Metronomic Etoposide/Cyclophosphamide/Celecoxib Regimen Given to Children and Adolescents with Refractory Cancer : A Preliminary Monocentric Study
Identifieur interne : 003073 ( PascalFrancis/Checkpoint ); précédent : 003072; suivant : 003074Metronomic 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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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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<author><name sortKey="Gentet, Jean Claude" sort="Gentet, Jean Claude" uniqKey="Gentet J" first="Jean Claude" last="Gentet">Jean Claude Gentet</name>
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<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>
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<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>
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<sZ>1 aut.</sZ>
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<fA14 i1="04"><s1>Children's Cancer Institute Australia, Pharmacoproteomics Croup, Children's Hospital</s1>
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<s3>AUS</s3>
<sZ>5 aut.</sZ>
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<fA14 i1="05"><s1>Laboratoire d'hématologie, Hôpital de la Conception</s1>
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<s3>FRA</s3>
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<fC01 i1="01" l="ENG"><s0>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.</s0>
</fC01>
<fC02 i1="01" i2="X"><s0>002B02</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE"><s0>Etoposide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG"><s0>Etoposide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA"><s0>Etopósido</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE"><s0>Cyclophosphamide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG"><s0>Cyclophosphamide</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA"><s0>Ciclofosfamida</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE"><s0>Anticancéreux</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG"><s0>Antineoplastic agent</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA"><s0>Anticanceroso</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE"><s0>Célécoxib</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG"><s0>Celecoxib</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA"><s0>Celecoxib</s0>
<s2>NK</s2>
<s2>FR</s2>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE"><s0>Protocole thérapeutique</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG"><s0>Therapeutic protocol</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA"><s0>Protocolo terapéutico</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE"><s0>Enfant</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG"><s0>Child</s0>
<s5>06</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA"><s0>Niño</s0>
<s5>06</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE"><s0>Adolescent</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG"><s0>Adolescent</s0>
<s5>07</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA"><s0>Adolescente</s0>
<s5>07</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE"><s0>Résistance traitement</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG"><s0>Treatment resistance</s0>
<s5>08</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA"><s0>Resistencia tratamiento</s0>
<s5>08</s5>
</fC03>
<fC03 i1="09" i2="X" l="FRE"><s0>Tumeur maligne</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="ENG"><s0>Malignant tumor</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="09" i2="X" l="SPA"><s0>Tumor maligno</s0>
<s2>NM</s2>
<s5>09</s5>
</fC03>
<fC03 i1="10" i2="X" l="FRE"><s0>Cancérologie</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="ENG"><s0>Cancerology</s0>
<s5>11</s5>
</fC03>
<fC03 i1="10" i2="X" l="SPA"><s0>Cancerología</s0>
<s5>11</s5>
</fC03>
<fC03 i1="11" i2="X" l="FRE"><s0>Cellule endothéliale</s0>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="ENG"><s0>Endothelial cell</s0>
<s5>12</s5>
</fC03>
<fC03 i1="11" i2="X" l="SPA"><s0>Célula endotelial</s0>
<s5>12</s5>
</fC03>
<fC03 i1="12" i2="X" l="FRE"><s0>Antiinflammatoire non stéroïde</s0>
<s5>23</s5>
</fC03>
<fC03 i1="12" i2="X" l="ENG"><s0>Non steroidal antiinflammatory agent</s0>
<s5>23</s5>
</fC03>
<fC03 i1="12" i2="X" l="SPA"><s0>Antiinflamatorio no esteroide</s0>
<s5>23</s5>
</fC03>
<fC03 i1="13" i2="X" l="FRE"><s0>Gène sis</s0>
<s4>INC</s4>
<s5>86</s5>
</fC03>
<fC03 i1="14" i2="X" l="FRE"><s0>Chimiothérapie métronomique</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="14" i2="X" l="ENG"><s0>Metronomic chemotherapy</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE"><s0>Homme</s0>
</fC07>
<fC07 i1="01" i2="X" l="ENG"><s0>Human</s0>
</fC07>
<fC07 i1="01" i2="X" l="SPA"><s0>Hombre</s0>
</fC07>
<fC07 i1="02" i2="X" l="FRE"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG"><s0>Cancer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA"><s0>Cáncer</s0>
<s2>NM</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE"><s0>Antimitotique</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="ENG"><s0>Antimitotic</s0>
<s5>37</s5>
</fC07>
<fC07 i1="03" i2="X" l="SPA"><s0>Antimitótico</s0>
<s5>37</s5>
</fC07>
<fC07 i1="04" i2="X" l="FRE"><s0>DNA topoisomerase (ATP-hydrolysing)</s0>
<s2>FE</s2>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="ENG"><s0>DNA topoisomerase (ATP-hydrolysing)</s0>
<s2>FE</s2>
<s5>38</s5>
</fC07>
<fC07 i1="04" i2="X" l="SPA"><s0>DNA topoisomerase (ATP-hydrolysing)</s0>
<s2>FE</s2>
<s5>38</s5>
</fC07>
<fC07 i1="05" i2="X" l="FRE"><s0>Isomerases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG"><s0>Isomerases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA"><s0>Isomerases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="ENG"><s0>Enzyme</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="06" i2="X" l="SPA"><s0>Enzima</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="07" i2="X" l="FRE"><s0>Inhibiteur enzyme</s0>
<s5>39</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG"><s0>Enzyme inhibitor</s0>
<s5>39</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA"><s0>Inhibidor enzima</s0>
<s5>39</s5>
</fC07>
<fC07 i1="08" i2="X" l="FRE"><s0>Dérivé de la podophyllotoxine</s0>
<s5>40</s5>
</fC07>
<fC07 i1="08" i2="X" l="ENG"><s0>Podophyllotoxin derivatives</s0>
<s5>40</s5>
</fC07>
<fC07 i1="08" i2="X" l="SPA"><s0>Podofilotoxina derivado</s0>
<s5>40</s5>
</fC07>
<fC07 i1="09" i2="X" l="FRE"><s0>Inhibiteur de la topoisomérase II</s0>
<s5>41</s5>
</fC07>
<fC07 i1="09" i2="X" l="ENG"><s0>Topoisomerase II inhibitor</s0>
<s5>41</s5>
</fC07>
<fC07 i1="09" i2="X" l="SPA"><s0>Inhibidor topoisomerase II</s0>
<s5>41</s5>
</fC07>
<fC07 i1="10" i2="X" l="FRE"><s0>Agent alkylant</s0>
<s5>42</s5>
</fC07>
<fC07 i1="10" i2="X" l="ENG"><s0>Alkylating agent</s0>
<s5>42</s5>
</fC07>
<fC07 i1="10" i2="X" l="SPA"><s0>Agente alquilante</s0>
<s5>42</s5>
</fC07>
<fC07 i1="11" i2="X" l="FRE"><s0>Moutarde à l'azote</s0>
<s5>43</s5>
</fC07>
<fC07 i1="11" i2="X" l="ENG"><s0>Nitrogen mustard</s0>
<s5>43</s5>
</fC07>
<fC07 i1="11" i2="X" l="SPA"><s0>Mostaza al nitrógeno</s0>
<s5>43</s5>
</fC07>
<fC07 i1="12" i2="X" l="FRE"><s0>Dérivé de l'oxazaphosphinane</s0>
<s5>44</s5>
</fC07>
<fC07 i1="12" i2="X" l="ENG"><s0>Oxazaphosphinane derivatives</s0>
<s5>44</s5>
</fC07>
<fC07 i1="12" i2="X" l="SPA"><s0>Oxazafosfinano derivado</s0>
<s5>44</s5>
</fC07>
<fC07 i1="13" i2="X" l="FRE"><s0>Inhibiteur cyclooxygenase 2</s0>
<s5>45</s5>
</fC07>
<fC07 i1="13" i2="X" l="ENG"><s0>Cyclooxygenase 2 inhibitor</s0>
<s5>45</s5>
</fC07>
<fC07 i1="13" i2="X" l="SPA"><s0>Inhibidor cyclooxygenase 2</s0>
<s5>45</s5>
</fC07>
<fC07 i1="14" i2="X" l="FRE"><s0>Prostaglandin-endoperoxide synthase</s0>
<s2>FE</s2>
<s5>46</s5>
</fC07>
<fC07 i1="14" i2="X" l="ENG"><s0>Prostaglandin-endoperoxide synthase</s0>
<s2>FE</s2>
<s5>46</s5>
</fC07>
<fC07 i1="14" i2="X" l="SPA"><s0>Prostaglandin-endoperoxide synthase</s0>
<s2>FE</s2>
<s5>46</s5>
</fC07>
<fC07 i1="15" i2="X" l="FRE"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="15" i2="X" l="ENG"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fC07 i1="15" i2="X" l="SPA"><s0>Oxidoreductases</s0>
<s2>FE</s2>
</fC07>
<fN21><s1>259</s1>
</fN21>
<fN44 i1="01"><s1>OTO</s1>
</fN44>
<fN82><s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<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>
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