Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial
Identifieur interne : 005F99 ( Main/Exploration ); précédent : 005F98; suivant : 006000Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial
Auteurs : Samuel A. Wells [Royaume-Uni] ; Bruce G. Robinson [Royaume-Uni] ; Robert F. Gagel [Royaume-Uni] ; Henning Dralle [Royaume-Uni] ; James A. Fagin [Royaume-Uni] ; Massimo Santoro [Royaume-Uni] ; Eric Baudin [Royaume-Uni] ; Rossella Elisei [Royaume-Uni] ; Barbara Jarzab [Royaume-Uni] ; James R. Vasselli [Royaume-Uni] ; Jessica Read [Royaume-Uni] ; Peter Langmuir [Royaume-Uni] ; Anderson J. Ryan [Royaume-Uni] ; Martin J. Schlumberger [Royaume-Uni]Source :
- Journal of Clinical Oncology [ 0732-183X ] ; 2011.
Abstract
There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC.
Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments.
Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69;
Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).
Url:
DOI: 10.1200/JCO.2011.35.5040
PubMed: 22025146
PubMed Central: 3675689
Affiliations:
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Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Robinson, Bruce G" sort="Robinson, Bruce G" uniqKey="Robinson B" first="Bruce G." last="Robinson">Bruce G. Robinson</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Gagel, Robert F" sort="Gagel, Robert F" uniqKey="Gagel R" first="Robert F." last="Gagel">Robert F. Gagel</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Dralle, Henning" sort="Dralle, Henning" uniqKey="Dralle H" first="Henning" last="Dralle">Henning Dralle</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. 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Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Santoro, Massimo" sort="Santoro, Massimo" uniqKey="Santoro M" first="Massimo" last="Santoro">Massimo Santoro</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Baudin, Eric" sort="Baudin, Eric" uniqKey="Baudin E" first="Eric" last="Baudin">Eric Baudin</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Elisei, Rossella" sort="Elisei, Rossella" uniqKey="Elisei R" first="Rossella" last="Elisei">Rossella Elisei</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Jarzab, Barbara" sort="Jarzab, Barbara" uniqKey="Jarzab B" first="Barbara" last="Jarzab">Barbara Jarzab</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Vasselli, James R" sort="Vasselli, James R" uniqKey="Vasselli J" first="James R." last="Vasselli">James R. Vasselli</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Read, Jessica" sort="Read, Jessica" uniqKey="Read J" first="Jessica" last="Read">Jessica Read</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Langmuir, Peter" sort="Langmuir, Peter" uniqKey="Langmuir P" first="Peter" last="Langmuir">Peter Langmuir</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Ryan, Anderson J" sort="Ryan, Anderson J" uniqKey="Ryan A" first="Anderson J." last="Ryan">Anderson J. Ryan</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Schlumberger, Martin J" sort="Schlumberger, Martin J" uniqKey="Schlumberger M" first="Martin J." last="Schlumberger">Martin J. Schlumberger</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">22025146</idno><idno type="pmc">3675689</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675689</idno><idno type="RBID">PMC:3675689</idno><idno type="doi">10.1200/JCO.2011.35.5040</idno><date when="2011">2011</date><idno type="wicri:Area/Pmc/Corpus">001947</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001947</idno><idno type="wicri:Area/Pmc/Curation">001806</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001806</idno><idno type="wicri:Area/Pmc/Checkpoint">002124</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">002124</idno><idno type="wicri:Area/Ncbi/Merge">000C06</idno><idno type="wicri:Area/Ncbi/Curation">000C06</idno><idno type="wicri:Area/Ncbi/Checkpoint">000C06</idno><idno type="wicri:doubleKey">0732-183X:2011:Wells S:vandetanib:in:patients</idno><idno type="wicri:Area/Main/Merge">006328</idno><idno type="wicri:Area/Main/Curation">005F99</idno><idno type="wicri:Area/Main/Exploration">005F99</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Vandetanib in Patients With Locally Advanced or Metastatic Medullary Thyroid Cancer: A Randomized, Double-Blind Phase III Trial</title><author><name sortKey="Wells, Samuel A" sort="Wells, Samuel A" uniqKey="Wells S" first="Samuel A." last="Wells">Samuel A. Wells</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Robinson, Bruce G" sort="Robinson, Bruce G" uniqKey="Robinson B" first="Bruce G." last="Robinson">Bruce G. Robinson</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Gagel, Robert F" sort="Gagel, Robert F" uniqKey="Gagel R" first="Robert F." last="Gagel">Robert F. Gagel</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Dralle, Henning" sort="Dralle, Henning" uniqKey="Dralle H" first="Henning" last="Dralle">Henning Dralle</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Fagin, James A" sort="Fagin, James A" uniqKey="Fagin J" first="James A." last="Fagin">James A. Fagin</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Santoro, Massimo" sort="Santoro, Massimo" uniqKey="Santoro M" first="Massimo" last="Santoro">Massimo Santoro</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Baudin, Eric" sort="Baudin, Eric" uniqKey="Baudin E" first="Eric" last="Baudin">Eric Baudin</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Elisei, Rossella" sort="Elisei, Rossella" uniqKey="Elisei R" first="Rossella" last="Elisei">Rossella Elisei</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Jarzab, Barbara" sort="Jarzab, Barbara" uniqKey="Jarzab B" first="Barbara" last="Jarzab">Barbara Jarzab</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Vasselli, James R" sort="Vasselli, James R" uniqKey="Vasselli J" first="James R." last="Vasselli">James R. Vasselli</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Read, Jessica" sort="Read, Jessica" uniqKey="Read J" first="Jessica" last="Read">Jessica Read</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Langmuir, Peter" sort="Langmuir, Peter" uniqKey="Langmuir P" first="Peter" last="Langmuir">Peter Langmuir</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Ryan, Anderson J" sort="Ryan, Anderson J" uniqKey="Ryan A" first="Anderson J." last="Ryan">Anderson J. Ryan</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author><author><name sortKey="Schlumberger, Martin J" sort="Schlumberger, Martin J" uniqKey="Schlumberger M" first="Martin J." last="Schlumberger">Martin J. Schlumberger</name><affiliation wicri:level="4"><nlm:aff id="aff1">Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford, United Kingdom.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Royaume-Uni</country><wicri:regionArea>Samuel A. Wells Jr, National Cancer Institute, National Institutes of Health, Bethesda, MD; Bruce G. Robinson, Kolling Institute of Medical Research, University of Sydney, Sydney, Australia; Robert F. Gagel, University of Texas MD Anderson Cancer Center, Houston, TX; Henning Dralle, Martin Luther University Halle-Wittenberg, Halle, Germany; James A. Fagin, Memorial Sloan-Kettering Cancer Center, New York, NY; Massimo Santoro, Universita' di Napoli Federico II, Naples, Italy; Eric Baudin and Martin J. Schlumberger, Institut Gustave Roussy, Villejuif, France; Rossella Elisei, University of Pisa, Pisa, Italy; Barbara Jarzab, Maria Sklodowska-Curie Memorial Cancer Center, Gliwice, Poland; James R. Vasselli and Peter Langmuir, AstraZeneca, Wilmington, DE; Jessica Read, AstraZeneca, Macclesfield; and Anderson J. Ryan, University of Oxford, Oxford</wicri:regionArea><placeName><settlement type="city">Oxford</settlement><region type="country">Angleterre</region><region type="comté" nuts="2">Oxfordshire</region><settlement type="city">Sydney</settlement></placeName><orgName type="university">Université de Sydney</orgName></affiliation></author></analytic><series><title level="j">Journal of Clinical Oncology</title><idno type="ISSN">0732-183X</idno><idno type="eISSN">1527-7755</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Purpose</title><p>There is no effective therapy for patients with advanced medullary thyroid carcinoma (MTC). Vandetanib, a once-daily oral inhibitor of RET kinase, vascular endothelial growth factor receptor, and epidermal growth factor receptor signaling, has previously shown antitumor activity in a phase II study of patients with advanced hereditary MTC.</p></sec><sec><title>Patients and Methods</title><p>Patients with advanced MTC were randomly assigned in a 2:1 ratio to receive vandetanib 300 mg/d or placebo. On objective disease progression, patients could elect to receive open-label vandetanib. The primary end point was progression-free survival (PFS), determined by independent central Response Evaluation Criteria in Solid Tumors (RECIST) assessments.</p></sec><sec><title>Results</title><p>Between December 2006 and November 2007, 331 patients (mean age, 52 years; 90% sporadic; 95% metastatic) were randomly assigned to receive vandetanib (231) or placebo (100). At data cutoff (July 2009; median follow-up, 24 months), 37% of patients had progressed and 15% had died. The study met its primary objective of PFS prolongation with vandetanib versus placebo (hazard ratio [HR], 0.46; 95% CI, 0.31 to 0.69; <italic>P</italic> < .001). Statistically significant advantages for vandetanib were also seen for objective response rate (<italic>P</italic> < .001), disease control rate (<italic>P</italic> = .001), and biochemical response (<italic>P</italic> < .001). Overall survival data were immature at data cutoff (HR, 0.89; 95% CI, 0.48 to 1.65). A final survival analysis will take place when 50% of the patients have died. Common adverse events (any grade) occurred more frequently with vandetanib compared with placebo, including diarrhea (56% <italic>v</italic> 26%), rash (45% <italic>v</italic> 11%), nausea (33% <italic>v</italic> 16%), hypertension (32% <italic>v</italic> 5%), and headache (26% <italic>v</italic> 9%).</p></sec><sec><title>Conclusion</title><p>Vandetanib demonstrated therapeutic efficacy in a phase III trial of patients with advanced MTC (ClinicalTrials.gov NCT00410761).</p></sec></div></front></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Oxfordshire</li></region><settlement><li>Oxford</li><li>Sydney</li></settlement><orgName><li>Université de Sydney</li></orgName></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Wells, Samuel A" sort="Wells, Samuel A" uniqKey="Wells S" first="Samuel A." last="Wells">Samuel A. Wells</name></region><name sortKey="Baudin, Eric" sort="Baudin, Eric" uniqKey="Baudin E" first="Eric" last="Baudin">Eric Baudin</name><name sortKey="Dralle, Henning" sort="Dralle, Henning" uniqKey="Dralle H" first="Henning" last="Dralle">Henning Dralle</name><name sortKey="Elisei, Rossella" sort="Elisei, Rossella" uniqKey="Elisei R" first="Rossella" last="Elisei">Rossella Elisei</name><name sortKey="Fagin, James A" sort="Fagin, James A" uniqKey="Fagin J" first="James A." last="Fagin">James A. Fagin</name><name sortKey="Gagel, Robert F" sort="Gagel, Robert F" uniqKey="Gagel R" first="Robert F." last="Gagel">Robert F. Gagel</name><name sortKey="Jarzab, Barbara" sort="Jarzab, Barbara" uniqKey="Jarzab B" first="Barbara" last="Jarzab">Barbara Jarzab</name><name sortKey="Langmuir, Peter" sort="Langmuir, Peter" uniqKey="Langmuir P" first="Peter" last="Langmuir">Peter Langmuir</name><name sortKey="Read, Jessica" sort="Read, Jessica" uniqKey="Read J" first="Jessica" last="Read">Jessica Read</name><name sortKey="Robinson, Bruce G" sort="Robinson, Bruce G" uniqKey="Robinson B" first="Bruce G." last="Robinson">Bruce G. Robinson</name><name sortKey="Ryan, Anderson J" sort="Ryan, Anderson J" uniqKey="Ryan A" first="Anderson J." last="Ryan">Anderson J. Ryan</name><name sortKey="Santoro, Massimo" sort="Santoro, Massimo" uniqKey="Santoro M" first="Massimo" last="Santoro">Massimo Santoro</name><name sortKey="Schlumberger, Martin J" sort="Schlumberger, Martin J" uniqKey="Schlumberger M" first="Martin J." last="Schlumberger">Martin J. Schlumberger</name><name sortKey="Vasselli, James R" sort="Vasselli, James R" uniqKey="Vasselli J" first="James R." last="Vasselli">James R. Vasselli</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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