A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.
Identifieur interne : 001312 ( Main/Exploration ); précédent : 001311; suivant : 001313A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.
Auteurs : Birgit Geoerger [France] ; Franck Bourdeaut [France] ; Steven G. Dubois [États-Unis] ; Matthias Fischer [Allemagne] ; James I. Geller [États-Unis] ; Nicholas G. Gottardo [Australie] ; Aurélien Marabelle [France] ; Andrew D J. Pearson ; Shakeel Modak [États-Unis] ; Thomas Cash [Géorgie (pays)] ; Giles W. Robinson [États-Unis] ; Marlyane Motta [États-Unis] ; Alessandro Matano [Suisse] ; Suraj G. Bhansali [États-Unis] ; Jason R. Dobson [États-Unis] ; Sudha Parasuraman [États-Unis] ; Susan N. Chi [États-Unis]Source :
- Clinical cancer research : an official journal of the American Association for Cancer Research [ 1078-0432 ] ; 2017.
Abstract
Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off). Dose escalation was guided by a Bayesian logistic regression model with overdose control and real-time PK.Results: Thirty-two patients (median age, 5.5 years) received ribociclib 280, 350, or 470 mg/m(2) Three patients had dose-limiting toxicities of grade 3 fatigue (280 mg/m(2); n = 1) or grade 4 thrombocytopenia (470 mg/m(2); n = 2). Most common treatment-related adverse events (AE) were hematologic: neutropenia (72% all-grade/63% grade 3/4), leukopenia (63%/38%), anemia (44%/3%), thrombocytopenia (44%/28%), and lymphopenia (38%/19%), followed by vomiting (38%/0%), fatigue (25%/3%), nausea (25%/0%), and QTc prolongation (22%/0%). Ribociclib exposure was dose-dependent at 350 and 470 mg/m(2) [equivalent to 600 (RP2D)-900 mg in adults], with high interpatient variability. Best overall response was stable disease (SD) in nine patients (seven with neuroblastoma, two with primary CNS MRT); five patients achieved SD for more than 6, 6, 8, 12, and 13 cycles, respectively.Conclusions: Ribociclib demonstrated acceptable safety and PK in pediatric patients. MTD (470 mg/m(2)) and RP2D (350 mg/m(2)) were equivalent to those in adults. Observations of prolonged SD support further investigation of ribociclib combined with other agents in neuroblastoma and MRT. Clin Cancer Res; 23(10); 2433-41. ©2017 AACR.
DOI: 10.1158/1078-0432.CCR-16-2898
PubMed: 28432176
Affiliations:
- Allemagne, Australie, France, Géorgie (pays), Suisse, États-Unis
- Auvergne-Rhône-Alpes, Massachusetts, New Jersey, Ohio, Rhône-Alpes, Tennessee, État de New York, Île-de-France
- Lyon, Paris
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">A Phase I Study of the CDK4/6 Inhibitor Ribociclib (LEE011) in Pediatric Patients with Malignant Rhabdoid Tumors, Neuroblastoma, and Other Solid Tumors.</title><author><name sortKey="Geoerger, Birgit" sort="Geoerger, Birgit" uniqKey="Geoerger B" first="Birgit" last="Geoerger">Birgit Geoerger</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric and Adolescent Oncology, Gustave Roussy and UMR 8203, CNRS, Univ. Paris-Sud, Villejuif, France. birgit.geoerger@gustaveroussy.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Pediatric and Adolescent Oncology, Gustave Roussy and UMR 8203, CNRS, Univ. Paris-Sud, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Bourdeaut, Franck" sort="Bourdeaut, Franck" uniqKey="Bourdeaut F" first="Franck" last="Bourdeaut">Franck Bourdeaut</name><affiliation wicri:level="3"><nlm:affiliation>Institut Curie, PSL Research University, Department of Pediatric Oncology and INSERM U830, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, PSL Research University, Department of Pediatric Oncology and INSERM U830, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dubois, Steven G" sort="Dubois, Steven G" uniqKey="Dubois S" first="Steven G" last="Dubois">Steven G. Dubois</name><affiliation wicri:level="2"><nlm:affiliation>Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Fischer, Matthias" sort="Fischer, Matthias" uniqKey="Fischer M" first="Matthias" last="Fischer">Matthias Fischer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty and Center for Molecular Medicine Cologne (CMMC), University of Cologne; Max Planck Institute for Metabolism Research, Cologne, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty and Center for Molecular Medicine Cologne (CMMC), University of Cologne; Max Planck Institute for Metabolism Research, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Geller, James I" sort="Geller, James I" uniqKey="Geller J" first="James I" last="Geller">James I. Geller</name><affiliation wicri:level="2"><nlm:affiliation>UC Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>UC Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati</wicri:cityArea></affiliation></author><author><name sortKey="Gottardo, Nicholas G" sort="Gottardo, Nicholas G" uniqKey="Gottardo N" first="Nicholas G" last="Gottardo">Nicholas G. Gottardo</name><affiliation wicri:level="1"><nlm:affiliation>Princess Margaret Hospital for Children, Perth, Western Australia, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Princess Margaret Hospital for Children, Perth, Western Australia</wicri:regionArea><wicri:noRegion>Western Australia</wicri:noRegion></affiliation></author><author><name sortKey="Marabelle, Aurelien" sort="Marabelle, Aurelien" uniqKey="Marabelle A" first="Aurélien" last="Marabelle">Aurélien Marabelle</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Pediatric HematoOncology, Léon Bérard Cancer Center, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institute for Pediatric HematoOncology, Léon Bérard Cancer Center, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Pearson, Andrew D J" sort="Pearson, Andrew D J" uniqKey="Pearson A" first="Andrew D J" last="Pearson">Andrew D J. Pearson</name><affiliation><nlm:affiliation>The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, The Royal Marsden Hospital, Sutton, United Kingdom (Retired).</nlm:affiliation><wicri:noCountry code="subField">United Kingdom (Retired)</wicri:noCountry></affiliation></author><author><name sortKey="Modak, Shakeel" sort="Modak, Shakeel" uniqKey="Modak S" first="Shakeel" last="Modak">Shakeel Modak</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Cash, Thomas" sort="Cash, Thomas" uniqKey="Cash T" first="Thomas" last="Cash">Thomas Cash</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia.</nlm:affiliation><country xml:lang="fr">Géorgie (pays)</country><wicri:regionArea>Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta</wicri:regionArea><wicri:noRegion>Atlanta</wicri:noRegion></affiliation></author><author><name sortKey="Robinson, Giles W" sort="Robinson, Giles W" uniqKey="Robinson G" first="Giles W" last="Robinson">Giles W. Robinson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea>Department of Oncology, St. Jude Children's Research Hospital, Memphis</wicri:cityArea></affiliation></author><author><name sortKey="Motta, Marlyane" sort="Motta, Marlyane" uniqKey="Motta M" first="Marlyane" last="Motta">Marlyane Motta</name><affiliation wicri:level="2"><nlm:affiliation>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Matano, Alessandro" sort="Matano, Alessandro" uniqKey="Matano A" first="Alessandro" last="Matano">Alessandro Matano</name><affiliation wicri:level="1"><nlm:affiliation>Translational Clinical Oncology, Novartis Pharma AG, Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Translational Clinical Oncology, Novartis Pharma AG, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation></author><author><name sortKey="Bhansali, Suraj G" sort="Bhansali, Suraj G" uniqKey="Bhansali S" first="Suraj G" last="Bhansali">Suraj G. 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Paris-Sud, Villejuif, France. birgit.geoerger@gustaveroussy.fr.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Department of Pediatric and Adolescent Oncology, Gustave Roussy and UMR 8203, CNRS, Univ. Paris-Sud, Villejuif</wicri:regionArea><wicri:noRegion>Villejuif</wicri:noRegion><wicri:noRegion>Villejuif</wicri:noRegion></affiliation></author><author><name sortKey="Bourdeaut, Franck" sort="Bourdeaut, Franck" uniqKey="Bourdeaut F" first="Franck" last="Bourdeaut">Franck Bourdeaut</name><affiliation wicri:level="3"><nlm:affiliation>Institut Curie, PSL Research University, Department of Pediatric Oncology and INSERM U830, Paris, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institut Curie, PSL Research University, Department of Pediatric Oncology and INSERM U830, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Dubois, Steven G" sort="Dubois, Steven G" uniqKey="Dubois S" first="Steven G" last="Dubois">Steven G. Dubois</name><affiliation wicri:level="2"><nlm:affiliation>Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston</wicri:cityArea></affiliation></author><author><name sortKey="Fischer, Matthias" sort="Fischer, Matthias" uniqKey="Fischer M" first="Matthias" last="Fischer">Matthias Fischer</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty and Center for Molecular Medicine Cologne (CMMC), University of Cologne; Max Planck Institute for Metabolism Research, Cologne, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Oncology and Hematology, University Children's Hospital of Cologne, Medical Faculty and Center for Molecular Medicine Cologne (CMMC), University of Cologne; Max Planck Institute for Metabolism Research, Cologne</wicri:regionArea><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion><wicri:noRegion>Cologne</wicri:noRegion></affiliation></author><author><name sortKey="Geller, James I" sort="Geller, James I" uniqKey="Geller J" first="James I" last="Geller">James I. Geller</name><affiliation wicri:level="2"><nlm:affiliation>UC Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Ohio</region></placeName><wicri:cityArea>UC Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati</wicri:cityArea></affiliation></author><author><name sortKey="Gottardo, Nicholas G" sort="Gottardo, Nicholas G" uniqKey="Gottardo N" first="Nicholas G" last="Gottardo">Nicholas G. Gottardo</name><affiliation wicri:level="1"><nlm:affiliation>Princess Margaret Hospital for Children, Perth, Western Australia, Australia.</nlm:affiliation><country xml:lang="fr">Australie</country><wicri:regionArea>Princess Margaret Hospital for Children, Perth, Western Australia</wicri:regionArea><wicri:noRegion>Western Australia</wicri:noRegion></affiliation></author><author><name sortKey="Marabelle, Aurelien" sort="Marabelle, Aurelien" uniqKey="Marabelle A" first="Aurélien" last="Marabelle">Aurélien Marabelle</name><affiliation wicri:level="3"><nlm:affiliation>Institute for Pediatric HematoOncology, Léon Bérard Cancer Center, Lyon, France.</nlm:affiliation><country xml:lang="fr">France</country><wicri:regionArea>Institute for Pediatric HematoOncology, Léon Bérard Cancer Center, Lyon</wicri:regionArea><placeName><region type="region">Auvergne-Rhône-Alpes</region><region type="old region">Rhône-Alpes</region><settlement type="city">Lyon</settlement></placeName></affiliation></author><author><name sortKey="Pearson, Andrew D J" sort="Pearson, Andrew D J" uniqKey="Pearson A" first="Andrew D J" last="Pearson">Andrew D J. Pearson</name><affiliation><nlm:affiliation>The Royal Marsden NHS Foundation Trust & Institute of Cancer Research, The Royal Marsden Hospital, Sutton, United Kingdom (Retired).</nlm:affiliation><wicri:noCountry code="subField">United Kingdom (Retired)</wicri:noCountry></affiliation></author><author><name sortKey="Modak, Shakeel" sort="Modak, Shakeel" uniqKey="Modak S" first="Shakeel" last="Modak">Shakeel Modak</name><affiliation wicri:level="2"><nlm:affiliation>Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York</wicri:cityArea></affiliation></author><author><name sortKey="Cash, Thomas" sort="Cash, Thomas" uniqKey="Cash T" first="Thomas" last="Cash">Thomas Cash</name><affiliation wicri:level="1"><nlm:affiliation>Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta, Georgia.</nlm:affiliation><country xml:lang="fr">Géorgie (pays)</country><wicri:regionArea>Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta</wicri:regionArea><wicri:noRegion>Atlanta</wicri:noRegion></affiliation></author><author><name sortKey="Robinson, Giles W" sort="Robinson, Giles W" uniqKey="Robinson G" first="Giles W" last="Robinson">Giles W. Robinson</name><affiliation wicri:level="2"><nlm:affiliation>Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Tennessee</region></placeName><wicri:cityArea>Department of Oncology, St. Jude Children's Research Hospital, Memphis</wicri:cityArea></affiliation></author><author><name sortKey="Motta, Marlyane" sort="Motta, Marlyane" uniqKey="Motta M" first="Marlyane" last="Motta">Marlyane Motta</name><affiliation wicri:level="2"><nlm:affiliation>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Matano, Alessandro" sort="Matano, Alessandro" uniqKey="Matano A" first="Alessandro" last="Matano">Alessandro Matano</name><affiliation wicri:level="1"><nlm:affiliation>Translational Clinical Oncology, Novartis Pharma AG, Basel, Switzerland.</nlm:affiliation><country xml:lang="fr">Suisse</country><wicri:regionArea>Translational Clinical Oncology, Novartis Pharma AG, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation></author><author><name sortKey="Bhansali, Suraj G" sort="Bhansali, Suraj G" uniqKey="Bhansali S" first="Suraj G" last="Bhansali">Suraj G. Bhansali</name><affiliation wicri:level="2"><nlm:affiliation>Clinical Pharmacology, Translational Clinical Oncology, Novartis Institutes for BioMedical Research, East Hanover, New Jersey.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">New Jersey</region></placeName><wicri:cityArea>Clinical Pharmacology, Translational Clinical Oncology, Novartis Institutes for BioMedical Research, East Hanover</wicri:cityArea></affiliation></author><author><name sortKey="Dobson, Jason R" sort="Dobson, Jason R" uniqKey="Dobson J" first="Jason R" last="Dobson">Jason R. Dobson</name><affiliation wicri:level="2"><nlm:affiliation>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Parasuraman, Sudha" sort="Parasuraman, Sudha" uniqKey="Parasuraman S" first="Sudha" last="Parasuraman">Sudha Parasuraman</name><affiliation wicri:level="2"><nlm:affiliation>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Translational Clinical Oncology, Novartis Institutes for BioMedical Research, Cambridge</wicri:cityArea></affiliation></author><author><name sortKey="Chi, Susan N" sort="Chi, Susan N" uniqKey="Chi S" first="Susan N" last="Chi">Susan N. Chi</name><affiliation wicri:level="2"><nlm:affiliation>Pediatric NeuroOncology, DanaFarber Cancer Institute, Boston, Massachusetts.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Massachusetts</region></placeName><wicri:cityArea>Pediatric NeuroOncology, DanaFarber Cancer Institute, Boston</wicri:cityArea></affiliation></author></analytic><series><title level="j">Clinical cancer research : an official journal of the American Association for Cancer Research</title><idno type="ISSN">1078-0432</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Purpose: The cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib (LEE011), displayed preclinical activity in neuroblastoma and malignant rhabdoid tumor (MRT) models. In this phase I study, the maximum tolerated dose (MTD) and recommended phase II dose (RP2D), safety, pharmacokinetics (PK), and preliminary activity of single-agent ribociclib were investigated in pediatric patients with neuroblastoma, MRT, or other cyclin D-CDK4/6-INK4-retinoblastoma pathway-altered tumors.Experimental Design: Patients (aged 1-21 years) received escalating once-daily oral doses of ribociclib (3-weeks-on/1-week-off). Dose escalation was guided by a Bayesian logistic regression model with overdose control and real-time PK.Results: Thirty-two patients (median age, 5.5 years) received ribociclib 280, 350, or 470 mg/m(2) Three patients had dose-limiting toxicities of grade 3 fatigue (280 mg/m(2); n = 1) or grade 4 thrombocytopenia (470 mg/m(2); n = 2). Most common treatment-related adverse events (AE) were hematologic: neutropenia (72% all-grade/63% grade 3/4), leukopenia (63%/38%), anemia (44%/3%), thrombocytopenia (44%/28%), and lymphopenia (38%/19%), followed by vomiting (38%/0%), fatigue (25%/3%), nausea (25%/0%), and QTc prolongation (22%/0%). Ribociclib exposure was dose-dependent at 350 and 470 mg/m(2) [equivalent to 600 (RP2D)-900 mg in adults], with high interpatient variability. Best overall response was stable disease (SD) in nine patients (seven with neuroblastoma, two with primary CNS MRT); five patients achieved SD for more than 6, 6, 8, 12, and 13 cycles, respectively.Conclusions: Ribociclib demonstrated acceptable safety and PK in pediatric patients. MTD (470 mg/m(2)) and RP2D (350 mg/m(2)) were equivalent to those in adults. Observations of prolonged SD support further investigation of ribociclib combined with other agents in neuroblastoma and MRT. Clin Cancer Res; 23(10); 2433-41. ©2017 AACR.</div></front></TEI><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>France</li><li>Géorgie (pays)</li><li>Suisse</li><li>États-Unis</li></country><region><li>Auvergne-Rhône-Alpes</li><li>Massachusetts</li><li>New Jersey</li><li>Ohio</li><li>Rhône-Alpes</li><li>Tennessee</li><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Lyon</li><li>Paris</li></settlement></list><tree><noCountry><name sortKey="Pearson, Andrew D J" sort="Pearson, Andrew D J" uniqKey="Pearson A" first="Andrew D J" last="Pearson">Andrew D J. Pearson</name></noCountry><country name="France"><noRegion><name sortKey="Geoerger, Birgit" sort="Geoerger, Birgit" uniqKey="Geoerger B" first="Birgit" last="Geoerger">Birgit Geoerger</name></noRegion><name sortKey="Bourdeaut, Franck" sort="Bourdeaut, Franck" uniqKey="Bourdeaut F" first="Franck" last="Bourdeaut">Franck Bourdeaut</name><name sortKey="Marabelle, Aurelien" sort="Marabelle, Aurelien" uniqKey="Marabelle A" first="Aurélien" last="Marabelle">Aurélien Marabelle</name></country><country name="États-Unis"><region name="Massachusetts"><name sortKey="Dubois, Steven G" sort="Dubois, Steven G" uniqKey="Dubois S" first="Steven G" last="Dubois">Steven G. Dubois</name></region><name sortKey="Bhansali, Suraj G" sort="Bhansali, Suraj G" uniqKey="Bhansali S" first="Suraj G" last="Bhansali">Suraj G. Bhansali</name><name sortKey="Chi, Susan N" sort="Chi, Susan N" uniqKey="Chi S" first="Susan N" last="Chi">Susan N. Chi</name><name sortKey="Dobson, Jason R" sort="Dobson, Jason R" uniqKey="Dobson J" first="Jason R" last="Dobson">Jason R. Dobson</name><name sortKey="Geller, James I" sort="Geller, James I" uniqKey="Geller J" first="James I" last="Geller">James I. Geller</name><name sortKey="Modak, Shakeel" sort="Modak, Shakeel" uniqKey="Modak S" first="Shakeel" last="Modak">Shakeel Modak</name><name sortKey="Motta, Marlyane" sort="Motta, Marlyane" uniqKey="Motta M" first="Marlyane" last="Motta">Marlyane Motta</name><name sortKey="Parasuraman, Sudha" sort="Parasuraman, Sudha" uniqKey="Parasuraman S" first="Sudha" last="Parasuraman">Sudha Parasuraman</name><name sortKey="Robinson, Giles W" sort="Robinson, Giles W" uniqKey="Robinson G" first="Giles W" last="Robinson">Giles W. Robinson</name></country><country name="Allemagne"><noRegion><name sortKey="Fischer, Matthias" sort="Fischer, Matthias" uniqKey="Fischer M" first="Matthias" last="Fischer">Matthias Fischer</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Gottardo, Nicholas G" sort="Gottardo, Nicholas G" uniqKey="Gottardo N" first="Nicholas G" last="Gottardo">Nicholas G. Gottardo</name></noRegion></country><country name="Géorgie (pays)"><noRegion><name sortKey="Cash, Thomas" sort="Cash, Thomas" uniqKey="Cash T" first="Thomas" last="Cash">Thomas Cash</name></noRegion></country><country name="Suisse"><noRegion><name sortKey="Matano, Alessandro" sort="Matano, Alessandro" uniqKey="Matano A" first="Alessandro" last="Matano">Alessandro Matano</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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