📇 Rhumatologue · LA TRONCHE · (38) · Hospitalier

M GAEL ROTH

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3 raisons identifiées

Auteur de référence en rhumatologie
22 articles scientifiques publiés — un praticien à la pointe de la recherche
Référence presse grand public
Cité 1 fois dans les médias — pédagogie reconnue
Délais de RDV courts dans la région
120.1 rhumatos / 100 000 hab. — département bien doté

Rhumatologue

📍 LA TRONCHE (38)HospitalierRPPS 10100951812

6ans d'exercice (thèse 2020)

🇫🇷 Publications académiques françaises (8)

✨ Génération du profil synthétique IA en cours…

Thèses universitaires

Nouvelles signalisations impliquant les lysines-méthyltransférases SMYD2 et SMYD3 dans le cancer
2020
Signalling of SMYD2 and SMYD3 lysine methyl-transferases in pancreatic cancer

Données ANS publiques (Licence Ouverte 2.0) · Enrichissements MonRhumato 100 % opt-in · Toute personne référencée peut demander la suppression ou la rectification.

Top publications · les plus citées

Gemcitabine and Paclitaxel Versus Gemcitabine Alone After 5-Fluorouracil, Oxaliplatin, and Irinotecan in Metastatic Pancreatic Adenocarcinoma: A Randomized Phase III PRODIGE 65-UCGI 36-GEMPAX UNICANCER Study

Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024

📚 27 citations🎯 RCR 4.36Top 10% NIH🩺 Clinique

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PURPOSE GEMPAX was an open-label, randomized phase III clinical trial designed to assess the efficacy and tolerability of gemcitabine plus paclitaxel versus gemcitabine alone as second-line treatment for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously received 5-fluorouracil, oxaliplatin, and irinotecan. METHODS Patients with histologically or cytologically confirmed mPDAC were randomly assigned (2:1) to receive GEMPAX (paclitaxel 80 mg/m2 + gemcitabine 1,000 mg/m2; IV; once at day (D) 1, D8, and D15/arm A) or gemcitabine (arm B) alone once at D1, D8, and D15 every 28 days until progression, toxicity, or patient's decision. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), quality of life, and safety. RESULTS Overall, 211 patients (median age, 64 [30-86] years; 62% male) were included. After a median study follow-up for alive patients of 13.4 versus 13.8 months in arm A versus arm B, the median OS (95% CI) was 6.4 (5.2 to 7.4) versus 5.9 months (4.6 to 6.9; hazard ratio [HR], 0.87 [0.63 to 1.20]; P = 0.4095), the median PFS was 3.1 (2.2 to 4.3) versus 2.0 months (1.9 to 2.3; HR, 0.64 [0.47 to 0.89]; P = 0.0067), and the ORR was 17.1% (11.3 to 24.4) versus 4.2% (0.9 to 11.9; P = 0.008) in arm A versus arm B, respectively. Overall, 16.7% of patients in arm A and 2.9% in arm B discontinued their treatment because of adverse events (AEs). One grade 5 AE associated with both gemcitabine and paclitaxel was reported in arm A (acute respiratory distress), and 58.0% versus 27.1% of patients experienced grade ≥3 treatment-related AEs in arm A versus arm B, among which 15.2% versus 4.3% had anemia, 15.9% versus 15.7% had neutropenia, 19.6% versus 4.3% had thrombocytopenia, 10.1% versus 2.9% had asthenia and 12.3% versus 0.0% had neuropathy. CONCLUSION While GEMPAX did not meet the primary end point of OS versus gemcitabine alone in patients with mPDAC in the second-line setting, both PFS and ORR were significantly improved.

First-In-Human Effects of PPT1 Inhibition Using the Oral Treatment with GNS561/Ezurpimtrostat in Patients with Primary and Secondary Liver Cancers

Liver cancer · 2022

📚 27 citations🎯 RCR 2.23Top 23% NIH🔓 Open Access📄 PDF gratuit ↗

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Introduction: GNS561/Ezurpimtrostat is a first-in-class, orally bioavailable, small molecule that blocks cancer cell proliferation by inhibiting late-stage autophagy and dose-dependent build-up of enlarged lysosomes by interacting with the palmitoyl-protein thioesterase 1 (PPT1). Methods: This phase I, open-label, dose-escalation trial (3 + 3 design) explored two GNS561 dosing schedules: one single oral intake 3 times a week (Q3W) and twice daily (BID) continuous oral administration in patients with advanced hepatocellular carcinoma, cholangiocarcinoma, and pancreatic adenocarcinoma or colorectal adenocarcinomas with liver metastasis. The primary objective was to determine GNS561 recommended phase II dose (RP2D) and schedule. Secondary objectives included evaluation of the safety/tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of GNS561. Results: Dose escalation ranged from 50 to 400 mg Q3W to 200–300 mg BID. Among 26 evaluable patients for safety, 20 were evaluable for efficacy and no dose-limiting toxicity was observed. Adverse events (AEs) included gastrointestinal grade 1–2 events, primarily nausea and vomiting occurred in 13 (50%) and 14 (54%) patients, respectively, and diarrhea in 11 (42%) patients. Seven grade 3 AEs were reported (diarrhea, decreased appetite, fatigue, alanine aminotransferase, and aspartate aminotransferase increased). Q3W administration was associated with limited exposure and the BID schedule was preferred. At 200 mg BID GNS561, plasma and liver concentrations were comparable to active doses in animal models. Liver trough concentrations were much higher than in plasma a median time of 28 days of administration with a mean liver to plasma ratio of 9,559 (Min 149–Max 25,759), which is in accordance with rat preclinical data observed after repeated administration. PPT1 expression in cancer tissues in the liver was reduced upon GNS561 exposure. There was no complete or partial response. Five patients experienced tumor stable diseases (25%), including one minor response (−23%). Conclusion: Based on a favorable safety profile, exposure, and preliminary signal of activity, oral GNS561 RP2D was set at 200 mg BID. Studies to evaluate the antitumor activity of GNS561 in hepatocarcinoma cells and intrahepatic cholangiocarcinoma are to follow NCT 03316222.

Impact of the COVID-19 pandemic on disease stage and treatment for patients with pancreatic adenocarcinoma: A French comprehensive multicentre ambispective observational cohort study (CAPANCOVID)

European journal of cancer (Oxford, England : 1990) · 2022

📚 24 citations🎯 RCR 1.96🩺 Clinique🔓 Open Access📄 PDF gratuit ↗

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M GAEL ROTH

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Thèses universitaires

Publications académiques en France

Lieu de consultation

Tarifs & secteur de conventionnement

Prendre rendez-vous & contact

Articles de presse (1)

Top publications · les plus citées

Publications scientifiques (22) — classées par pathologie

Transversal12

Essai clinique3

Épidémiologie & registres2

Gériatrie2

Économie santé1

Pharmacovigilance1

Qualité de vie / PROMs1

Vraie vie / RWE1

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