Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma
Identifieur interne : 001159 ( Istex/Curation ); précédent : 001158; suivant : 001160Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma
Auteurs : Irene Schmid [Allemagne] ; Beate H Berle [Allemagne] ; Michael H. Albert [Allemagne] ; Selim Corbacioglu [Allemagne] ; Birgit Fröhlich [Allemagne] ; Norbert Graf [Allemagne] ; Birgit Kammer [Allemagne] ; Udo Kontny [Allemagne] ; Ivo Leuschner [Allemagne] ; Hans-Gerhard Scheel-Walter [Allemagne] ; Wolfram Scheurlen [Allemagne] ; Sebastian Werner [Allemagne] ; Thomas Wiesel [Allemagne] ; Dietrich Von Schweinitz [Allemagne]Source :
- 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.
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DOI: 10.1002/pbc.23295
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<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title xml:lang="en">Sorafenib and cisplatin/doxorubicin (PLADO) in pediatric hepatocellular carcinoma</title><author><name sortKey="Schmid, Irene" sort="Schmid, Irene" uniqKey="Schmid I" first="Irene" last="Schmid">Irene Schmid</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University Munich, Lindwurmstr. 4, 80337 Munich, Germany.===</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University Munich, Lindwurmstr. 4, 80337 Munich</wicri:regionArea></affiliation></author><author><name sortKey="H Berle, Beate" sort="H Berle, Beate" uniqKey="H Berle B" first="Beate" last="H Berle">Beate H Berle</name><affiliation wicri:level="1"><mods:affiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich</wicri:regionArea></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 wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich</wicri:regionArea></affiliation></author><author><name sortKey="Corbacioglu, Selim" sort="Corbacioglu, Selim" uniqKey="Corbacioglu S" first="Selim" last="Corbacioglu">Selim Corbacioglu</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg</wicri:regionArea></affiliation></author><author><name sortKey="Frohlich, Birgit" sort="Frohlich, Birgit" uniqKey="Frohlich B" 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wicri:level="1"><mods:affiliation>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich</wicri:regionArea></affiliation></author><author><name sortKey="Kontny, Udo" sort="Kontny, Udo" uniqKey="Kontny U" first="Udo" last="Kontny">Udo Kontny</name><affiliation wicri:level="1"><mods:affiliation>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Leuschner, Ivo" sort="Leuschner, Ivo" uniqKey="Leuschner I" first="Ivo" last="Leuschner">Ivo Leuschner</name><affiliation wicri:level="1"><mods:affiliation>Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig Holstein, Kiel, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig Holstein, Kiel</wicri:regionArea></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 wicri:level="1"><mods:affiliation>Department of Pediatric Hematology/Oncology, University Children's Hospital, Tuebingen, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology/Oncology, University Children's Hospital, Tuebingen</wicri:regionArea></affiliation></author><author><name sortKey="Scheurlen, Wolfram" sort="Scheurlen, Wolfram" uniqKey="Scheurlen W" first="Wolfram" last="Scheurlen">Wolfram Scheurlen</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Oncology, Cnopf‘sche Kinderklinik, Nürnberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Oncology, Cnopf‘sche Kinderklinik, Nürnberg</wicri:regionArea></affiliation></author><author><name sortKey="Werner, Sebastian" sort="Werner, Sebastian" uniqKey="Werner S" first="Sebastian" last="Werner">Sebastian Werner</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen</wicri:regionArea></affiliation></author><author><name sortKey="Wiesel, Thomas" sort="Wiesel, Thomas" 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Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich</wicri:regionArea></affiliation><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University Munich, Lindwurmstr. 4, 80337 Munich, Germany.===</mods:affiliation><country xml:lang="fr" wicri:curation="lc">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University Munich, Lindwurmstr. 4, 80337 Munich</wicri:regionArea></affiliation></author><author><name sortKey="H Berle, Beate" sort="H Berle, Beate" uniqKey="H Berle B" first="Beate" last="H Berle">Beate H Berle</name><affiliation wicri:level="1"><mods:affiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, 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Albert</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich</wicri:regionArea></affiliation></author><author><name sortKey="Corbacioglu, Selim" sort="Corbacioglu, Selim" uniqKey="Corbacioglu S" first="Selim" last="Corbacioglu">Selim Corbacioglu</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, University Hospital, Regensburg</wicri:regionArea></affiliation></author><author><name sortKey="Frohlich, Birgit" sort="Frohlich, Birgit" uniqKey="Frohlich B" first="Birgit" last="Fröhlich">Birgit Fröhlich</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, University Children's Hospital, Muenster</wicri:regionArea></affiliation></author><author><name sortKey="Graf, Norbert" sort="Graf, Norbert" uniqKey="Graf N" first="Norbert" last="Graf">Norbert Graf</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Oncology, University Hospital, Homburg/Saar, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Oncology, University Hospital, Homburg/Saar</wicri:regionArea></affiliation></author><author><name sortKey="Kammer, Birgit" sort="Kammer, Birgit" uniqKey="Kammer B" first="Birgit" last="Kammer">Birgit Kammer</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Radiology, Children's Hospital of the Ludwig‐Maximilians‐University, Munich</wicri:regionArea></affiliation></author><author><name sortKey="Kontny, Udo" sort="Kontny, Udo" uniqKey="Kontny U" first="Udo" last="Kontny">Udo Kontny</name><affiliation wicri:level="1"><mods:affiliation>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, Albert‐Ludwigs‐University, Freiburg</wicri:regionArea></affiliation></author><author><name sortKey="Leuschner, Ivo" sort="Leuschner, Ivo" uniqKey="Leuschner I" first="Ivo" last="Leuschner">Ivo Leuschner</name><affiliation wicri:level="1"><mods:affiliation>Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig Holstein, Kiel, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Kiel Paediatric Tumor Registry, Department of Paediatric Pathology, University Hospital Schleswig Holstein, Kiel</wicri:regionArea></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 wicri:level="1"><mods:affiliation>Department of Pediatric Hematology/Oncology, University Children's Hospital, Tuebingen, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology/Oncology, University Children's Hospital, Tuebingen</wicri:regionArea></affiliation></author><author><name sortKey="Scheurlen, Wolfram" sort="Scheurlen, Wolfram" uniqKey="Scheurlen W" first="Wolfram" last="Scheurlen">Wolfram Scheurlen</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Oncology, Cnopf‘sche Kinderklinik, Nürnberg, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Oncology, Cnopf‘sche Kinderklinik, Nürnberg</wicri:regionArea></affiliation></author><author><name sortKey="Werner, Sebastian" sort="Werner, Sebastian" uniqKey="Werner S" first="Sebastian" last="Werner">Sebastian Werner</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, Justus Liebig University, Giessen</wicri:regionArea></affiliation></author><author><name sortKey="Wiesel, Thomas" sort="Wiesel, Thomas" uniqKey="Wiesel T" first="Thomas" last="Wiesel">Thomas Wiesel</name><affiliation wicri:level="1"><mods:affiliation>Department of Pediatric Hematology and Oncology, University Witten‐Herdecke, Datteln, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Pediatric Hematology and Oncology, University Witten‐Herdecke, Datteln</wicri:regionArea></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 wicri:level="1"><mods:affiliation>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich, Germany</mods:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Pediatric Surgery, Children's Hospital of the Ludwig‐Maximilians‐University, Munich</wicri:regionArea></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></record>Pour manipuler ce document sous Unix (Dilib)
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