Maillet D.,Institute Of Cancerologie Des Hospices Civils Of Lyon Ic Hcl |
Gan H.K.,Medical Oncology Unit |
Gan H.K.,La Trobe University |
Blay J.-Y.,Center Leon Berard |
And 6 more authors.
European Journal of Cancer | Year: 2016
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. © 2015 Elsevier Ltd. Source
El-Madani M.,University Claude Bernard Lyon 1 |
El-Madani M.,National Research Center of Egypt |
Henin E.,University Claude Bernard Lyon 1 |
Lefort T.,Hospices Civils de Lyon |
And 14 more authors.
Future Oncology | Year: 2015
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. © 2015 Future Medicine Ltd. Source
You B.,University of Lyon |
You B.,Center Dinvestigation Of Therapeutiques En Oncologie Et Hematologie Of Lyon Citohl |
Salles G.,Institute Of Cancerologie Des Hospices Civils Of Lyon Ic Hcl |
Salles G.,University of Lyon |
And 14 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2015
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. © 2015 Springer-Verlag Berlin Heidelberg. Source
De Charry F.,Institute Of Cancerologie Des Hospices Civils Of Lyon Ic Hcl |
Colomban O.,University Claude Bernard Lyon 1 |
You B.,Institute Of Cancerologie Des Hospices Civils Of Lyon Ic Hcl |
You B.,University Claude Bernard Lyon 1 |
And 8 more authors.
Clinical Genitourinary Cancer | Year: 2016
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. © 2015 Elsevier Inc. Source
BRCA1 associated protein 1 (BAP1) expression in pleural diffuse malignant mesothelioma: A comparative cytological and histological analyses on 50 patients [Apport de l'expression protéique de BRCA1 associated protein 1 (BAP1) dans le diagnostic des mésothéliomes malins diffus pleuraux: Une analyse cytologique et histologique comparative sur une série de 50 patients]
Thivolet-Bejui F.,Institute Of Cancerologie Des Hospices Civils Of Lyon Ic Hcl |
Chalabreysse L.,Institute Of Cancerologie Des Hospices Civils Of Lyon Ic Hcl |
Piaton E.,Institute Of Cancerologie Des Hospices Civils Of Lyon Ic Hcl |
Traverse-Glehen A.,Institute Of Cancerologie Des Hospices Civils Of Lyon Ic Hcl |
And 12 more authors.
Annales de Pathologie | Year: 2016
Introduction: Diffuse malignant mesothelioma (MMD) is a rare disease. The diagnosis is difficult and needs an antibody panel. The tumor suppressor gene BRCA1 associated protein 1 (BAP1) is involved in several cancers, including MMD. Loss of BAP1 expression is correlated with BAP1 somatic or constitutional genetic defects. Our work assesses the value of integrating BAP1 in the panel of antibodies used for the diagnosis of MMD. Materials and methods: Immunohistochemical techniques were performed on cytological and histological specimens of MMD and adenocarcinoma pleural metastasis. Results: Of the 26 patients with MMD and the 24 patients with adenocarcinoma pleural metastasis, loss of BAP1 expression was observed in 11 (48%) and one adenocarcinoma (6%) on cytological specimens and in 12 MMD (48%) and in one adenocarcinoma (5%) on biopsy specimens. The concordance between immunocytochemistry and immunohistochemistry was 100%. The specificity of BAP1 was 100% on cytological and biopsy specimen for the diagnosis of malignancy in case of mesothelial proliferation. Discussion and conclusion: Loss of BAP1 expression is an indicator of MMD in a context of mesothelial proliferation. This immunohistochemistry could be integrated in the panel of immunostaining used for MMD diagnosis, either on histological or cytological samples. Furthermore, loss of BAP1 expression guides the patient to an oncology genetic counseling in order to eliminate a MMD developed as part of a constitutional genetic defect. © 2016 Elsevier Masson SAS. Source