Metronomic Etoposide/Cyclophosphamide/Celecoxib Regimen Given to Children and Adolescents with Refractory Cancer : A Preliminary Monocentric Study
Identifieur interne : 008B91 ( Main/Exploration ); précédent : 008B90; suivant : 008B92Metronomic Etoposide/Cyclophosphamide/Celecoxib Regimen Given to Children and Adolescents with Refractory Cancer : A Preliminary Monocentric Study
Auteurs : Nicolas Andre [France] ; Angelique Rome [France] ; Carole Coze [France] ; Laetitia Padovani [France] ; Eddy Pasquier [France, Australie] ; Laurence Camoin [France] ; Jean Claude Gentet [France]Source :
- Clinical therapeutics [ 0149-2918 ] ; 2008.
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- Pascal (Inist)
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- topic : Enfant.
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Abstract
Background: Metronomic chemotherapy (MC) is the administration of chemotherapy at doses below the maximal tolerated dose on a frequent schedule of administration, with no prolonged drug-free breaks. Objective: The aim of this research was to assess the effectiveness and tolerance of a metronomic etoposide/ cyclophosphamide/celecoxib regimen in children and adolescents with refractory cancer. Methods: This retrospective, single-center study evaluated the use of MC with etoposide 25 mg/m2. d-1 (days 1-14), cyclophosphamide 25 mg/m2. d-1 (days 15-28), and celecoxib 100 to 400 mg/d (days 1-28), in children with refractory, or high-risk relapsing, cancer. Adverse events were determined through laboratory analyses and investigator observations. Results: From January 2005 to December 2007, 17 children and adolescents were treated. The best responses observed were stabilizations of the disease that lasted over 20 weeks in 7 patients (41%). Most importantly, in 4 patients (24%) antalgic treatment could be transiently diminished or stopped, and in 1 patient (6%) oxygen support could be stopped for several weeks. Four grade IV platelet toxicities were noted in 3 patients; 2 grade IV anemia occurred in 2 patients (who had platelet and red blood cell transfusions before initiation of treatment); and 1 patient had grade III neutropenia. No other grade III or IV toxicities were noted. Grade II alopecia and stomatitis were observed in 1 patient and grade II vomiting was observed in 2 patients. One patient with meningeal carcinomatosis developed bilateral subdural hematoma for which the role of MC could not be ruled out. Circulating endothelial cells were elevated in 3 out of 3 patients in whom they were quantified and who were progressing while under MC. Conclusion: The MC regimen we report here was associated with disease stabilization without major toxicities. This assessment of MC in children and adolescents warrants further studies.
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wicri:level="1"><inist:fA14 i1="04"><s1>Children's Cancer Institute Australia, Pharmacoproteomics Croup, Children's Hospital</s1><s2>Randwick</s2><s3>AUS</s3><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Randwick</wicri:noRegion></affiliation></author><author><name sortKey="Camoin, Laurence" sort="Camoin, Laurence" uniqKey="Camoin L" first="Laurence" last="Camoin">Laurence Camoin</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Laboratoire d'hématologie, Hôpital de la Conception</s1><s2>Marseille</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Gentet, Jean Claude" sort="Gentet, Jean Claude" uniqKey="Gentet J" first="Jean Claude" last="Gentet">Jean Claude Gentet</name><affiliation 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type="city">Marseille</settlement></placeName></affiliation><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>INSERM UMR-777, CISMET (Cytosquelette et Intégration des Signaux du Micro-Environnement Tumoral), CRO2, Université d'Aix-Marseille</s1><s2>Marseille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation></author><author><name sortKey="Rome, Angelique" sort="Rome, Angelique" uniqKey="Rome A" first="Angelique" last="Rome">Angelique Rome</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Service d'Oncologie Pédiatrique, Hôpital pour Enfants de La Timone</s1><s2>Marseille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Coze, Carole" sort="Coze, Carole" uniqKey="Coze C" first="Carole" last="Coze">Carole Coze</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Service d'Oncologie Pédiatrique, Hôpital pour Enfants de La Timone</s1><s2>Marseille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Padovani, Laetitia" sort="Padovani, Laetitia" uniqKey="Padovani L" first="Laetitia" last="Padovani">Laetitia Padovani</name><affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Service de Radiothérapie, Hôpital de La Timone</s1><s2>Marseille</s2><s3>FRA</s3><sZ>4 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Pasquier, Eddy" sort="Pasquier, Eddy" uniqKey="Pasquier E" first="Eddy" last="Pasquier">Eddy Pasquier</name><affiliation wicri:level="4"><inist:fA14 i1="02"><s1>INSERM UMR-777, CISMET (Cytosquelette et Intégration des Signaux du Micro-Environnement Tumoral), CRO2, Université d'Aix-Marseille</s1><s2>Marseille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>5 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement><settlement type="city">Marseille</settlement></placeName><orgName type="university">Université d'Aix-Marseille</orgName></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Children's Cancer Institute Australia, Pharmacoproteomics Croup, Children's Hospital</s1><s2>Randwick</s2><s3>AUS</s3><sZ>5 aut.</sZ></inist:fA14><country>Australie</country><wicri:noRegion>Randwick</wicri:noRegion></affiliation></author><author><name sortKey="Camoin, Laurence" sort="Camoin, Laurence" uniqKey="Camoin L" first="Laurence" last="Camoin">Laurence Camoin</name><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Laboratoire d'hématologie, Hôpital de la Conception</s1><s2>Marseille</s2><s3>FRA</s3><sZ>6 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author><author><name sortKey="Gentet, Jean Claude" sort="Gentet, Jean Claude" uniqKey="Gentet J" first="Jean Claude" last="Gentet">Jean Claude Gentet</name><affiliation wicri:level="3"><inist:fA14 i1="01"><s1>Service d'Oncologie Pédiatrique, Hôpital pour Enfants de La Timone</s1><s2>Marseille</s2><s3>FRA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>France</country><placeName><region type="region">Provence-Alpes-Côte d'Azur</region><region type="old region">Provence-Alpes-Côte d'Azur</region><settlement type="city">Marseille</settlement></placeName></affiliation></author></analytic><series><title level="j" type="main">Clinical therapeutics</title><title level="j" type="abbreviated">Clin. ther.</title><idno type="ISSN">0149-2918</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Clinical therapeutics</title><title level="j" type="abbreviated">Clin. ther.</title><idno type="ISSN">0149-2918</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term><term>Antineoplastic agent</term><term>Cancerology</term><term>Celecoxib</term><term>Child</term><term>Cyclophosphamide</term><term>Endothelial cell</term><term>Etoposide</term><term>Malignant tumor</term><term>Metronomic chemotherapy</term><term>Non steroidal antiinflammatory agent</term><term>Therapeutic protocol</term><term>Treatment resistance</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Etoposide</term><term>Cyclophosphamide</term><term>Anticancéreux</term><term>Célécoxib</term><term>Protocole thérapeutique</term><term>Enfant</term><term>Adolescent</term><term>Résistance traitement</term><term>Tumeur maligne</term><term>Cancérologie</term><term>Cellule endothéliale</term><term>Antiinflammatoire non stéroïde</term><term>Gène sis</term><term>Chimiothérapie métronomique</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Enfant</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Background: Metronomic chemotherapy (MC) is the administration of chemotherapy at doses below the maximal tolerated dose on a frequent schedule of administration, with no prolonged drug-free breaks. Objective: The aim of this research was to assess the effectiveness and tolerance of a metronomic etoposide/ cyclophosphamide/celecoxib regimen in children and adolescents with refractory cancer. Methods: This retrospective, single-center study evaluated the use of MC with etoposide 25 mg/m<sup>2</sup>. d<sup>-1</sup> (days 1-14), cyclophosphamide 25 mg/m<sup>2</sup>. d<sup>-1</sup> (days 15-28), and celecoxib 100 to 400 mg/d (days 1-28), in children with refractory, or high-risk relapsing, cancer. Adverse events were determined through laboratory analyses and investigator observations. Results: From January 2005 to December 2007, 17 children and adolescents were treated. The best responses observed were stabilizations of the disease that lasted over 20 weeks in 7 patients (41%). Most importantly, in 4 patients (24%) antalgic treatment could be transiently diminished or stopped, and in 1 patient (6%) oxygen support could be stopped for several weeks. Four grade IV platelet toxicities were noted in 3 patients; 2 grade IV anemia occurred in 2 patients (who had platelet and red blood cell transfusions before initiation of treatment); and 1 patient had grade III neutropenia. No other grade III or IV toxicities were noted. Grade II alopecia and stomatitis were observed in 1 patient and grade II vomiting was observed in 2 patients. One patient with meningeal carcinomatosis developed bilateral subdural hematoma for which the role of MC could not be ruled out. Circulating endothelial cells were elevated in 3 out of 3 patients in whom they were quantified and who were progressing while under MC. Conclusion: The MC regimen we report here was associated with disease stabilization without major toxicities. This assessment of MC in children and adolescents warrants further studies.</div></front></TEI><affiliations><list><country><li>Australie</li><li>France</li></country><region><li>Provence-Alpes-Côte d'Azur</li></region><settlement><li>Marseille</li></settlement><orgName><li>Université d'Aix-Marseille</li></orgName></list><tree><country name="France"><region name="Provence-Alpes-Côte d'Azur"><name sortKey="Andre, Nicolas" sort="Andre, Nicolas" uniqKey="Andre N" first="Nicolas" last="Andre">Nicolas Andre</name></region><name sortKey="Andre, Nicolas" sort="Andre, Nicolas" uniqKey="Andre N" first="Nicolas" last="Andre">Nicolas Andre</name><name sortKey="Camoin, Laurence" sort="Camoin, Laurence" uniqKey="Camoin L" first="Laurence" last="Camoin">Laurence Camoin</name><name sortKey="Coze, Carole" sort="Coze, Carole" uniqKey="Coze C" first="Carole" last="Coze">Carole Coze</name><name sortKey="Gentet, Jean Claude" sort="Gentet, Jean Claude" uniqKey="Gentet J" first="Jean Claude" last="Gentet">Jean Claude Gentet</name><name sortKey="Padovani, Laetitia" sort="Padovani, Laetitia" uniqKey="Padovani L" first="Laetitia" last="Padovani">Laetitia Padovani</name><name sortKey="Pasquier, Eddy" sort="Pasquier, Eddy" uniqKey="Pasquier E" first="Eddy" last="Pasquier">Eddy Pasquier</name><name sortKey="Rome, Angelique" sort="Rome, Angelique" uniqKey="Rome A" first="Angelique" last="Rome">Angelique Rome</name></country><country name="Australie"><noRegion><name sortKey="Pasquier, Eddy" sort="Pasquier, Eddy" uniqKey="Pasquier E" first="Eddy" last="Pasquier">Eddy Pasquier</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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