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Pancreatic Neoplasms: HELP
Articles by Gael Deplanque
Based on 9 articles published since 2010
(Why 9 articles?)

Between 2010 and 2020, G. Deplanque wrote the following 9 articles about Pancreatic Neoplasms.
+ Citations + Abstracts
1 Guideline Consensus statement on mandatory measurements in pancreatic cancer trials (COMM-PACT) for systemic treatment of unresectable disease. 2018

Ter Veer, Emil / van Rijssen, L Bengt / Besselink, Marc G / Mali, Rosa M A / Berlin, Jordan D / Boeck, Stefan / Bonnetain, Franck / Chau, Ian / Conroy, Thierry / Van Cutsem, Eric / Deplanque, Gael / Friess, Helmut / Glimelius, Bengt / Goldstein, David / Herrmann, Richard / Labianca, Roberto / Van Laethem, Jean-Luc / Macarulla, Teresa / van der Meer, Jonathan H M / Neoptolemos, John P / Okusaka, Takuji / O'Reilly, Eileen M / Pelzer, Uwe / Philip, Philip A / van der Poel, Marcel J / Reni, Michele / Scheithauer, Werner / Siveke, Jens T / Verslype, Chris / Busch, Olivier R / Wilmink, Johanna W / van Oijen, Martijn G H / van Laarhoven, Hanneke W M. ·Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Surgery, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. · Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA. · Department of Internal Medicine III, Comprehensive Cancer Center, Klinikum Grosshadern, Ludwig-Maximilians-University of Munich, Munich, Germany. · Methodology and Quality of Life in Oncology Unit, University Hospital of Besançon, Besançon, France. · Royal Marsden NHS Foundation Trust, London and Surrey, UK. · Department of Medical Oncology, Institut de Cancérologie de Lorraine and Lorraine University, Vandoeuvre-lès-Nancy, France. · Department of Gastroenterology and Digestive Oncology, University Hospitals Gasthuisberg Leuven and KU Leuven, Leuven, Belgium. · Department of Oncology, Hôpital Riviera-Chablais, Vevey, Switzerland. · Department of Surgery, Technical University of Munich, Klinikum rechts der Isar, Munich, Germany. · Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. · Nelune Cancer Centre, Prince of Wales Hospital, Prince of Wales Clinical School University of New South Wales, Randwick, NSW, Australia. · Department of Medical Oncology, University Hospital Basel, Basel, Switzerland. · Cancer Center, ASST Papa Giovanni XXIII, Bergamo, Italy. · Department of Gastroenterology, Gastrointestinal Cancer Unit, Erasme University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Vall d'Hebron University Hospital (HUVH), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain. · Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK. · Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Tokyo, Japan. · Gastrointestinal Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, New York, NY, USA. · Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany; Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany. · Department of Oncology, Karmanos Cancer Center, Wayne State University, Detroit, MI, USA. · Department of Medical Oncology, IRCCS San Raffaele Scientific Institute, Milan, Italy. · Department of Internal Medicine I, Medical University Vienna, Vienna, Austria. · Division of Solid Tumor Translational Oncology, West German Cancer Cancer, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK, partner site Essen) and German Cancer Research Center, DKFZ, Heidelberg, Germany. · Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium. · Department of Medical Oncology, Cancer Center Amsterdam, Academic Medical Center, Amsterdam, Netherlands. Electronic address: h.vanlaarhoven@amc.uva.nl. ·Lancet Oncol · Pubmed #29508762.

ABSTRACT: Variations in the reporting of potentially confounding variables in studies investigating systemic treatments for unresectable pancreatic cancer pose challenges in drawing accurate comparisons between findings. In this Review, we establish the first international consensus on mandatory baseline and prognostic characteristics in future trials for the treatment of unresectable pancreatic cancer. We did a systematic literature search to find phase 3 trials investigating first-line systemic treatment for locally advanced or metastatic pancreatic cancer to identify baseline characteristics and prognostic variables. We created a structured overview showing the reporting frequencies of baseline characteristics and the prognostic relevance of identified variables. We used a modified Delphi panel of two rounds involving an international panel of 23 leading medical oncologists in the field of pancreatic cancer to develop a consensus on the various variables identified. In total, 39 randomised controlled trials that had data on 15 863 patients were included, of which 32 baseline characteristics and 26 prognostic characteristics were identified. After two consensus rounds, 23 baseline characteristics and 12 prognostic characteristics were designated as mandatory for future pancreatic cancer trials. The COnsensus statement on Mandatory Measurements in unresectable PAncreatic Cancer Trials (COMM-PACT) identifies a mandatory set of baseline and prognostic characteristics to allow adequate comparison of outcomes between pancreatic cancer studies.

2 Clinical Trial TGFβ receptor inhibitor galunisertib is linked to inflammation- and remodeling-related proteins in patients with pancreatic cancer. 2019

Melisi, Davide / Garcia-Carbonero, Rocio / Macarulla, Teresa / Pezet, Denis / Deplanque, Gael / Fuchs, Martin / Trojan, Jorg / Kozloff, Mark / Simionato, Francesca / Cleverly, Ann / Smith, Claire / Wang, Shuaicheng / Man, Michael / Driscoll, Kyla E / Estrem, Shawn T / Lahn, Michael M F / Benhadji, Karim A / Tabernero, Josep. ·Digestive Molecular Clinical Oncology Research Unit, Section of Medical Oncology, Department of Medicine, Università degli studi di Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. davide.melisi@univr.it. · University Hospital Doce de Octubre, Institute of Health Research Hospital 12 de Octubre (imas12), UCM, CNIO, CIBERONC, Madrid, Spain. · Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Autonomous University of Barcelona, CIBERONC, Barcelona, Spain. · Digestive Surgery Service, CHU Clermont-Ferrand, University Clermont Auvergne, Clermont-Ferrand, France. · Medical Oncology, Saint Joseph Hospital, Paris, France. · Hospital Bogenhausen, Municipal Hospital Munich GmbH, Munich, Germany. · Goethe University Medical Center, Frankfurt, Germany. · Ingalls Memorial Hospital, Harvey, IL, USA. · Digestive Molecular Clinical Oncology Research Unit, Section of Medical Oncology, Department of Medicine, Università degli studi di Verona, Piazzale L.A. Scuro, 10, 37134, Verona, Italy. · Eli Lilly and Company, Erl Wood, UK. · BioStat Solutions, Inc, Frederick, MD, USA. · Eli Lilly and Company, Indianapolis, IN, USA. ·Cancer Chemother Pharmacol · Pubmed #30887178.

ABSTRACT: PURPOSE: Galunisertib, the first small molecule transforming growth factor beta (TGFβ) receptor inhibitor, plus gemcitabine resulted in the improvement of survival in patients with unresectable pancreatic cancer, but markers to identify patients likely to respond are lacking. METHODS: In the Phase 1b/2 JBAJ study, 156 patients were randomized 2:1 to galunisertib + gemcitabine (N = 104) or placebo + gemcitabine (N = 52). Clinical outcome data were integrated with baseline markers and pharmacodynamic markers while patients were on treatment, including circulating proteins using a multi-analyte panel, T cell subset evaluation, and miRNA profiling. RESULTS: Baseline biomarkers associated with overall prognosis regardless of treatment included CA19-9 and TGF-β1. In addition, IP-10, FSH, MIP-1α, and PAI-1 were potential predictive proteins. Baseline proteins that were changed during treatment included amphiregulin, CA15-3, cathepsin D, P-selectin, RAGE, sortilin, COMP, eotaxin-2, N-BNP, osteopontin, and thrombospondin-4. Plasma miRNA with potential prognostic value included miR-21-5p, miR-301a-3p, miR-210-3p, and miR-141-3p, while those with potential predictive value included miR-424-5p, miR-483-3p, and miR-10b-5p. CONCLUSIONS: Galunisertib + gemcitabine resulted in improvement of overall survival, and 4 proteins (IP-10, FSH, MIP-1α, PAI-1) were potentially predictive for this combination treatment. Future studies should also include baseline evaluation of miR-424-5p, miR-483-3p, and miR-10b-5p. TRIAL REGISTRATION: Clinicaltrials.gov NCT01373164.

3 Clinical Trial Galunisertib plus gemcitabine vs. gemcitabine for first-line treatment of patients with unresectable pancreatic cancer. 2018

Melisi, Davide / Garcia-Carbonero, Rocio / Macarulla, Teresa / Pezet, Denis / Deplanque, Gael / Fuchs, Martin / Trojan, Jorg / Oettle, Helmut / Kozloff, Mark / Cleverly, Ann / Smith, Claire / Estrem, Shawn T / Gueorguieva, Ivelina / Lahn, Michael M F / Blunt, Al / Benhadji, Karim A / Tabernero, Josep. ·University of Verona, Piazzale Ludovico Antonio Scuro, 10, 37134, Verona, Italy. davide.melisi@univr.it. · Oncology Department, Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12), UCM, CNIO, CIBERONC, Madrid, Spain. · Vall d'Hebron University Hospital Institute of Oncology (VHIO), CIBERONC, C/ Natzaret, 115-117, 08035, Barcelona, Spain. · Centre Hospitalier Universitaire, 1 Place Lucie Aubrac, 63003, Clermont-Ferrand, France. · Hôpital Riviera-Chablais, Avenue de la Prairie 3, 1800, Vevey, Switzerland. · Klinikum Bogenhausen, Städtisches Klinikum München GmbH, Englschalkinger Road 77, 81925, Munich, Germany. · Goethe University Medical Center, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany. · Onkologische und Hämatologische Schwerpunktpraxis, Friedrichshafen, Germany. · Ingalls Memorial Hospital, 71W. 156th St., Harvey, IL, 60426, USA. · Eli Lilly and Company, Erl Wood Manor, Windlesham, Surrey, GU20 6PH, UK. · formerly of Eli Lilly and Company, Indianapolis, IN, 46285, USA. · Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN, 46285, USA. · 6820 Wisconsin Ave., #8008, Bethesda, MD, 20815, USA. · Advaxis, Inc., 305 College Road East, Princeton, NJ, 08540, USA. · Eli Lilly and Company, 440 Route 22 East, Bridgewater, NJ, 08807, USA. · Vall d'Hebron University Hospital and Institute of Oncology (VHIO), CIBERONC, Universitat Autònoma de Barcelona, P. Vall d'Hebron 119-129, 08035, Barcelona, Spain. ·Br J Cancer · Pubmed #30318515.

ABSTRACT: BACKGROUND: Galunisertib is the first-in-class, first-in-human, oral small-molecule type I transforming growth factor-beta receptor (ALK5) serine/threonine kinase inhibitor to enter clinical development. The effect of galunisertib vs. placebo in patients with unresectable pancreatic cancer was determined. METHODS: This was a two-part, multinational study: phase 1b was a non-randomised, open-label, multicentre, and dose-escalation study; phase 2 was a randomised, placebo- and Bayesian-augmented controlled, double-blind study in patients with locally advanced or metastatic pancreatic adenocarcinoma considered candidates for first-line chemotherapy with gemcitabine. Patients were randomised 2:1 to galunisertib-gemcitabine (N = 104) or placebo-gemcitabine (N = 52). Gemcitabine dose was 1000 mg/m RESULTS: Dose-escalation suggested a 300-mg/day dose. Primary objective was met: median survival times were 8.9 and 7.1 months for galunisertib and placebo, respectively (hazard ratio [HR] = 0.79 [95% credible interval: 0.59-1.09] and posterior probability HR < 1 = 0.93). Lower baseline biomarkers macrophage inflammatory protein-1-alpha and interferon-gamma-induced protein 10 were associated with galunisertib benefit. CONCLUSIONS: Galunisertib-gemcitabine combination improved overall survival vs. gemcitabine in patients with unresectable pancreatic cancer, with minimal added toxicity. Future exploration of galunisertib in pancreatic cancer is ongoing in combination with durvalumab.

4 Clinical Trial Phase 2 placebo-controlled, double-blind trial of dasatinib added to gemcitabine for patients with locally-advanced pancreatic cancer. 2017

Evans, T R J / Van Cutsem, E / Moore, M J / Bazin, I S / Rosemurgy, A / Bodoky, G / Deplanque, G / Harrison, M / Melichar, B / Pezet, D / Elekes, A / Rock, E / Lin, C / Strauss, L / O'Dwyer, P J. ·Beatson West of Scotland Cancer Centre, University of Glasgow, Glasgow, UK. · Department of Oncology, University Hospitals Leuven and KU Leuven, Leuven, Belgium. · Princess Margaret Cancer, Toronto, Canada. · Federal State Budgetary Institution, Dubna, Russia. · Surgery, Florida Hospital, Tampa, Tampa, USA. · Oncology, St.László Teaching Hospital, Budapest, Hungary. · Medicine, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. · East and North Hertfordshire NHS Trust, Northwood, Middlesex, UK. · Department of Oncology, Lekarska Fakulta Univerzity Palackeho a Fakultni Nemocnice, Olomouc, Czech Republic. · CHU Estaing, Clermont-Ferrand, France. · Otsuka Pharmaceutical Development and Commercialization, Princeton. · Bristol-Myers Squibb Company, Princeton. · Abramson Cancer Center, University of Pennsylvania, Philadelphia, USA. ·Ann Oncol · Pubmed #27998964.

ABSTRACT: Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate with limited treatment options. Gemcitabine provides a marginal survival benefit for patients with advanced PDAC. Dasatinib is a competitive inhibitor of Src kinase, which is overexpressed in PDAC tumors. Dasatinib and gemcitabine were combined in a phase 1 clinical trial where stable disease was achieved in two of eight patients with gemcitabine-refractory PDAC. Patients and methods: This placebo-controlled, randomized, double-blind, phase II study compared the combination of gemcitabine plus dasatinib to gemcitabine plus placebo in patients with locally advanced, non-metastatic PDAC. Patients received gemcitabine 1000 mg/m2 (30-min IV infusion) on days 1, 8, 15 of a 28-day cycle combined with either 100 mg oral dasatinib or placebo tablets daily. The primary objective was overall survival (OS), with safety and progression-free survival (PFS) as secondary objectives. Exploratory endpoints included overall response rate, freedom from distant metastasis, pain and fatigue progression and response rate, and CA19-9 response rate. Results: There was no statistically significant difference in OS between the two treatment groups (HR = 1.16; 95% confidence interval [CI]: 0.81-1.65; P = 0.5656). Secondary and exploratory endpoint analyses also showed no statistically significant differences. The burden of toxicity was higher in the dasatinib arm. Conclusions: Dasatinib failed to show increased OS or PFS in patients with locally advanced PDAC. Alternative combinations or trial designs may show a role for src inhibition in PDAC treatment.

5 Clinical Trial FFCD-1004 Clinical Trial: Impact of Cytidine Deaminase Activity on Clinical Outcome in Gemcitabine-Monotherapy Treated Patients. 2015

Serdjebi, Cindy / Gagnière, Johan / Desramé, Jérôme / Fein, Francine / Guimbaud, Rosine / François, Eric / André, Thierry / Seitz, Jean-François / Montérymard, Carole / Arsene, Dominique / Volet, Julien / Abakar-Mahamat, Abakar / Lecomte, Thierry / Guerin-Meyer, Véronique / Legoux, Jean-Louis / Deplanque, Gaël / Guillet, Pierre / Ciccolini, Joseph / Lepage, Côme / Dahan, Laetitia. ·SMARTc, CRO2 INSERM UMR S_911, Marseille, France. · University Hospital of Clermont Ferrand, Clermont Ferrand, France. · Center Jean Mermoz, Lyon, France. · University Hospital of Besançon, Besançon, France. · University Hospital of Toulouse, Toulouse, France. · Center Antoine Lacassagne, Nice, France. · University Hospital of Saint-Antoine and Pierre et Marie Curie, Assistance Publique des Hôpitaux de Paris, Paris, France. · University Hospital of La Timone, Assistance Publique des Hôpitaux de Marseille, Marseille, France. · Fédération Francophone de Cancérologie Digestive FFCD, Dijon, France. · University Hospital of Caen, Caen, France. · University Hospital of Reims, Reims, France. · University Hospital of Nice, Nice, France. · University Hospital of Tours, Tours, France. · University Hospital of Angers, Angers, France. · Regional Hospital of Orleans, Orleans, France. · St Joseph Hospital, Paris, France. · Hospital of Toulon, Toulon, France. · University Hospital of Dijon, Dijon, France. ·PLoS One · Pubmed #26308942.

ABSTRACT: PURPOSE: Because cytidine deaminase (CDA) is the key enzyme in gemcitabine metabolism, numerous studies have attempted to investigate impact of CDA status (i.e. genotype or phenotype) on clinical outcome. To date, data are still controversial because none of these studies has fully investigated genotype-phenotype CDA status, pharmacokinetics and clinical outcome relationships in gemcitabine-treated patients. Besides, most patients were treated with gemcitabine associated with other drugs, thus adding a confounding factor. We performed a multicenter prospective clinical trial in gemcitabine-treated patients which aimed at investigating the link between CDA deficiency on the occurrence of severe toxicities and on pharmacokinetics, and studying CDA genotype-phenotype relationships. EXPERIMENTAL DESIGN: One hundred twenty patients with resected pancreatic adenocarcinoma eligible for adjuvant gemcitabine monotherapy were enrolled in this study promoted and managed by the Fédération Francophone de Cancérologie Digestive. Toxicities were graded according to National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4. They were considered severe for grade ≥ 3, and early when occurring during the first eight weeks of treatment. CDA status was evaluated using a double approach: genotyping for 79A>C and functional testing. Therapeutic drug monitoring of gemcitabine and its metabolite were performed on the first course of gemcitabine. RESULTS: Five patients out of 120 (i.e., 4.6%) were found to be CDA deficient (i.e., CDA activity <1.3 U/mg), and only one among them experienced early severe hematological toxicity. There was no statistically significant difference in CDA activity between patients experiencing hematological severe toxicities (28.44%) and patients who tolerated the treatment (71.56%). CDA genetic analysis failed in evidencing an impact in terms of toxicities or in CDA activity. Regarding pharmacokinetics, a wide inter-individual variability has been observed in patients. CONCLUSION: This study, which included only 4.6% of CDA-deficient patients, failed in identifying CDA status as a predictive marker of toxicities with gemcitabine. A lack of statistical power because of smoothing effect of CDA variability as compared with real life conditions could explain this absence of impact. TRIAL REGISTRATION: ClinicalTrials.gov NCT01416662.

6 Clinical Trial A randomized, placebo-controlled phase III trial of masitinib plus gemcitabine in the treatment of advanced pancreatic cancer. 2015

Deplanque, G / Demarchi, M / Hebbar, M / Flynn, P / Melichar, B / Atkins, J / Nowara, E / Moyé, L / Piquemal, D / Ritter, D / Dubreuil, P / Mansfield, C D / Acin, Y / Moussy, A / Hermine, O / Hammel, P. ·Department of Medical Oncology, Saint Joseph Hospital, Paris gdeplanque@hpsj.fr. · Department of Medical Oncology, University Hospital of Besançon, Besançon. · Department of Medical Oncology, University Hospital, Lille, France. · Metro-Minnesota Community Clinical Oncology Program, Park Nicollet Institute, Minneapolis, USA. · Department of Oncology, Palacký University Medical School & Teaching Hospital, Olomouc, Czech Republic. · Southeastern Medical Oncology Center, Goldsboro, USA. · Department of Clinical and Experimental Oncology, Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice, Poland. · Department of Biostatistics, University of Texas School of Public Health, Houston, USA. · Clinical Development, Acobiom, Montpellier. · Signaling, Hematopoiesis and Mechanism of Oncogenesis, Inserm U1068, CRCM, Marseille Institut Paoli-Calmettes, Marseille Aix-Marseille University, UM 105, Marseille CNRS, UMR7258, CRCM, Marseille Clinical Development, AB Science, Paris. · Clinical Development, AB Science, Paris. · Clinical Development, AB Science, Paris Department of Clinical Hematology, Necker Hospital, Paris INSERM UMR 1163, Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic Implications, Paris Paris Descartes - Sorbonne Paris Cité University, Imagine Institute, Paris CNRS ERL 8254, Paris Laboratory of Excellence GR-Ex, Paris National Reference Center on Mastocytosis (CEREMAST), Paris. · Department of Gastroenterology, Hôpital Beaujon, Clichy, France. ·Ann Oncol · Pubmed #25858497.

ABSTRACT: BACKGROUND: Masitinib is a selective oral tyrosine-kinase inhibitor. The efficacy and safety of masitinib combined with gemcitabine was compared against single-agent gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patients with inoperable, chemotherapy-naïve, PDAC were randomized (1 : 1) to receive gemcitabine (1000 mg/m(2)) in combination with either masitinib (9 mg/kg/day) or a placebo. The primary endpoint was overall survival (OS) in the modified intent-to-treat population. Secondary OS analyses aimed to characterize subgroups with poor survival while receiving single-agent gemcitabine with subsequent evaluation of masitinib therapeutic benefit. These prospectively declared subgroups were based on pharmacogenomic data or a baseline characteristic. RESULTS: Three hundred and fifty-three patients were randomly assigned to receive either masitinib plus gemcitabine (N = 175) or placebo plus gemcitabine (N = 178). Median OS was similar between treatment-arms for the overall population, at respectively, 7.7 and 7.1 months, with a hazard ratio (HR) of 0.89 (95% CI [0.70; 1.13]. Secondary analyses identified two subgroups having a significantly poor survival rate when receiving single-agent gemcitabine; one defined by an overexpression of acyl-CoA oxidase-1 (ACOX1) in blood, and another via a baseline pain intensity threshold (VAS > 20 mm). These subgroups represent a critical unmet medical need as evidenced from median OS of 5.5 months in patients receiving single-agent gemcitabine, and comprise an estimated 63% of patients. A significant treatment effect was observed in these subgroups for masitinib with median OS of 11.7 months in the 'ACOX1' subgroup [HR = 0.23 (0.10; 0.51), P = 0.001], and 8.0 months in the 'pain' subgroup [HR = 0.62 (0.43; 0.89), P = 0.012]. Despite an increased toxicity of the combination as compared with single-agent gemcitabine, side-effects remained manageable. CONCLUSIONS: The present data warrant initiation of a confirmatory study that may support the use of masitinib plus gemcitabine for treatment of PDAC patients with overexpression of ACOX1 or baseline pain (VAS > 20mm). Masitinib's effect in these subgroups is also supported by biological plausibility and evidence of internal clinical validation. TRIAL REGISTRATION: ClinicalTrials.gov:NCT00789633.

7 Clinical Trial Safety and activity of masitinib in combination with gemcitabine in patients with advanced pancreatic cancer. 2010

Mitry, Emmanuel / Hammel, Pascal / Deplanque, Gaël / Mornex, Françoise / Levy, Philippe / Seitz, Jean-François / Moussy, Alain / Kinet, Jean-Pierre / Hermine, Olivier / Rougier, Philippe / Raymond, Eric. ·Hépato-gastroentérologie et oncologie digestive, Assistance Publique des Hôpitaux de Paris, Hôpital Ambroise Paré, 92104, Boulogne Billancourt, France. ·Cancer Chemother Pharmacol · Pubmed #20364428.

ABSTRACT: PURPOSE: To evaluate the efficacy and safety of masitinib combined with gemcitabine in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Twenty-two non-randomised patients with unresectable, locally advanced (n = 9) or metastatic pancreatic cancer (n = 13) received oral masitinib (9 mg/kg/day) combined with standard gemcitabine. All patients were naive to systemic chemotherapy or radiotherapy. The primary endpoint was time-to-progression (TTP) with efficacy and safety analyses performed on the intent-to-treat population. Secondary endpoints included overall survival (OS), as well as, subgroup analyses according to baseline disease, and performance status. RESULTS: Overall median TTP was 6.4 months (95% CI [2.7-11.7]); 8.3 and 2.7 months, respectively, for locally advanced and metastatic patients; 6.4 and 0.8 months, respectively, for patients with KPS [80-100] or KPS [70]. Median OS was 7.1 months (95% CI [4.8-17.0]); 8.4 and 6.8 months for locally advanced or metastatic patients, respectively; 8.0 and 4.4 months in patients with KPS [80-100] or KPS [70], respectively. The 18-month observed survival rate was similar for locally advanced (22%) and metastatic patients (23%) and reached 28% for KPS [80-100] patients. The most common suspected adverse events were nausea, vomiting, rash, diarrhoea, peripheral oedema, anaemia, lymphopenia, thrombocytopenia, pyrexia, neutropenia, asthenia, leucopenia, and abdominal pain, and most were of grades 1-2 severity. CONCLUSIONS: The efficacy and safety of masitinib combined with gemcitabine are encouraging, with extended survival and median TTP that support initiation of a phase 3 trial.

8 Article Population Pharmacokinetics of Gemcitabine and dFdU in Pancreatic Cancer Patients Using an Optimal Design, Sparse Sampling Approach. 2017

Serdjebi, Cindy / Gattacceca, Florence / Seitz, Jean-François / Fein, Francine / Gagnière, Johan / François, Eric / Abakar-Mahamat, Abakar / Deplanque, Gael / Rachid, Madani / Lacarelle, Bruno / Ciccolini, Joseph / Dahan, Laetitia. ·*SMARTc, CRO2, UMR S_911, Aix-Marseille Université, Marseille, France; †IRCM, Institut de Recherche en Cancérologie de Montpellier, INSERM U1194, ICM, Université de Montpellier, Montpellier, France; ‡Digestive Oncology Unit, La Timone Hospital, AP-HM, Aix-Marseille Université, Marseille, France; §Gastroenterology Department, CHRU Besançon, Besançon, France; ¶Digestive Pathologies Department, CHU Clermont-Ferrand, Clermont-Ferrand, France; ‖Pôle de Médecine, Centre Antoine Lacassagne, Nice, France; **Institut Arnault Tzanck, Saint Laurent du Var, France; and ††Service Interdisciplinaire de Cancérologie, Riviera-Chablais Hospital, Vevey, Switzerland. ·Ther Drug Monit · Pubmed #28346313.

ABSTRACT: BACKGROUND: Gemcitabine remains a pillar in pancreatic cancer treatment. However, toxicities are frequently observed. Dose adjustment based on therapeutic drug monitoring might help decrease the occurrence of toxicities. In this context, this work aims at describing the pharmacokinetics (PK) of gemcitabine and its metabolite dFdU in pancreatic cancer patients and at identifying the main sources of their PK variability using a population PK approach, despite a sparse sampled-population and heterogeneous administration and sampling protocols. METHODS: Data from 38 patients were included in the analysis. The 3 optimal sampling times were determined using KineticPro and the population PK analysis was performed on Monolix. Available patient characteristics, including cytidine deaminase (CDA) status, were tested as covariates. Correlation between PK parameters and occurrence of severe hematological toxicities was also investigated. RESULTS: A two-compartment model best fitted the gemcitabine and dFdU PK data (volume of distribution and clearance for gemcitabine: V1 = 45 L and CL1 = 4.03 L/min; for dFdU: V2 = 36 L and CL2 = 0.226 L/min). Renal function was found to influence gemcitabine clearance, and body surface area to impact the volume of distribution of dFdU. However, neither CDA status nor the occurrence of toxicities was correlated to PK parameters. CONCLUSIONS: Despite sparse sampling and heterogeneous administration and sampling protocols, population and individual PK parameters of gemcitabine and dFdU were successfully estimated using Monolix population PK software. The estimated parameters were consistent with previously published results. Surprisingly, CDA activity did not influence gemcitabine PK, which was explained by the absence of CDA-deficient patients enrolled in the study. This work suggests that even sparse data are valuable to estimate population and individual PK parameters in patients, which will be usable to individualize the dose for an optimized benefit to risk ratio.

9 Article Pancreatic cancer: are more chemotherapy and surgery needed? 2017

Deplanque, Gaël / Demartines, Nicolas. ·Service d'Oncologie, Hôpital Riviera-Chablais, 1800 Vevey, Switzerland. Electronic address: gael.deplanque@gmail.com. · Service de Chirurgie Viscérale, Centre Hospitalier Universitaire Vaudois CHUV, 1011 Lausanne, Switzerland. ·Lancet · Pubmed #28129986.

ABSTRACT: -- No abstract --