Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma
Identifieur interne : 001248 ( Istex/Corpus ); précédent : 001247; suivant : 001249Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma
Auteurs : Irene Schmid ; Beate H Berle ; Michael H. Albert ; Selim Corbacioglu ; Birgit Fröhlich ; Norbert Graf ; Birgit Kammer ; Udo Kontny ; Ivo Leuschner ; Hans-Gerhard Scheel-Walter ; Wolfram Scheurlen ; Sebastian Werner ; Thomas Wiesel ; Dietrich Von SchweinitzSource :
- Pediatric Blood & Cancer [ 1545-5009 ] ; 2012-04.
English descriptors
- KwdEn :
- Teeft :
- Adult patients, Carcinoma, Chemotherapy, Cisplatin, Clin oncol, Combination therapy, Complete remission, Complete resection, Diff, Doxorubicin, Hematology, Hepatocellular, Hepatocellular carcinoma, Hfsr, Hfsr grade, Imaging modalities, Imaging studies, Important toxicity, International society, Liver transplantation, Local relapse, Median, Metastatic, Metastatic disease, Multifocal, Oncol, Oncology, Partial response, Pediatr, Pediatr blood cancer, Pediatr oncol, Pediatric, Pediatric hematology, Pediatric liver tumor group, Pediatric oncology, Pediatric patients, Plado, Portal vein, Preoperative chemotherapy, Pretreatment extent, Primary unresectable tumor, Progressive disease, Recist criteria, Relapse, Resectable, Resection, Skin reaction, Sorafenib, Stable disease, Toxicity, Transplantation, Tumor progression, Tumor response, Unique patient number, University hospital, Unresectable, Unresectable tumor.
Abstract
Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression‐free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m2/day, doxorubicin 2 × 30 mg/m2/day) in combination with sorafenib in pediatric HCC patients.
Clinical data of 12 patients (7–16 years), 7 with unresectable tumor, were retrospectively assessed.
In total 6/12 (50%) patients are in complete remission after a median follow‐up of 20 months (4 with PLADO/sorafenib/resection, 2 with liver transplantation after local relapse). Of the seven patients with unresectable tumor, PLADO/sorafenib resulted in partial response (PR) in four, stable disease (SD) in two, and progression in one. Three are alive in CR after complete resection after 12 (alternative therapy after two cycles PLADO/sorafenib), 12 and 18 months (six cycles PLADO/sorafenib), respectively. All four patients with elevated alpha‐fetoprotein levels had a marked drop after two cycles. Of the five patients with primary complete tumor resection one is alive disease‐free at 27 months. Four had local or metastatic relapses (13, 7, 12, and 13 months), two of whom were rescued by liver transplantation (CR after 25 and 32 months). The main toxicity attributable to sorafenib was a hand–foot skin reaction (HFSR) in seven patients.
Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib. Pediatr Blood Cancer 2012; 58: 539–544. © 2011 Wiley Periodicals, Inc.
Url:
DOI: 10.1002/pbc.23295
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ISTEX:B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39Le document en format XML
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sortKey="H Berle, Beate" sort="H Berle, Beate" uniqKey="H Berle B" first="Beate" last="H Berle">Beate H Berle</name><affiliation><mods:affiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Albert, Michael H" sort="Albert, Michael H" uniqKey="Albert M" first="Michael H." last="Albert">Michael H. Albert</name><affiliation><mods:affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Corbacioglu, Selim" sort="Corbacioglu, Selim" uniqKey="Corbacioglu S" first="Selim" last="Corbacioglu">Selim Corbacioglu</name><affiliation><mods:affiliation>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Frohlich, Birgit" sort="Frohlich, Birgit" uniqKey="Frohlich B" first="Birgit" last="Fröhlich">Birgit Fröhlich</name><affiliation><mods:affiliation>Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany</mods:affiliation></affiliation></author><author><name sortKey="Graf, Norbert" sort="Graf, Norbert" uniqKey="Graf N" first="Norbert" last="Graf">Norbert Graf</name><affiliation><mods:affiliation>Department of Pediatric Oncology, University Hospital, Homburg/Saar, Germany</mods:affiliation></affiliation></author><author><name sortKey="Kammer, Birgit" sort="Kammer, Birgit" uniqKey="Kammer B" first="Birgit" last="Kammer">Birgit Kammer</name><affiliation><mods:affiliation>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation></affiliation></author><author><name sortKey="Kontny, Udo" sort="Kontny, Udo" uniqKey="Kontny U" first="Udo" last="Kontny">Udo Kontny</name><affiliation><mods:affiliation>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Leuschner, Ivo" sort="Leuschner, Ivo" uniqKey="Leuschner I" first="Ivo" last="Leuschner">Ivo Leuschner</name><affiliation><mods:affiliation>Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig Holstein, Kiel, Germany</mods:affiliation></affiliation></author><author><name sortKey="Scheel Alter, Hans Erhard" sort="Scheel Alter, Hans Erhard" uniqKey="Scheel Alter H" first="Hans-Gerhard" last="Scheel-Walter">Hans-Gerhard Scheel-Walter</name><affiliation><mods:affiliation>Department of Pediatric Hematology/Oncology, University Children's Hospital, Tuebingen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Scheurlen, Wolfram" sort="Scheurlen, Wolfram" uniqKey="Scheurlen W" first="Wolfram" last="Scheurlen">Wolfram Scheurlen</name><affiliation><mods:affiliation>Department of Pediatric Oncology, Cnopf‘sche Kinderklinik, Nürnberg, Germany</mods:affiliation></affiliation></author><author><name sortKey="Werner, Sebastian" sort="Werner, Sebastian" uniqKey="Werner S" first="Sebastian" last="Werner">Sebastian Werner</name><affiliation><mods:affiliation>Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany</mods:affiliation></affiliation></author><author><name sortKey="Wiesel, Thomas" sort="Wiesel, Thomas" uniqKey="Wiesel T" first="Thomas" last="Wiesel">Thomas Wiesel</name><affiliation><mods:affiliation>Department of Pediatric Hematology and Oncology, University Witten‐Herdecke, Datteln, Germany</mods:affiliation></affiliation></author><author><name sortKey="Von Schweinitz, Dietrich" sort="Von Schweinitz, Dietrich" uniqKey="Von Schweinitz D" first="Dietrich" last="Von Schweinitz">Dietrich Von Schweinitz</name><affiliation><mods:affiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation></affiliation></author></analytic><monogr></monogr><series><title level="j">Pediatric Blood & Cancer</title><title level="j" type="abbrev">Pediatr. Blood Cancer</title><idno type="ISSN">1545-5009</idno><idno type="eISSN">1545-5017</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2012-04">2012-04</date><biblScope unit="volume">58</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="539">539</biblScope><biblScope unit="page" to="544">544</biblScope></imprint><idno type="ISSN">1545-5009</idno></series><idno type="istex">B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39</idno><idno type="DOI">10.1002/pbc.23295</idno><idno type="ArticleID">PBC23295</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">1545-5009</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>PLADO</term><term>cisplatin</term><term>doxorubicin</term><term>hepatocellular carcinoma</term><term>pediatric</term><term>sorafenib</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Adult patients</term><term>Carcinoma</term><term>Chemotherapy</term><term>Cisplatin</term><term>Clin oncol</term><term>Combination therapy</term><term>Complete remission</term><term>Complete resection</term><term>Diff</term><term>Doxorubicin</term><term>Hematology</term><term>Hepatocellular</term><term>Hepatocellular carcinoma</term><term>Hfsr</term><term>Hfsr grade</term><term>Imaging modalities</term><term>Imaging studies</term><term>Important toxicity</term><term>International society</term><term>Liver transplantation</term><term>Local relapse</term><term>Median</term><term>Metastatic</term><term>Metastatic disease</term><term>Multifocal</term><term>Oncol</term><term>Oncology</term><term>Partial response</term><term>Pediatr</term><term>Pediatr blood cancer</term><term>Pediatr oncol</term><term>Pediatric</term><term>Pediatric hematology</term><term>Pediatric liver tumor group</term><term>Pediatric oncology</term><term>Pediatric patients</term><term>Plado</term><term>Portal vein</term><term>Preoperative chemotherapy</term><term>Pretreatment extent</term><term>Primary unresectable tumor</term><term>Progressive disease</term><term>Recist criteria</term><term>Relapse</term><term>Resectable</term><term>Resection</term><term>Skin reaction</term><term>Sorafenib</term><term>Stable disease</term><term>Toxicity</term><term>Transplantation</term><term>Tumor progression</term><term>Tumor response</term><term>Unique patient number</term><term>University hospital</term><term>Unresectable</term><term>Unresectable tumor</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression‐free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m2/day, doxorubicin 2 × 30 mg/m2/day) in combination with sorafenib in pediatric HCC patients.</div><div type="abstract">Clinical data of 12 patients (7–16 years), 7 with unresectable tumor, were retrospectively assessed.</div><div type="abstract">In total 6/12 (50%) patients are in complete remission after a median follow‐up of 20 months (4 with PLADO/sorafenib/resection, 2 with liver transplantation after local relapse). Of the seven patients with unresectable tumor, PLADO/sorafenib resulted in partial response (PR) in four, stable disease (SD) in two, and progression in one. Three are alive in CR after complete resection after 12 (alternative therapy after two cycles PLADO/sorafenib), 12 and 18 months (six cycles PLADO/sorafenib), respectively. All four patients with elevated alpha‐fetoprotein levels had a marked drop after two cycles. Of the five patients with primary complete tumor resection one is alive disease‐free at 27 months. Four had local or metastatic relapses (13, 7, 12, and 13 months), two of whom were rescued by liver transplantation (CR after 25 and 32 months). The main toxicity attributable to sorafenib was a hand–foot skin reaction (HFSR) in seven patients.</div><div type="abstract">Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib. Pediatr Blood Cancer 2012; 58: 539–544. © 2011 Wiley Periodicals, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>sorafenib</json:string><json:string>pediatric</json:string><json:string>resection</json:string><json:string>plado</json:string><json:string>toxicity</json:string><json:string>hfsr</json:string><json:string>oncology</json:string><json:string>unresectable</json:string><json:string>chemotherapy</json:string><json:string>doxorubicin</json:string><json:string>hepatocellular</json:string><json:string>pediatr</json:string><json:string>relapse</json:string><json:string>hepatocellular carcinoma</json:string><json:string>metastatic</json:string><json:string>oncol</json:string><json:string>transplantation</json:string><json:string>diff</json:string><json:string>multifocal</json:string><json:string>cisplatin</json:string><json:string>hematology</json:string><json:string>carcinoma</json:string><json:string>complete resection</json:string><json:string>progressive disease</json:string><json:string>resectable</json:string><json:string>pediatric hematology</json:string><json:string>hfsr grade</json:string><json:string>adult patients</json:string><json:string>tumor response</json:string><json:string>pediatric liver tumor group</json:string><json:string>liver transplantation</json:string><json:string>unresectable tumor</json:string><json:string>complete remission</json:string><json:string>international society</json:string><json:string>preoperative chemotherapy</json:string><json:string>clin oncol</json:string><json:string>tumor progression</json:string><json:string>pediatr blood cancer</json:string><json:string>pretreatment extent</json:string><json:string>imaging modalities</json:string><json:string>portal vein</json:string><json:string>pediatric oncology</json:string><json:string>primary unresectable tumor</json:string><json:string>skin reaction</json:string><json:string>partial response</json:string><json:string>stable disease</json:string><json:string>median</json:string><json:string>important toxicity</json:string><json:string>imaging studies</json:string><json:string>recist criteria</json:string><json:string>unique patient number</json:string><json:string>pediatric patients</json:string><json:string>metastatic disease</json:string><json:string>combination therapy</json:string><json:string>local relapse</json:string><json:string>university hospital</json:string><json:string>pediatr oncol</json:string></teeft></keywords><author><json:item><name>Irene Schmid MD</name><affiliations><json:string>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</json:string><json:string>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University Munich, Lindwurmstr. 4, 80337 Munich, Germany.===</json:string></affiliations></json:item><json:item><name>Beate Häberle MD</name><affiliations><json:string>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</json:string></affiliations></json:item><json:item><name>Michael H. Albert MD</name><affiliations><json:string>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</json:string></affiliations></json:item><json:item><name>Selim Corbacioglu MD</name><affiliations><json:string>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany</json:string></affiliations></json:item><json:item><name>Birgit Fröhlich MD</name><affiliations><json:string>Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany</json:string></affiliations></json:item><json:item><name>Norbert Graf MD</name><affiliations><json:string>Department of Pediatric Oncology, University Hospital, Homburg/Saar, Germany</json:string></affiliations></json:item><json:item><name>Birgit Kammer MD</name><affiliations><json:string>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</json:string></affiliations></json:item><json:item><name>Udo Kontny MD</name><affiliations><json:string>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg, Germany</json:string></affiliations></json:item><json:item><name>Ivo Leuschner MD</name><affiliations><json:string>Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig Holstein, Kiel, Germany</json:string></affiliations></json:item><json:item><name>Hans‐Gerhard Scheel‐Walter MD</name><affiliations><json:string>Department of Pediatric Hematology/Oncology, University Children's Hospital, Tuebingen, Germany</json:string></affiliations></json:item><json:item><name>Wolfram Scheurlen MD</name><affiliations><json:string>Department of Pediatric Oncology, Cnopf‘sche Kinderklinik, Nürnberg, Germany</json:string></affiliations></json:item><json:item><name>Sebastian Werner MD</name><affiliations><json:string>Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany</json:string></affiliations></json:item><json:item><name>Thomas Wiesel MD</name><affiliations><json:string>Department of Pediatric Hematology and Oncology, University Witten‐Herdecke, Datteln, Germany</json:string></affiliations></json:item><json:item><name>Dietrich von Schweinitz MD</name><affiliations><json:string>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>cisplatin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>doxorubicin</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>hepatocellular 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Article</value></json:item></subject></host><publicationDate>2012</publicationDate><copyrightDate>2012</copyrightDate><doi><json:string>10.1002/pbc.23295</json:string></doi><id>B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39</id><score>1</score><fulltext><json:item><extension>pdf</extension><original>true</original><mimetype>application/pdf</mimetype><uri>https://api.istex.fr/document/B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39/fulltext/pdf</uri></json:item><json:item><extension>zip</extension><original>false</original><mimetype>application/zip</mimetype><uri>https://api.istex.fr/document/B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39/fulltext/zip</uri></json:item><istex:fulltextTEI uri="https://api.istex.fr/document/B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39/fulltext/tei"><teiHeader><fileDesc><titleStmt><title level="a" type="main" xml:lang="en">Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma</title></titleStmt><publicationStmt><authority>ISTEX</authority><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><availability><p>Copyright © 2011 Wiley Periodicals, Inc.</p></availability><date>2012</date></publicationStmt><notesStmt><note type="content">*Presented in part at the 41st Annual Conference of the International Society of Paediatric Oncology (SIOP), Sao Paulo, Brazil, October 5–9, 2009.</note><note type="content">*Conflict of interest: Nothing to declare.</note></notesStmt><sourceDesc><biblStruct type="inbook"><analytic><title level="a" type="main" xml:lang="en">Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma</title><author xml:id="author-1"><persName><forename type="first">Irene</forename><surname>Schmid</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation><affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University Munich, Lindwurmstr. 4, 80337 Munich, Germany.===</affiliation></author><author xml:id="author-2"><persName><forename type="first">Beate</forename><surname>Häberle</surname></persName><roleName type="degree">MD</roleName><affiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation></author><author xml:id="author-3"><persName><forename type="first">Michael H.</forename><surname>Albert</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation></author><author xml:id="author-4"><persName><forename type="first">Selim</forename><surname>Corbacioglu</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany</affiliation></author><author xml:id="author-5"><persName><forename type="first">Birgit</forename><surname>Fröhlich</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany</affiliation></author><author xml:id="author-6"><persName><forename type="first">Norbert</forename><surname>Graf</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Oncology, University Hospital, Homburg/Saar, Germany</affiliation></author><author xml:id="author-7"><persName><forename type="first">Birgit</forename><surname>Kammer</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation></author><author xml:id="author-8"><persName><forename type="first">Udo</forename><surname>Kontny</surname></persName><roleName type="degree">MD</roleName><affiliation>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg, Germany</affiliation></author><author xml:id="author-9"><persName><forename type="first">Ivo</forename><surname>Leuschner</surname></persName><roleName type="degree">MD</roleName><affiliation>Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig Holstein, Kiel, Germany</affiliation></author><author xml:id="author-10"><persName><forename type="first">Hans‐Gerhard</forename><surname>Scheel‐Walter</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Hematology/Oncology, University Children's Hospital, Tuebingen, Germany</affiliation></author><author xml:id="author-11"><persName><forename type="first">Wolfram</forename><surname>Scheurlen</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Oncology, Cnopf‘sche Kinderklinik, Nürnberg, Germany</affiliation></author><author xml:id="author-12"><persName><forename type="first">Sebastian</forename><surname>Werner</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany</affiliation></author><author xml:id="author-13"><persName><forename type="first">Thomas</forename><surname>Wiesel</surname></persName><roleName type="degree">MD</roleName><affiliation>Department of Pediatric Hematology and Oncology, University Witten‐Herdecke, Datteln, Germany</affiliation></author><author xml:id="author-14"><persName><forename type="first">Dietrich</forename><surname>von Schweinitz</surname></persName><roleName type="degree">MD</roleName><affiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation></author></analytic><monogr><title level="j">Pediatric Blood & Cancer</title><title level="j" type="abbrev">Pediatr. Blood Cancer</title><idno type="pISSN">1545-5009</idno><idno type="eISSN">1545-5017</idno><idno type="DOI">10.1002/(ISSN)1545-5017</idno><imprint><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2012-04"></date><biblScope unit="volume">58</biblScope><biblScope unit="issue">4</biblScope><biblScope unit="page" from="539">539</biblScope><biblScope unit="page" to="544">544</biblScope></imprint></monogr><idno type="istex">B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39</idno><idno type="DOI">10.1002/pbc.23295</idno><idno type="ArticleID">PBC23295</idno></biblStruct></sourceDesc></fileDesc><profileDesc><creation><date>2012</date></creation><langUsage><language ident="en">en</language></langUsage><abstract><p>Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression‐free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m2/day, doxorubicin 2 × 30 mg/m2/day) in combination with sorafenib in pediatric HCC patients.</p></abstract><abstract><p>Clinical data of 12 patients (7–16 years), 7 with unresectable tumor, were retrospectively assessed.</p></abstract><abstract><p>In total 6/12 (50%) patients are in complete remission after a median follow‐up of 20 months (4 with PLADO/sorafenib/resection, 2 with liver transplantation after local relapse). Of the seven patients with unresectable tumor, PLADO/sorafenib resulted in partial response (PR) in four, stable disease (SD) in two, and progression in one. Three are alive in CR after complete resection after 12 (alternative therapy after two cycles PLADO/sorafenib), 12 and 18 months (six cycles PLADO/sorafenib), respectively. All four patients with elevated alpha‐fetoprotein levels had a marked drop after two cycles. Of the five patients with primary complete tumor resection one is alive disease‐free at 27 months. Four had local or metastatic relapses (13, 7, 12, and 13 months), two of whom were rescued by liver transplantation (CR after 25 and 32 months). The main toxicity attributable to sorafenib was a hand–foot skin reaction (HFSR) in seven patients.</p></abstract><abstract><p>Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib. Pediatr Blood Cancer 2012; 58: 539–544. © 2011 Wiley Periodicals, Inc.</p></abstract><textClass xml:lang="en"><keywords scheme="keyword"><list><head>keywords</head><item><term>cisplatin</term></item><item><term>doxorubicin</term></item><item><term>hepatocellular carcinoma</term></item><item><term>pediatric</term></item><item><term>PLADO</term></item><item><term>sorafenib</term></item></list></keywords></textClass><textClass><keywords scheme="Journal Subject"><list><head>article-category</head><item><term>Research Article</term></item></list></keywords></textClass></profileDesc><revisionDesc><change when="2011-01-30">Received</change><change when="2011-07-06">Registration</change><change when="2012-04">Published</change></revisionDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" encoding="UTF-8" standalone="yes"</istex:xmlDeclaration><istex:document><component version="2.0" type="serialArticle" xml:lang="en"><header><publicationMeta level="product"><publisherInfo><publisherName>Wiley Subscription Services, Inc., A Wiley Company</publisherName><publisherLoc>Hoboken</publisherLoc></publisherInfo><doi registered="yes">10.1002/(ISSN)1545-5017</doi><issn type="print">1545-5009</issn><issn type="electronic">1545-5017</issn><idGroup><id type="product" value="PBC"></id></idGroup><titleGroup><title type="main" xml:lang="en" sort="PEDIATRIC BLOOD AND CANCER">Pediatric Blood & Cancer</title><title type="short">Pediatr. Blood Cancer</title></titleGroup><selfCitationGroup><citation type="ancestor" xml:id="cit1"><journalTitle>Medical and Pediatric Oncology</journalTitle><accessionId ref="info:x-wiley/issn/00960802">0096-0802</accessionId><accessionId ref="info:x-wiley/issn/1096911X">1096-911X</accessionId><pubYear year="2003">2003</pubYear><vol>41</vol><issue>6</issue></citation></selfCitationGroup></publicationMeta><publicationMeta level="part" position="40"><doi origin="wiley" registered="yes">10.1002/pbc.v58.4</doi><numberingGroup><numbering type="journalVolume" number="58">58</numbering><numbering type="journalIssue">4</numbering></numberingGroup><coverDate startDate="2012-04">April 2012</coverDate></publicationMeta><publicationMeta level="unit" type="article" position="120" status="forIssue"><doi origin="wiley" registered="yes">10.1002/pbc.23295</doi><idGroup><id type="unit" value="PBC23295"></id></idGroup><countGroup><count type="pageTotal" number="6"></count></countGroup><titleGroup><title 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type="pageLast">544</numbering></numberingGroup><correspondenceTo>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University Munich, Lindwurmstr. 4, 80337 Munich, Germany.===</correspondenceTo><linkGroup><link type="toTypesetVersion" href="file:PBC.PBC23295.pdf"></link></linkGroup></publicationMeta><contentMeta><countGroup><count type="figureTotal" number="0"></count><count type="tableTotal" number="3"></count><count type="referenceTotal" number="24"></count><count type="wordTotal" number="5296"></count></countGroup><titleGroup><title type="main" xml:lang="en">Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma<link href="#fn1"></link><link href="#fn2"></link></title><title type="short" xml:lang="en">PLADO/Sorafenib in Pediatric HCC</title></titleGroup><creators><creator xml:id="au1" creatorRole="author" affiliationRef="#af1" corresponding="yes"><personName><givenNames>Irene</givenNames><familyName>Schmid</familyName><degrees>MD</degrees></personName><contactDetails><email normalForm="irene.schmid@med.uni-muenchen.de">irene.schmid@med.uni‐muenchen.de</email></contactDetails></creator><creator xml:id="au2" creatorRole="author" affiliationRef="#af2"><personName><givenNames>Beate</givenNames><familyName>Häberle</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au3" creatorRole="author" affiliationRef="#af1"><personName><givenNames>Michael H.</givenNames><familyName>Albert</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au4" creatorRole="author" affiliationRef="#af3"><personName><givenNames>Selim</givenNames><familyName>Corbacioglu</familyName><degrees>MD</degrees></personName></creator><creator xml:id="au5" creatorRole="author" 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type="organization"><unparsedAffiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af2" countryCode="DE" type="organization"><unparsedAffiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af3" countryCode="DE" type="organization"><unparsedAffiliation>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af4" countryCode="DE" type="organization"><unparsedAffiliation>Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af5" countryCode="DE" type="organization"><unparsedAffiliation>Department of Pediatric Oncology, University Hospital, Homburg/Saar, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af6" countryCode="DE" type="organization"><unparsedAffiliation>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af7" countryCode="DE" type="organization"><unparsedAffiliation>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af8" countryCode="DE" type="organization"><unparsedAffiliation>Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig Holstein, Kiel, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af9" countryCode="DE" type="organization"><unparsedAffiliation>Department of Pediatric Hematology/Oncology, University Children's Hospital, Tuebingen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af10" countryCode="DE" type="organization"><unparsedAffiliation>Department of Pediatric Oncology, Cnopf‘sche Kinderklinik, Nürnberg, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af11" countryCode="DE" type="organization"><unparsedAffiliation>Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany</unparsedAffiliation></affiliation><affiliation xml:id="af12" countryCode="DE" type="organization"><unparsedAffiliation>Department of Pediatric Hematology and Oncology, University Witten‐Herdecke, Datteln, Germany</unparsedAffiliation></affiliation></affiliationGroup><keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">cisplatin</keyword><keyword xml:id="kwd2">doxorubicin</keyword><keyword xml:id="kwd3">hepatocellular carcinoma</keyword><keyword xml:id="kwd4">pediatric</keyword><keyword xml:id="kwd5">PLADO</keyword><keyword xml:id="kwd6">sorafenib</keyword></keywordGroup><abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title><section xml:id="abs1-1"><title type="main">Purpose</title><p>Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression‐free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m<sup>2</sup>/day, doxorubicin 2 × 30 mg/m<sup>2</sup>/day) in combination with sorafenib in pediatric HCC patients.</p></section><section xml:id="abs1-2"><title type="main">Patients and Methods</title><p>Clinical data of 12 patients (7–16 years), 7 with unresectable tumor, were retrospectively assessed.</p></section><section xml:id="abs1-3"><title type="main">Results</title><p>In total 6/12 (50%) patients are in complete remission after a median follow‐up of 20 months (4 with PLADO/sorafenib/resection, 2 with liver transplantation after local relapse). Of the seven patients with unresectable tumor, PLADO/sorafenib resulted in partial response (PR) in four, stable disease (SD) in two, and progression in one. Three are alive in CR after complete resection after 12 (alternative therapy after two cycles PLADO/sorafenib), 12 and 18 months (six cycles PLADO/sorafenib), respectively. All four patients with elevated alpha‐fetoprotein levels had a marked drop after two cycles. Of the five patients with primary complete tumor resection one is alive disease‐free at 27 months. Four had local or metastatic relapses (13, 7, 12, and 13 months), two of whom were rescued by liver transplantation (CR after 25 and 32 months). The main toxicity attributable to sorafenib was a hand–foot skin reaction (HFSR) in seven patients.</p></section><section xml:id="abs1-4"><title type="main">Conclusion</title><p>Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib. Pediatr Blood Cancer 2012; 58: 539–544. © 2011 Wiley Periodicals, Inc.</p></section></abstract></abstractGroup></contentMeta><noteGroup><note xml:id="fn1"><p>Presented in part at the 41st Annual Conference of the International Society of Paediatric Oncology (SIOP), Sao Paulo, Brazil, October 5–9, 2009.</p></note><note xml:id="fn2"><p>Conflict of interest: Nothing to declare.</p></note></noteGroup></header></component></istex:document></istex:metadataXml><mods version="3.6"><titleInfo lang="en"><title>Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma</title></titleInfo><titleInfo type="abbreviated" lang="en"><title>PLADO/Sorafenib in Pediatric HCC</title></titleInfo><titleInfo type="alternative" contentType="CDATA" lang="en"><title>Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma</title></titleInfo><name type="personal"><namePart type="given">Irene</namePart><namePart type="family">Schmid</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation><affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University Munich, Lindwurmstr. 4, 80337 Munich, Germany.===</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Beate</namePart><namePart type="family">Häberle</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Michael H.</namePart><namePart type="family">Albert</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Selim</namePart><namePart type="family">Corbacioglu</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Birgit</namePart><namePart type="family">Fröhlich</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Norbert</namePart><namePart type="family">Graf</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatric Oncology, University Hospital, Homburg/Saar, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Birgit</namePart><namePart type="family">Kammer</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Udo</namePart><namePart type="family">Kontny</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg, Germany</affiliation><role><roleTerm type="text">author</roleTerm></role></name><name type="personal"><namePart type="given">Ivo</namePart><namePart type="family">Leuschner</namePart><namePart type="termsOfAddress">MD</namePart><affiliation>Kiel Paediatric Tumor Registry, 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Company</publisher><place><placeTerm type="text">Hoboken</placeTerm></place><dateIssued encoding="w3cdtf">2012-04</dateIssued><dateCaptured encoding="w3cdtf">2011-01-30</dateCaptured><dateValid encoding="w3cdtf">2011-07-06</dateValid><copyrightDate encoding="w3cdtf">2012</copyrightDate></originInfo><language><languageTerm type="code" authority="rfc3066">en</languageTerm><languageTerm type="code" authority="iso639-2b">eng</languageTerm></language><physicalDescription><internetMediaType>text/html</internetMediaType><extent unit="tables">3</extent><extent unit="references">24</extent><extent unit="words">5296</extent></physicalDescription><abstract>Overall survival is poor in children with primary unresectable hepatocellular carcinoma. Sorafenib has been shown to significantly improve progression‐free survival in adult hepatocellular carcinoma (HCC) patients. We evaluated the experience of PLADO (cisplatin 80 mg/m2/day, doxorubicin 2 × 30 mg/m2/day) in combination with sorafenib in pediatric HCC patients.</abstract><abstract>Clinical data of 12 patients (7–16 years), 7 with unresectable tumor, were retrospectively assessed.</abstract><abstract>In total 6/12 (50%) patients are in complete remission after a median follow‐up of 20 months (4 with PLADO/sorafenib/resection, 2 with liver transplantation after local relapse). Of the seven patients with unresectable tumor, PLADO/sorafenib resulted in partial response (PR) in four, stable disease (SD) in two, and progression in one. Three are alive in CR after complete resection after 12 (alternative therapy after two cycles PLADO/sorafenib), 12 and 18 months (six cycles PLADO/sorafenib), respectively. All four patients with elevated alpha‐fetoprotein levels had a marked drop after two cycles. Of the five patients with primary complete tumor resection one is alive disease‐free at 27 months. Four had local or metastatic relapses (13, 7, 12, and 13 months), two of whom were rescued by liver transplantation (CR after 25 and 32 months). The main toxicity attributable to sorafenib was a hand–foot skin reaction (HFSR) in seven patients.</abstract><abstract>Sorafenib in combination with PLADO may be a promising approach in pediatric HCC; HFSR was the most important toxicity. Data based on prospective studies are needed to evaluate pharmacokinetics, resectability rates, and survival in pediatric HCC treated with sorafenib. Pediatr Blood Cancer 2012; 58: 539–544. © 2011 Wiley Periodicals, Inc.</abstract><note type="content">*Presented in part at the 41st Annual Conference of the International Society of Paediatric Oncology (SIOP), Sao Paulo, Brazil, October 5–9, 2009.</note><note type="content">*Conflict of interest: Nothing to declare.</note><subject lang="en"><genre>keywords</genre><topic>cisplatin</topic><topic>doxorubicin</topic><topic>hepatocellular carcinoma</topic><topic>pediatric</topic><topic>PLADO</topic><topic>sorafenib</topic></subject><relatedItem type="host"><titleInfo><title>Pediatric Blood & Cancer</title></titleInfo><titleInfo type="abbreviated"><title>Pediatr. Blood Cancer</title></titleInfo><genre type="journal">journal</genre><subject><genre>article-category</genre><topic>Research Article</topic></subject><identifier type="ISSN">1545-5009</identifier><identifier type="eISSN">1545-5017</identifier><identifier type="DOI">10.1002/(ISSN)1545-5017</identifier><identifier type="PublisherID">PBC</identifier><part><date>2012</date><detail type="volume"><caption>vol.</caption><number>58</number></detail><detail type="issue"><caption>no.</caption><number>4</number></detail><extent unit="pages"><start>539</start><end>544</end><total>6</total></extent></part></relatedItem><relatedItem type="preceding"><titleInfo><title>Medical and Pediatric Oncology</title></titleInfo><identifier type="ISSN">0096-0802</identifier><identifier type="ISSN">1096-911X</identifier><part><date point="end">2003</date><detail type="volume"><caption>last vol.</caption><number>41</number></detail><detail type="issue"><caption>last no.</caption><number>6</number></detail></part></relatedItem><identifier type="istex">B1DB2E9C22FA7E49F711EDDE6F5A1E3BA0F9FE39</identifier><identifier type="DOI">10.1002/pbc.23295</identifier><identifier type="ArticleID">PBC23295</identifier><accessCondition type="use and reproduction" contentType="copyright">Copyright © 2011 Wiley Periodicals, Inc.</accessCondition><recordInfo><recordContentSource>WILEY</recordContentSource><recordOrigin>Wiley Subscription Services, Inc., A Wiley Company</recordOrigin></recordInfo></mods></metadata><serie></serie></istex></record>Pour manipuler ce document sous Unix (Dilib)
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