Wick W.,University of Heidelberg |
Wick W.,German Cancer Research Center |
Steinbach J.P.,Goethe University Frankfurt |
Platten M.,University of Heidelberg |
And 10 more authors.
Neuro-Oncology | Year: 2013
BackgroundThis study's primary objective was evaluation of the progression-free survival rate at 6 months (PFS-6) in patients with newly diagnosed glioblastoma without O6-methylguanine-DNA-methyltransferase (MGMT) promoter hypermethylation postsurgically treated with enzastaurin before and concomitantly with radiation therapy, followed by enzastaurin maintenance therapy. PFS-6 of at least 55% was set to be relevant compared with the data of the EORTC 26981/22981 NCIC CE.3 trial.MethodsAdult patients with a life expectancy of at least 12 weeks who were newly diagnosed with a histologically proven supratentorial glioblastoma without MGMT promoter hypermethylation were eligible. Patients were treated with enzastaurin prior to, concomitantly with, and after standard partial brain radiotherapy. Here we report on a multicenter, open-label, uncontrolled phase II study of patients with newly diagnosed glioblastoma without MGMT promoter hypermethylation treated with enzastaurin and radiation therapy within 4 study periods.ResultsPFS-6 was 53.6% (95% confidence interval [CI]: 39.8-65.6). The median overall survival was 15.0 months (95% CI: 11.9-17.9) for all patients, 3.9 months (95% CI: 0.8-9.0) for patients with biopsy, 15.4 months (95% CI: 10.1-17.9) for patients with partial resection, and 18.9 months (95% CI: 13.9-28.5) for patients with complete resection. The safety profile in this study was as expected from previous trials, and the therapy was well tolerated.ConclusionsPFS-6 missed the primary planned outcome of 55%. The secondary exploratory analysis according to resection status of the different subgroups of patients with biopsies, partial resection, and complete resection demonstrates the strong prognostic influence of resection on overall survival. © 2013 © The Author(s) 2013. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: email@example.com.
Davies M.,University of Leicester |
Heller S.,University of Sheffield |
Sreenan S.,Royal College of Surgeons in Ireland |
Sapin H.,Lilly France |
And 3 more authors.
Diabetes Care | Year: 2013
OBJECTIVE-This multicenter, open-label, parallel-arm study compared the efficacy and safety of exenatide once weekly (EQW) with titrated insulin detemir in patients with type 2 diabetes inadequately controlled with metformin (with or without sulfonylureas). RESEARCH DESIGN ANDMETHODS-Patients were randomized to EQW (2 mg) or detemir (once or twice daily, titrated to achieve fasting plasma glucose ≤5.5 mmol/L) for 26 weeks. The primary outcome was proportion of patients achieving A1C $le;7.0% and weight loss ≥1.0 kg at end point, analyzed by means of logistic regression. Secondary outcomes included measures of glycemic control, cardiovascular risk factors, and safety and tolerability. RESULTS-Of 216 patients (intent-to-treat population), 111 received EQWand 105 received detemir. Overall, 44.1% (95% CI, 34.7-53.9) of EQW-treated patients compared with 11.4% (6.0-19.1) of detemir-treated patients achieved the primary outcome (P < 0.0001). Treatment with EQWresulted in significantly greater reductions than detemir in A1C (least-square mean ±SE, -1.30±0.08%vs. -0.88±0.08%; P < 0.0001) and weight (-2.7±0.3 kg vs. +0.8±0.4 kg; P < 0.0001). Gastrointestinal- related and injection site-related adverse events occurredmore frequently with EQWthan with detemir. There was nomajor hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%) patients in the detemir group experienced minor hypoglycemia; only one event occurred without concomitant sulfonylureas (detemir group). CONCLUSIONS-Treatment with EQW resulted in a significantly greater proportion of patients achieving target A1C and weight loss than treatment with detemir, with a low risk of hypoglycemia. These results suggest that EQWis a viable alternative to insulin detemir treatment in patients with type 2 diabetes with inadequate glycemic control using oral antidiabetes drugs. © 2013 by the American Diabetes Association.
Ghobrial I.M.,Dana-Farber Cancer Institute |
Moreau P.,University of Nantes |
Harris B.,Dana-Farber Cancer Institute |
Poon T.,Dana-Farber Cancer Institute |
And 7 more authors.
Clinical Cancer Research | Year: 2012
Purpose: Enzastaurin is a serine/threonine kinase inhibitor that showed antiangiogenic, antiproliferative, and proapoptotic properties in vitro and antitumor activity in vivo in a xenograft Waldenström macroglobulinemia (WM) model. These findings provided the rationale for a multicenter phase II trial of oral enzastaurin in previously treated patients with WM. Experimental design: Patients who were treated with 1 to 5 prior regimens and who had a baseline immunoglobulin M level 2 times or more the upper limit of normal received oral enzastaurin 250 mg twice daily (500 mg total) after a single loading dose (day 1, cycle 1) of 375 mg 3 times daily (1,125 mg total) for 8 cycles of 28 days each or until progressive disease. Six patients who progressed during treatment with enzastaurin had dexamethasone added per protocol. Results: From July 2008 to December 2010, 42 patients were enrolled. The objective response rate (RR) was 38.1% (2 partial and 14 minor responses). One patient had grade 3 leukopenia and one patient died during the study from septic shock; both events were considered drug related. A statistically significant association between RR and interleukin 15 (IL-15) was observed, suggesting that higher concentration levels of IL-15 may be associated with better response. Conclusion: Enzastaurin was active and well tolerated in previously treated patients with WM. Because of the small sample size of this uncontrolled study, further assessment of the relationship between IL-15 and response to enzastaurin in patients with WM is required. These results warrant further investigation of enzastaurin for the treatment of WM. ©2012 AACR.
Rosilio M.,Lilly France |
Huber-Lequesne C.,University of Paris Pantheon Sorbonne |
Sapin H.,Lilly France |
Carel J.-C.,University Paris Diderot |
And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012
Context: The prevalence of SHOX deficiency in children with short stature (SS) is variable in the literature and various genotypes have been identified. Objectives: The aim of our study was to determine the frequency and distribution of SHOX genotypes in a large sample of children with SS in France. Design, Setting, and Patients: Children were enrolled in 38 French pediatric endocrinology centers and were either diagnosed with Leri-Weill syndrome (LWS), idiopathic short stature (ISS), or disproportionate short stature (DSS). Intervention and Main Outcome Measure: SHOX analysis was performed centrally as part of the Genetics and Neuroendocrinology of Short Stature International Study observational study. We compared patients with (SHOX-D) and without SHOX deficiency (non-SHOX-D). Results: Among the 537 patients tested [58.3% females, mean age 11.0 (4.2) yr], 27.7% had SHOX deficiency (LWS, 48.9%; ISS, 16.9%; DSS, 18.8%). Mean height [-2.3 (0.9) SD score] was similar in SHOX-Dandnon-SHOX- Dpatients.Themajority of SHOX-D patients with LWS had either a deletion encompassing SHOX or a point mutation (69%), whereas 59% of those with ISS had a deletion downstream of SHOX in the enhancer region. The height of the parents carrying a deletion downstream of SHOX was higher than the height of the parents carrying the other gene anomalies. Conclusions: SHOX deletions and point mutations as well as downstream SHOX enhancer deletions were identified in almost one third of the patients tested. An anomaly in this latter region seemed to be linked to a milder phenotype. Although further confirmation is needed, we suggest that the enhancer region should be systematically analyzed in patients suspected of SHOX deficiency. Copyright © 2012 by The Endocrine Society.
Bordier L.,HOpital Begin |
Doucet J.,HOpital Saint Julien |
Boudet J.,Lilly France |
Bauduceau B.,HOpital Begin
Diabetes and Metabolism | Year: 2014
Aim: This article is an update of the relationship between type 2 diabetes (T2D), cognitive dysfunction and dementia in older people. Methods and results: The number of older patients consulting for diabetes who also exhibit cognitive difficulties is consistently growing because of the increased longevity of the population as a whole and, according to a number of studies, the increased risk of cognitive impairment and dementia in older diabetic patients. Many studies have demonstrated a link between poor glucose control and deteriorated cognitive function in diabetic patients. A history of severe hypoglycaemic episodes has also been associated with a greater risk of late-in-life cognitive deficits and dementia in patients with T2D. Several processes are thought to promote cognitive decline and dementia in diabetics. Based on both clinical and non-clinical findings, the factors most likely to alter brain function and structure are cerebrovascular complications of diabetes, alterations in glucose and insulin, and recurrent hypoglycaemia. Together with other diabetes complications, cognitive deficits contribute to functional impairment, increased frequency of depression-related symptoms, greater incidence of recurrent hypoglycaemia, poorer adherence to treatment and, finally, poorer prognosis, as evidenced by recent longitudinal studies. Conclusion: Clinical guidelines have recently been devised for older diabetic patients, particularly those with cognitive deficits and a reduced capacity to self-manage. In the most vulnerable patients, specific treatment strategies have been proposed for glycaemic control to limit metabolic decompensation and avoid the risk of hypoglycaemia. Educational measures, provided mainly to maintain patient autonomy and avoid hospital admission, have also been adapted according to patients' cognitive and functional status. © 2014 Elsevier Masson SAS.
Treatment persistence and changes in fracture risk, back pain, and quality of life amongst patients treated with teriparatide in routine clinical care in France: Results from the European Forsteo Observational Study
Rajzbaum G.,Groupe Hospitalier Paris Saint Joseph |
Grados F.,Center Hospitalier University |
Evans D.,Lilly France |
Liu-Leage S.,Lilly France |
And 2 more authors.
Joint Bone Spine | Year: 2014
Objectives: The European Forsteo Observational Study assessed the clinical fracture incidence, back pain, quality of life (QoL), and treatment persistence amongst post-menopausal women, who were prescribed teriparatide in routine care in eight European countries. We present the results for France, with health-insurance reimbursement criteria channel teriparatide to women with severe disease and limit treatment to 18. months. Methods: A representative sample of women initiating teriparatide in France was followed in routine care for 36. months. We described patients' characteristics at baseline and persistence to teriparatide (Kaplan-Meier analysis), fracture incidence, back pain, and QoL (EQ-5D) at baseline, 18 and 36. months follow-up (last-observation-carried-forward (LOCF) and mixed-models-for-repeated-measures (MMRM). Results: One hundred and sixteen rheumatologists included 309 patients, of whom 290 (93.9%) had at least one follow-up visit. Women's mean age (standard deviation) was 74.5. years (7.4) and 296 (95.8%) had greater or equal to two vertebral fractures prior to teriparatide initiation. Clinical fracture incidence, mainly vertebral fractures, decreased around 6. months after teriparatide initiation, and was sustained at 36. months (P=0.013) when most patients were treated by anti-resorptives. Back pain and EQ-5D measures improved significantly at 18 and 36. months (P<. 0.0001) in the LOCF analyses but did not improve in the EQ-5D VAS measure after covariate adjustment in the MMRM model. Median treatment duration was 17.4. months. Conclusion: French women initiating teriparatide in routine care had severe osteoporosis and showed good treatment persistence, consistent with France's insurance reimbursement criteria. Improvements in fracture risk and back pain began soon after treatment and was maintained at 36. months follow-up. © 2013 Société française de rhumatologie.
Myers J.,Medical Decision Modeling Inc |
Wielage R.C.,Medical Decision Modeling Inc |
Han B.,Eli Lilly and Company |
Price K.,Eli Lilly and Company |
And 3 more authors.
BMC Musculoskeletal Disorders | Year: 2014
Background: This meta-analysis assessed the efficacy of duloxetine versus other oral treatments used after failure of acetaminophen for management of patients with osteoarthritis. Methods. A systematic literature review of English language articles was performed in PUBMED, EMBASE, MedLine In-Process, Cochrane Library, and ClinicalTrials.gov between January 1985 and March 2013. Randomized controlled trials of duloxetine and all oral non-steroidal anti-inflammatory drugs and opioids were included if treatment was ≥12 weeks and the Western Ontario and McMaster Universities Index (WOMAC) total score was available. Studies were assessed for quality using the assessment tool from the National Institute for Health and Clinical Excellence guidelines for single technology appraisal submissions.WOMAC baseline and change from baseline total scores were extracted and standardized. A frequentist meta-analysis, meta-regression, and indirect comparison were performed using the DerSimonian-Laird and Bucher methods. Bayesian analyses with and without adjustment for study-level covariates were performed using noninformative priors. Results: Thirty-two publications reported 34 trials (2 publications each reported 2 trials) that met inclusion criteria. The analyses found all treatments except oxycodone (frequentist) and hydromorphone (frequentist and Bayesian) to be more effective than placebo. Indirect comparisons to duloxetine found no significant differences for most of the compounds. Some analyses showed evidence of a difference with duloxetine for etoricoxib (better), tramadol and oxycodone (worse), but without consistent results between analyses. Forest plots revealed positive trends in overall efficacy improvement with baseline scores. Adjusting for baseline, the probability duloxetine is superior to other treatments ranges between 15% to 100%.Limitations of this study include the low number of studies included in the analyses, the inclusion of only English language publications, and possible ecological fallacy associated with patient level characteristics. Conclusions: This analysis suggests no difference between duloxetine and other post-first line oral treatments for osteoarthritis (OA) in total WOMAC score after approximately 12 weeks of treatment. Significant results for 3 compounds (1 better and 2 worse) were not consistent across performed analyses. © 2014 Myers et al.; licensee BioMed Central Ltd.
Yamamoto N.,National Cancer Center Hospital |
Nokihara H.,National Cancer Center Hospital |
Yamada Y.,National Cancer Center Hospital |
Uenaka K.,Eli Lilly and Company |
And 5 more authors.
Cancer Chemotherapy and Pharmacology | Year: 2013
Purpose: LY2334737 is an oral gemcitabine prodrug. This Phase I study assessed the safety and tolerability of LY2334737 in Japanese patients with solid tumors and evaluated pharmacokinetics (PK), pharmacodynamics, and antitumor activity. Methods: Patients with advanced/metastatic solid tumors received escalating doses of LY2334737 once daily for 14 days, followed by a 7-day drug-free period. Cycles were repeated until discontinuation criteria were met. Results: Of 13 patients treated, 3 received 20 mg/day, 6 received 30 mg/day, 4 received 40 mg/day. On the 40 mg dose, 3 patients experienced dose-limiting toxicities (DLTs): hepatic toxicities (e.g., Grade [G]3/4 transaminase and G1-3 bilirubin elevation) and G4 thrombocytopenia; all 3 showed features of disseminated intravascular coagulation. One additional DLT occurred on the 30 mg dose (G3 transaminase elevation). Exploratory pharmacogenetic analyses identified a genetic variation in the CES2 gene potentially associated with these DLTs. PK data showed no clear relationship between the AUC of gemcitabine and its incorporation into leukocyte DNA; 2 of the 3 DLT patients had high incorporation. Two patients (30 mg/day) achieved stable disease with progression-free survival lasting 135 and 155 days. Conclusions: LY2334737 was tolerated by Japanese patients up to 30 mg/day. The toxicities observed at the 40 mg dose may require the development of alternative dosing schedules. © 2013 Springer-Verlag Berlin Heidelberg.
Mo D.,Eli Lilly and Company |
Blum W.F.,Eli Lilly and Company |
Rosilio M.,Lilly France |
Webb S.M.,Autonomous University of Barcelona |
And 2 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014
Context: Previous studies showed improvement in impaired quality of life (QoL) in adult patients with growth hormone (GH) deficiency (GHD) who were treated with GH; improvement was sustained over a few years after GH therapy. Objective: To evaluate the QoL over 10 years. Design: This was a prospective observational study. Setting: The study was conducted in clinical practice. Patients: 1436 adult patients with adult-onset (AO) GHD (mean age [standard deviation (SD)]: 49.0 [12.2] years; 49% female) and 96 with childhood-onset (CO) GHD (31.3 [10.0] years; 60% female) (total N = 1532). Intervention: GH therapy. Main Outcome Measures: QoL was measured by Questions on Life Satisfaction-Hypopituitarism (QLS-H) in countries where validated questionnaires and normative data for calculation of Z-scores were available. Change in QoL was tested by Student's t test and predicted by mixed-model repeated measures (MMRM) analysis. Results: At study entry, patients had diminished QoL Z-scores (mean [SD] AO, -1.55 [1.69]; CO -0.98 [1.32]). The largest QoL improvements were in the first year: mean (SD) increase 0.77 (1.37) for AO (P < .001) and 0.50 (1.37) for CO (P < .001). The initial improvement from study entry remained statistically significant throughout 10 years for AO and in years 1 to 4, 6, and 7 for CO (P < .05). MMRM analysis predicted a greater QoL improvement in those who were not depressed, lived in Europe, had poorer Z-scores at entry, had lower body mass index at entry, and had no impaired vision. Conclusion: These data suggest that GH replacement provides sustained improvement in QLS-H scores toward normality for up to 10 years. Copyright © 2014 by the Endocrine Society.
PubMed | SR Consulting, GCS CNCR and Lilly France
Type: | Journal: Therapie | Year: 2017
The way patients and their caregivers share information on various online platforms about health topics and their own experiential knowledge presents new potential environments for research, particularly as concerns health products. The information provided individually and voluntarily by patients who are members of these online communities is a new resource for identifying and understanding precisely how health products are used, assessing their effectiveness, quantifying potential adverse effects in real-life situations, detecting subtle signs that are significant for experts in pharmacovigilance and addiction studies, and developing new assessment tools to help form new working hypotheses. How patients freely express their experiences and feelings and the reality of what they share also opens the way for societal research into health products, a field that is still under-explored. Well-established regulations govern research into health products, which uses resources and methodologies that have changed little over the years. However, the development of online communities of patients presents new possibilities in this field. The challenge we face today is defining their place among traditional research techniques. This place cannot be accepted by all stakeholders unless we first establish a firm understanding of the advantages, limitations, and constraints of these communities. The round table on this topic endeavoured to: explore these issues and develop a better understanding of the phenomenon and the different varieties of online communities and networks for patients; identify possible advantages, special features, and methodological, regulatory, and ethical limitations that researchers currently face; and finally, to put forward the first recommendations in this growing field of research.