Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma
Identifieur interne : 012B42 ( Main/Repository ); précédent : 012B41; suivant : 012B43Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma
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Abstract
Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of 90Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received 111In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8) on day 0 followed by a therapeutic dose of 90Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of 111In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T1/2, blood AUC, plasma T1/2. and plasma AUC. It is concluded that 90Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T1/2, reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population.
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Phase I/II <sup>90</sup>Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma</title><author><name sortKey="Wiseman, G A" uniqKey="Wiseman G">G. A. Wiseman</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Radiology, Nuclear Medicine, Mayo Clinic and Mayo Foundation</s1><s2>Rochester, Minn.</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester, Minn.</wicri:noRegion></affiliation></author><author><name sortKey="White, C A" uniqKey="White C">C. A. White</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IDEC Pharmaceuticals Corp.</s1><s2>San Diego, Calif.</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Idaho</region></placeName></affiliation></author><author><name sortKey="Stabin, M" uniqKey="Stabin M">M. Stabin</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Radiology, Nuclear Medicine, Mayo Clinic and Mayo Foundation</s1><s2>Rochester, Minn.</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester, Minn.</wicri:noRegion></affiliation></author><author><name sortKey="Dunn, W L" uniqKey="Dunn W">W. L. Dunn</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Radiology, Nuclear Medicine, Mayo Clinic and Mayo Foundation</s1><s2>Rochester, Minn.</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester, Minn.</wicri:noRegion></affiliation></author><author><name sortKey="Erwin, W" uniqKey="Erwin W">W. Erwin</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Hematology/Oncology, Department of Medicine, Northwestern University and Robert H. Lurie Comprehensive Cancer Center</s1><s2>Chicago, Ill.</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chicago, Ill.</wicri:noRegion></affiliation></author><author><name sortKey="Dahlbom, M" uniqKey="Dahlbom M">M. Dahlbom</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>University of California at Los Angeles</s1><s2>Los Angeles, Calif.</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>University of California at Los Angeles</wicri:noRegion></affiliation></author><author><name sortKey="Raubitschek, A" uniqKey="Raubitschek A">A. Raubitschek</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>City of Hope</s1><s2>Duarte, Calif.</s2><s3>USA</s3><sZ>7 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>City of Hope</wicri:noRegion></affiliation></author><author><name sortKey="Karvelis, K" uniqKey="Karvelis K">K. Karvelis</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Henry Ford Hospital</s1><s2>Detroit, Mich.</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Henry Ford Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Schultheiss, T" uniqKey="Schultheiss T">T. Schultheiss</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Fox Chase Cancer Center</s1><s2>Philadelphia, Pa.</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Fox Chase Cancer Center</wicri:noRegion></affiliation></author><author><name sortKey="Witzig, T E" uniqKey="Witzig T">T. E. Witzig</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Department of Internal Medicine Division of Hematology, Mayo Clinic and Mayo Foundation</s1><s2>Rochester, Minn.</s2><s3>USA</s3><sZ>10 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Rochester, Minn.</wicri:noRegion></affiliation></author><author><name sortKey="Belanger, R" uniqKey="Belanger R">R. Belanger</name><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Ryan Belanger Associates</s1><s2>San Diego, Calif.</s2><s3>USA</s3><sZ>11 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Ryan Belanger Associates</wicri:noRegion></affiliation></author><author><name sortKey="Spies, S" uniqKey="Spies S">S. Spies</name><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Division of Hematology/Oncology, Department of Medicine, Northwestern University and Robert H. Lurie Comprehensive Cancer Center</s1><s2>Chicago, Ill.</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>12 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>Chicago, Ill.</wicri:noRegion></affiliation></author><author><name sortKey="Silverman, D H S" uniqKey="Silverman D">D. H. S. Silverman</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>University of California at Los Angeles</s1><s2>Los Angeles, Calif.</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>13 aut.</sZ></inist:fA14><country>États-Unis</country><wicri:noRegion>University of California at Los Angeles</wicri:noRegion></affiliation></author><author><name sortKey="Berlfein, J R" uniqKey="Berlfein J">J. R. Berlfein</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IDEC Pharmaceuticals Corp.</s1><s2>San Diego, Calif.</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Idaho</region></placeName></affiliation></author><author><name sortKey="Ding, E" uniqKey="Ding E">E. Ding</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IDEC Pharmaceuticals Corp.</s1><s2>San Diego, Calif.</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Idaho</region></placeName></affiliation></author><author><name sortKey="Grillo Lopez, A J" uniqKey="Grillo Lopez A">A. J. Grillo-Lopez</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>IDEC Pharmaceuticals Corp.</s1><s2>San Diego, Calif.</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Idaho</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="inist">00-0372632</idno><date when="2000">2000</date><idno type="stanalyst">PASCAL 00-0372632 INIST</idno><idno type="RBID">Pascal:00-0372632</idno><idno type="wicri:Area/Main/Corpus">012929</idno><idno type="wicri:Area/Main/Repository">012B42</idno></publicationStmt><seriesStmt><idno type="ISSN">0340-6997</idno><title level="j" type="abbreviated">Eur. j. nucl. med.</title><title level="j" type="main">European journal of nuclear medicine</title></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Absorbed dose</term><term>Dose repartition</term><term>Dosimetry</term><term>Human</term><term>Immunoradiotherapy</term><term>Multicenter study</term><term>Non Hodgkin lymphoma</term><term>Phase I trial</term><term>Phase II trial</term><term>Tolerance limit</term><term>Toxicity</term><term>Treatment</term><term>Yttrium</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Lymphome non hodgkinien</term><term>Traitement</term><term>Dosimétrie</term><term>Immunoradiothérapie</term><term>Yttrium</term><term>Homme</term><term>Dose absorbée</term><term>Essai clinique phase I</term><term>Essai clinique phase II</term><term>Etude multicentrique</term><term>Limite tolérance</term><term>Distribution dose</term><term>Toxicité</term></keywords><keywords scheme="Wicri" type="concept" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from <sup>90</sup>Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of <sup>90</sup>Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received <sup>111</sup>In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8) on day 0 followed by a therapeutic dose of <sup>90</sup>Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of <sup>111</sup>In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T<sub>1/2</sub>, blood AUC, plasma T<sub>1/2</sub>. and plasma AUC. It is concluded that <sup>90</sup>Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T<sub>1/2</sub>, reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population.</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0340-6997</s0></fA01><fA02 i1="01"><s0>EJNMD9</s0></fA02><fA03 i2="1"><s0>Eur. j. nucl. med.</s0></fA03><fA05><s2>27</s2></fA05><fA06><s2>7</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Phase I/II <sup>90</sup>Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin's lymphoma</s1></fA08><fA11 i1="01" i2="1"><s1>WISEMAN (G. A.)</s1></fA11><fA11 i1="02" i2="1"><s1>WHITE (C. A.)</s1></fA11><fA11 i1="03" i2="1"><s1>STABIN (M.)</s1></fA11><fA11 i1="04" i2="1"><s1>DUNN (W. L.)</s1></fA11><fA11 i1="05" i2="1"><s1>ERWIN (W.)</s1></fA11><fA11 i1="06" i2="1"><s1>DAHLBOM (M.)</s1></fA11><fA11 i1="07" i2="1"><s1>RAUBITSCHEK (A.)</s1></fA11><fA11 i1="08" i2="1"><s1>KARVELIS (K.)</s1></fA11><fA11 i1="09" i2="1"><s1>SCHULTHEISS (T.)</s1></fA11><fA11 i1="10" i2="1"><s1>WITZIG (T. E.)</s1></fA11><fA11 i1="11" i2="1"><s1>BELANGER (R.)</s1></fA11><fA11 i1="12" i2="1"><s1>SPIES (S.)</s1></fA11><fA11 i1="13" i2="1"><s1>SILVERMAN (D. H. S.)</s1></fA11><fA11 i1="14" i2="1"><s1>BERLFEIN (J. R.)</s1></fA11><fA11 i1="15" i2="1"><s1>DING (E.)</s1></fA11><fA11 i1="16" i2="1"><s1>GRILLO-LOPEZ (A. J.)</s1></fA11><fA14 i1="01"><s1>Department of Radiology, Nuclear Medicine, Mayo Clinic and Mayo Foundation</s1><s2>Rochester, Minn.</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ></fA14><fA14 i1="02"><s1>IDEC Pharmaceuticals Corp.</s1><s2>San Diego, Calif.</s2><s3>USA</s3><sZ>2 aut.</sZ><sZ>14 aut.</sZ><sZ>15 aut.</sZ><sZ>16 aut.</sZ></fA14><fA14 i1="03"><s1>Division of Hematology/Oncology, Department of Medicine, Northwestern University and Robert H. Lurie Comprehensive Cancer Center</s1><s2>Chicago, Ill.</s2><s3>USA</s3><sZ>5 aut.</sZ><sZ>12 aut.</sZ></fA14><fA14 i1="04"><s1>University of California at Los Angeles</s1><s2>Los Angeles, Calif.</s2><s3>USA</s3><sZ>6 aut.</sZ><sZ>13 aut.</sZ></fA14><fA14 i1="05"><s1>City of Hope</s1><s2>Duarte, Calif.</s2><s3>USA</s3><sZ>7 aut.</sZ></fA14><fA14 i1="06"><s1>Henry Ford Hospital</s1><s2>Detroit, Mich.</s2><s3>USA</s3><sZ>8 aut.</sZ></fA14><fA14 i1="07"><s1>Fox Chase Cancer Center</s1><s2>Philadelphia, Pa.</s2><s3>USA</s3><sZ>9 aut.</sZ></fA14><fA14 i1="08"><s1>Department of Internal Medicine Division of Hematology, Mayo Clinic and Mayo Foundation</s1><s2>Rochester, Minn.</s2><s3>USA</s3><sZ>10 aut.</sZ></fA14><fA14 i1="09"><s1>Ryan Belanger Associates</s1><s2>San Diego, Calif.</s2><s3>USA</s3><sZ>11 aut.</sZ></fA14><fA20><s1>766-777</s1></fA20><fA21><s1>2000</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>17140</s2><s5>354000090649090030</s5></fA43><fA44><s0>0000</s0><s1>© 2000 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>21 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>00-0372632</s0></fA47><fA60><s1>P</s1></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>European journal of nuclear medicine</s0></fA64><fA66 i1="01"><s0>DEU</s0></fA66><fC01 i1="01" l="ENG"><s0>Dosimetry studies in patients with non-Hodgkin's lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from <sup>90</sup>Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of <sup>90</sup>Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received <sup>111</sup>In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8) on day 0 followed by a therapeutic dose of <sup>90</sup>Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of <sup>111</sup>In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n=56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2-7.8 Gy), 2.6 Gy to lungs (range 0.72-4.4 Gy), and 0.38 Gy to kidneys (range 0.07-0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8-67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T<sub>1/2</sub>, blood AUC, plasma T<sub>1/2</sub>. and plasma AUC. It is concluded that <sup>90</sup>Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T<sub>1/2</sub>, reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population.</s0></fC01><fC02 i1="01" i2="X"><s0>002B19B</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Lymphome non hodgkinien</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Non Hodgkin lymphoma</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Linfoma no Hodgkin</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Traitement</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Treatment</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Tratamiento</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Dosimétrie</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Dosimetry</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Dosimetría</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Immunoradiothérapie</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Immunoradiotherapy</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Inmunoradioterapia</s0><s5>04</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Yttrium</s0><s2>NC</s2><s5>05</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Yttrium</s0><s2>NC</s2><s5>05</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Ytrio</s0><s2>NC</s2><s5>05</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Homme</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>Human</s0><s5>06</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Hombre</s0><s5>06</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Dose absorbée</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Absorbed dose</s0><s5>07</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Dosis absorbida</s0><s5>07</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Essai clinique phase I</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Phase I trial</s0><s5>08</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Ensayo clínico fase I</s0><s5>08</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Essai clinique phase II</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Phase II trial</s0><s5>09</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Ensayo clínico fase II</s0><s5>09</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Etude multicentrique</s0><s5>10</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Multicenter study</s0><s5>10</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Estudio multicéntrico</s0><s5>10</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>Limite tolérance</s0><s5>11</s5></fC03><fC03 i1="11" i2="X" l="ENG"><s0>Tolerance limit</s0><s5>11</s5></fC03><fC03 i1="11" i2="X" l="SPA"><s0>Límite tolerancia</s0><s5>11</s5></fC03><fC03 i1="12" i2="X" l="FRE"><s0>Distribution dose</s0><s5>12</s5></fC03><fC03 i1="12" i2="X" l="ENG"><s0>Dose repartition</s0><s5>12</s5></fC03><fC03 i1="12" i2="X" l="SPA"><s0>Distribución dosis</s0><s5>12</s5></fC03><fC03 i1="13" i2="X" l="FRE"><s0>Toxicité</s0><s5>13</s5></fC03><fC03 i1="13" i2="X" l="ENG"><s0>Toxicity</s0><s5>13</s5></fC03><fC03 i1="13" i2="X" l="SPA"><s0>Toxicidad</s0><s5>13</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Hémopathie maligne</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Malignant hemopathy</s0><s5>37</s5></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Hemopatía maligna</s0><s5>37</s5></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Lymphoprolifératif syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Lymphoproliferative syndrome</s0><s5>38</s5></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Linfoproliferativo síndrome</s0><s5>38</s5></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Radiothérapie</s0><s5>45</s5></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Radiotherapy</s0><s5>45</s5></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Radioterapia</s0><s5>45</s5></fC07><fN21><s1>255</s1></fN21></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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