marker kinetics. Patients and methods: The prostate-specific antigen (PSA) increases from patients with PCa and those with benign prostatic hyperplasia (BPH) were retrospectively analyzed using a mathematical model. Using the NONMEM program, individual PSA kinetics were fit to the following equation: [d(PSA)/dt = (PROD.K × exp [RHO1 × t]) × (1 - BPH) + PROD.NK × exp (RHO2 × t) - KELIM × (PSA)], where RHO1 is the PSA production increase rate by PCa cells (PROD.K), RHO2 is the PSA production increase rate by non-PCa cells (PROD.NK), and KELIM is the PSA elimination rate. The comparative value of the modeled kinetic parameters, estimated for each patient, for predicting the D'Amico score and relapse-free survival (RFS) were tested using logistic regression analysis and multivariate survival tests. Results: The PSA kinetics from 62 patients with BPH and 149 patients with PCa before radical prostatectomy were successfully modeled. We identified statistically significant relationships between the PSA growth rate related to cancer cells (RHO1) and the probability of D'Amico high-risk group (less than the median RHO1 vs. at the median or greater: odds ratio, 2.15; 95% confidence interval [CI], 1.00-4.77; P = .05). RHO1 was also a significant prognostic factor for RFS on univariate analysis and against other reported prognostic factors using multivariate Cox tests. Three independent prognostic factors of RFS were found: RHO1 (hazard ratio [HR], 2.71; 95% CI, 1.25-5.84; P = .01), Gleason score (HR, 8.54; 95% CI, 4.19-17.40; P < .01), and positive surgical margins (HR, 2.04; 95% CI, 1.05-3.97; P = .03). Conclusion: Using a few PSA time points analyzed with a mathematical model (easily manageable in routine practice), it could be possible to determine before surgery whether a patient has presented with aggressive PCa.
    No preview · Article · Dec 2015 · Clinical Genitourinary Cancer
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    ABSTRACT: Objectives: In low-risk gestational trophoblastic neoplasia, chemotherapy effect is monitored and adjusted with serum human chorionic gonadotrophin (hCG) levels. Mathematical modeling of hCG kinetics may allow prediction of methotrexate (MTX) resistance, with production parameter "hCGres." This approach was evaluated using the GOG-174 (NRG Oncology/Gynecologic Oncology Group-174) trial database, in which weekly MTX (arm 1) was compared with dactinomycin (arm 2). Methods: Database (210 patients, including 78 with resistance) was split into 2 sets. A 126-patient training set was initially used to estimate model parameters. Patient hCG kinetics from days 7 to 45 were fit to: [hCG(time)] = hCG7 * exp(-k * time) + hCGres, where hCGres is residual hCG tumor production, hCG7 is the initial hCG level, and k is the elimination rate constant. Receiver operating characteristic (ROC) analyses defined putative hCGRes predictor of resistance. An 84-patient test set was used to assess prediction validity. Results: The hCGres was predictive of outcome in both arms, with no impact of treatment arm on unexplained variability of kinetic parameter estimates. The best hCGres cutoffs to discriminate resistant versus sensitive patients were 7.7 and 74.0 IU/L in arms 1 and 2, respectively. By combining them, 2 predictive groups were defined (ROC area under the curve, 0.82; sensitivity, 93.8%; specificity, 70.5%). The predictive value of hCGres-based groups regarding resistance was reproducible in test set (ROC area under the curve, 0.81; sensitivity, 88.9%; specificity, 73.1%). Both hCGres and treatment arm were associated with resistance by logistic regression analysis. Conclusions: The early predictive value of the modeled kinetic parameter hCGres regarding resistance seems promising in the GOG-174 study. This is the second positive evaluation of this approach. Prospective validation is warranted.
    No preview · Article · Nov 2015 · International Journal of Gynecological Cancer
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    ABSTRACT: Background: Determination of drug safety and tolerability is usually based on the frequency of certain key adverse events (AEs) rather than the frequency of all-grade toxicities. We assessed the reporting of key AEs in oncology randomized controlled trials (RCTs) and compared that to the expectations of the EORTC membership. Materials and methods: RCTs reports published between 2007 and 2011 were reviewed regarding the reporting of key AEs, namely: grade 3/4 AEs; grade 5 AEs; and AEs resulting in study withdrawal or in dose reduction. Study characteristics associated with better reporting of key AEs were investigated. Finally, a survey was conducted among the EORTC membership to determine their expectations on key AEs reporting. Results: Although the frequency of grade 3/4 was reported in most reports (96%), only 17% of them described the reporting threshold above which grade 3/4 AEs were included for reporting, raising the possibility that important but less frequent grade 3/4 AEs might be under-reported. Grade 5 AEs frequency and nature were adequately reported in 161 (50%) of manuscripts; AEs leading to study withdrawal in 61 manuscripts (19%); and AEs leading to dose reduction in 43 manuscripts (13%). In contrast most EORTC members expected a comprehensive reporting of grade 5 AEs (96% of EORTC member's responses), AEs leading to study withdrawal (86%) and AEs leading to dose reduction (70%). In multivariate analysis, grade 5 AEs frequencies were less frequently reported in European trials (p=0.004). Frequencies of AEs leading to withdrawals were more frequently reported in trials funded by industry (p=0.005) and in trials including patients with breast or urological cancers (p=0.006). Conclusions: These findings suggest that current practice of key AEs reporting remains highly variable and sometimes inadequate in oncology RCTs reports. Current standards for safety reporting in RCTs should be revised to highlight the importance of key AEs reporting.
    No preview · Article · Oct 2015 · Annals of Oncology
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    ABSTRACT: Background: Gestational trophoblastic diseases include premalignant (partial and complete hydatidiform moles) and malignant entities referred to as gestational trophoblastic neoplasia (GTN). Use of the FIGO prognostic score is encouraged in cases of GTN to predict the potential for developing resistance to single-agent chemotherapy. A FIGO score of 7 or higher defines a high-risk patient and requires combination chemotherapy. Appropriate and rapid diagnosis, management by specialized centers, and reduction of early deaths at the time of chemotherapy initiation have led to significant improvements in survival for patients with high-risk GTN. There is a crucial need to early identify high-risk GTN patients with increased death risk to organize their management in highly specialized centers. Objectives: To describe cases of gestational trophoblastic neoplasia that have resulted in death, particularly in a subgroup with a FIGO prognostic score ≥13, for who low-dose etoposide and cisplatin induction chemotherapy was recently shown to reduce early death rate. Study design: We identified 974 patients from the French Center for Trophoblastic Diseases who had a diagnosis of GTN between November 1999 and March 2014. Among 140 patients at high-risk of resistance to single-agent chemotherapy (FIGO score ≥7), 29 (21%) had a score ≥13. Mortality rate was estimated using the Kaplan-Meier method. Results: The 5-year overall mortality rate by excluding placental site trophoblastic tumors and epithelioid trophoblastic tumors was 2% for GTN patients [95% confidence interval (CI): 1.25-3.13%]. High-risk patients had a 5-year mortality rate of 12% (95% CI: 7.49-18.9%). Patients with a FIGO score ≥13 had a higher 5-year mortality rate (38.4%, 95% CI: 23.4-58.6%) and accounted for 52% of the deaths in the entire cohort. Early deaths, defined as those that occur within 4 weeks after treatment initiation, occurred in 8 patients out of the entire cohort. Six of them had a FIGO score ≥13 at presentation, of whom 5 had brain and/or liver metastases. Conclusion: Gestational trophoblastic diseases with a FIGO score ≥13 have an increased risk of early death. We suggest that a FIGO score ≥13 becomes a consensual criterion for prediction of GTN patients with increased risk of death, particularly early death. These patients justify management in highly specialized gestational trophoblastic disease centers and may benefit from the use of induction low-dose etoposide and cisplatin.
    Full-text · Article · Sep 2015 · American Journal of Obstetrics and Gynecology
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    ABSTRACT: Background: Relationships between pharmacokinetic (PK) parameters of etoposide and toxicity survivals were reported in cancer patients treated at standard doses. The clinical impact of PK variations of etoposide high doses has never been explored in lymphoma patients. Patients and methods: The primary objective of LYMPK study was to prospectively assess the impact of etoposide PK parameters on outcomes in lymphoma patients receiving high-dose chemotherapy regimen (carmustine, cytarabine, etoposide and melphalan) followed by autologous stem cell transplant (ASCT). Individual etoposide PK parameters were estimated with a previously reported bi-compartment model using NONMEM(®) program. The impact of PK parameters on toxicity and survival was assessed using univariate/multivariate analyses. Results: A total of 91 patients with malignant lymphoma [non-Hodgkin's lymphoma (NHL): 79; Hodgkin's lymphoma: 12] at first line (n = 49) or relapse (n = 42) were enrolled in five centers. Large inter-individual variabilities in individual PK values were found for the same administration doses. In NHL patients, cumulative higher trough concentrations over the eight administrations of the first cycle (TotC min, categorized by the median 58.71 mg/L) had significant prognostic value regarding the 5-year progression-free survival (PFS: 73.6 vs 46.5 %, P = 0.015) and 5-year overall survival (OS: 74.0 vs 52.2 %, P = 0.034). Using a Cox model analysis, integrating disease settings (first line vs recurrent disease), simplified IPI and other prognostic factors, TotC min was the only significant independent prognostic factor influencing PFS, disease-specific survival and OS. Conclusion: This prospective study suggests survival of NHL patients treated with BEAM regimen and ASCT might be improved by increasing etoposide administration dose, or plasma concentration-based adjustment.
    No preview · Article · Sep 2015 · Cancer Chemotherapy and Pharmacology
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    ABSTRACT: Numerous oral anticancer chemotherapies are available. Non-adherence or over-adherence to these chemotherapies can lead to lowered efficacy and increased risk of adverse events. The objective of this study was to identify patients' adherence profiles using a qualitative-quantitative method. A capecitabine treatment was initiated for 38 patients with advanced breast or colorectal cancer. At inclusion, information on patients' beliefs was reported using a questionnaire. Later, Information on patients' relation to treatment was obtained from a sub-group during an interview with a sociologist. Questionnaires were analyzed using Multiple Classification Analysis to cluster patients. Treatment adherence was evaluated by an electronic medication event monitoring systems (MEMS caps) and then correlated with patient clusters. Interviews were analyzed to complete and explain results. 38 patients were enrolled between 2008 and 2011 and completed the questionnaire. Twenty had adherence measured with MEMS caps all along treatment. Between 4 and 6 months after inclusion, 16 patients were interviewed. Patient profile B (retired, with a regular life, surrounded by a relative's attention to drug adherence, with a low educational level) was statistically associated with adequate adherence (p = 0.049). A tendency for lower adherence was observed among more highly educated patients with an irregular, active life (NS). All patients taking capecitabine demonstrated a risk of over-adherence, potentiating side effects. These encouraging primary results suggest that further studies should be undertaken and that educational programs tailored to patient profiles should be evaluated to enhance adherence for those who need it and to empower all patients to manage treatment side effects.
    Preview · Article · Jul 2015 · BMC Research Notes
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    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.
    No preview · Article · Jun 2015 · Annals of Surgical Oncology
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    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.
    No preview · Article · May 2015 · Future Oncology
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    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.
    No preview · Article · May 2015 · Future Oncology
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    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.
    Full-text · Article · Apr 2015 · CPT: Pharmacometrics and Systems Pharmacology
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    Full-text · Dataset · Feb 2015
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    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.
    No preview · Article · Jan 2015 · Journal of Clinical Pharmacy and Therapeutics
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    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.
    Full-text · Article · Jan 2015 · Bulletin du cancer
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    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.
    No preview · Article · Jan 2015 · Critical Reviews in Oncology/Hematology
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    ABSTRACT: We present a system of nonlinear ordinary differential equations used to quantify the complex dynamics of the interactions between tumor growth, vasculature generation, and antiangiogenic treatment. The primary dataset consists of longitudinal tumor size measurements (1,371 total observations) in 105 colorectal tumor-bearing mice. Mice received single or combination administration of sunitinib, an antiangiogenic agent, and/or irinotecan, a cytotoxic agent. Depending on the dataset, parameter estimation was performed either using a mixed-effect approach or by nonlinear least squares. Through a log-likelihood ratio test, we conclude that there is a potential synergistic interaction between sunitinib when administered in combination with irinotecan in preclinical settings. Model simulations were then compared to data from a follow-up preclinical experiment. We conclude that the model has predictive value in identifying the therapeutic window in which the timing between the administrations of these two drugs is most effective.
    Preview · Article · Jan 2015
  • O Bylicki · H K Gan · F Joly · D Maillet · B You · J Péron
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    ABSTRACT: Background: 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. Design: All phase III medical oncology RCTs published between 2007 and 2011 were reviewed according to the 2013 PROs CONSORT recommendations and an 11-point PROs reporting quality score (PRORQS) was defined based on the criteria. Results: The majority of trials did not report on PROs at all (201 of 325; 62%). Of the remaining 124 trials, the mean PRORQS score was 5.0 on an 11-point scale. The items related to methods of PROs collection and analysis were poorly reported (Description of the prespecified PRO hypothesis: 26% of RCTs; methods for PRO data collection (paper, telephone, electronic, other): 16%; statistical approaches for managing missing data: 37%). The only factor significantly associated with improved PROs reporting was where PROs reporting was the subject of a dedicated secondary manuscript, as was the case in 36 of the 124 (29%) of RCTs. Conclusion: Despite their clinical relevance, our findings show that some aspects of PROs reporting may greatly be improved, especially critical methodological aspects of PROs collection and analysis. The exceptions were where PROs were described in PROs-specific secondary publication. Use of the 2013 PROs CONSORT extensions should be encouraged and their effects on PROs reporting subsequently reassessed.
    No preview · Article · Oct 2014 · Annals of Oncology
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    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.
    No preview · Article · Oct 2014 · Journal of Clinical Pharmacy and Therapeutics

Publication Stats

546 Citations
332.87 Total Impact Points

Institutions

  • 2007-2016
    • University of Lyon
      Lyons, Rhône-Alpes, France
  • 2015
    • HCL
      Naveen, Uttar Pradesh, India
  • 2007-2015
    • Claude Bernard University Lyon 1
      • Equipe de recherche en ciblage thérapeutique en oncologie
      Villeurbanne, Rhône-Alpes, France
    • Hospices Civils de Lyon
      Lyons, Rhône-Alpes, France
  • 2007-2014
    • Centre Hospitalier Lyon Sud
      Lyons, Rhône-Alpes, France
  • 2010-2012
    • The Princess Margaret Hospital
      Toronto, Ontario, Canada
  • 2010-2011
    • University Health Network
      Toronto, Ontario, Canada
  • 2009
    • Institut de Cancérologie Gustave Roussy
      • Department of Radiotherapy
      Villejuif, Île-de-France, France