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TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG)

Identifieur interne : 003271 ( Main/Exploration ); précédent : 003270; suivant : 003272

TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG)

Auteurs : Trevor Leong [Australie] ; B Mark Smithers ; Michael Michael [Australie] ; Val Gebski [Australie] ; Alex Boussioutas [Australie] ; Danielle Miller [Australie] ; John Simes [Australie] ; John Zalcberg ; Karin Haustermans [Belgique] ; Florian Lordick [Allemagne] ; Christoph Schuhmacher [France] ; Carol Swallow ; Gail Darling ; Rebecca Wong

Source :

RBID : PMC:4507314

Descripteurs français

English descriptors

Abstract

Background

The optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy.

We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the TOPGEAR trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy.

Methods/Design

Eligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given.

The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique.

Discussion

TOPGEAR is an international, intergroup collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. It addresses a globally significant question that will help inform future international standards for clinical practice in resectable gastric cancer.

Trial registration

Australian New Zealand Clinical Trials Registry: ACTRN12609000035224. Registered 30 May 2009


Url:
DOI: 10.1186/s12885-015-1529-x
PubMed: 26194186
PubMed Central: 4507314


Affiliations:


Links toward previous steps (curation, corpus...)


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<keywords scheme="MESH" qualifier="radiation effects" xml:lang="en">
<term>Esophagogastric Junction</term>
</keywords>
<keywords scheme="MESH" qualifier="radiotherapy" xml:lang="en">
<term>Stomach Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="radiothérapie" xml:lang="fr">
<term>Tumeurs de l'estomac</term>
</keywords>
<keywords scheme="MESH" qualifier="surgery" xml:lang="en">
<term>Stomach Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="therapeutic use" xml:lang="en">
<term>Antineoplastic Combined Chemotherapy Protocols</term>
<term>Cisplatin</term>
<term>Epirubicin</term>
<term>Fluorouracil</term>
</keywords>
<keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr">
<term>Tumeurs de l'estomac</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr">
<term>Cisplatine</term>
<term>Fluorouracil</term>
<term>Protocoles de polychimiothérapie antinéoplasique</term>
<term>Épirubicine</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Humans</term>
<term>Perioperative Care</term>
<term>Preoperative Care</term>
<term>Survival Analysis</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Analyse de survie</term>
<term>Chimioradiothérapie adjuvante</term>
<term>Humains</term>
<term>Jonction oesogastrique</term>
<term>Résultat thérapeutique</term>
<term>Soins préopératoires</term>
<term>Soins périopératoires</term>
<term>Tumeurs de l'estomac</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>The optimal management of patients with resectable gastric cancer continues to evolve in Western countries. Following publication of the US Intergroup 0116 and UK Medical Research Council MAGIC trials, there are now two standards of care for adjuvant therapy in resectable gastric cancer, at least in the Western world: postoperative chemoradiotherapy and perioperative epirubicin/cisplatin/fluorouracil (ECF) chemotherapy.</p>
<p>We hypothesize that adding chemoradiation to standard perioperative ECF chemotherapy will achieve further survival gains. We also believe there are advantages to administering chemoradiation in the preoperative rather than postoperative setting. In this article, we describe the
<italic>TOPGEAR</italic>
trial, which is a randomised phase III trial comparing control arm therapy of perioperative ECF chemotherapy with experimental arm therapy of preoperative chemoradiation plus perioperative ECF chemotherapy.</p>
</sec>
<sec>
<title>Methods/Design</title>
<p>Eligible patients with resectable adenocarcinoma of the stomach or gastroesophageal junction will be randomized to receive either perioperative chemotherapy alone (3 preoperative and 3 postoperative cycles of ECF) or perioperative chemotherapy plus preoperative chemoradiation. In the chemoradiation arm, patients receive 2 cycles of ECF plus chemoradiation prior to surgery, and then following surgery 3 further cycles of ECF are given.</p>
<p>The trial is being conducted in two Parts; Part 1 (phase II component) has recruited 120 patients with the aim of assessing feasibility, safety and preliminary efficacy of preoperative chemoradiation. Part 2 (phase III component) will recruit a further 632 patients to provide a total sample size of 752 patients. The primary endpoint of the phase III trial is overall survival. The trial includes quality of life and biological substudies, as well as a health economic evaluation. In addition, the trial incorporates a rigorous quality assurance program that includes real time central review of radiotherapy plans and central review of surgical technique.</p>
</sec>
<sec>
<title>Discussion</title>
<p>
<italic>TOPGEAR</italic>
is an international, intergroup collaboration led by the Australasian Gastro-Intestinal Trials Group (AGITG), in collaboration with the Trans-Tasman Radiation Oncology Group (TROG), European Organisation for Research and Treatment of Cancer (EORTC) and the NCIC Clinical Trials Group. It addresses a globally significant question that will help inform future international standards for clinical practice in resectable gastric cancer.</p>
</sec>
<sec>
<title>Trial registration</title>
<p>Australian New Zealand Clinical Trials Registry:
<ext-link ext-link-type="uri" xlink:href="http://www.anzctr.org.au/">ACTRN12609000035224</ext-link>
. Registered 30 May 2009</p>
</sec>
</div>
</front>
<back>
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<author>
<name sortKey="Macdonald, Js" uniqKey="Macdonald J">JS Macdonald</name>
</author>
<author>
<name sortKey="Smalley, Sr" uniqKey="Smalley S">SR Smalley</name>
</author>
<author>
<name sortKey="Benedetti, J" uniqKey="Benedetti J">J Benedetti</name>
</author>
<author>
<name sortKey="Hundahl, Sa" uniqKey="Hundahl S">SA Hundahl</name>
</author>
<author>
<name sortKey="Estes, Nc" uniqKey="Estes N">NC Estes</name>
</author>
<author>
<name sortKey="Stemmermann, Gn" uniqKey="Stemmermann G">GN Stemmermann</name>
</author>
<author>
<name sortKey="Haller, Dg" uniqKey="Haller D">DG Haller</name>
</author>
<author>
<name sortKey="Ajani, Ja" uniqKey="Ajani J">JA Ajani</name>
</author>
<author>
<name sortKey="Gunderson, Ll" uniqKey="Gunderson L">LL Gunderson</name>
</author>
<author>
<name sortKey="Jessup, Jm" uniqKey="Jessup J">JM Jessup</name>
</author>
</analytic>
</biblStruct>
<biblStruct>
<analytic>
<author>
<name sortKey="Cunningham, D" uniqKey="Cunningham D">D Cunningham</name>
</author>
<author>
<name sortKey="Allum, Wh" uniqKey="Allum W">WH Allum</name>
</author>
<author>
<name sortKey="Stenning, Sp" uniqKey="Stenning S">SP Stenning</name>
</author>
<author>
<name sortKey="Thompson, Jn" uniqKey="Thompson J">JN Thompson</name>
</author>
<author>
<name sortKey="Van De Velde, Cj" uniqKey="Van De Velde C">CJ Van de Velde</name>
</author>
<author>
<name sortKey="Nicolson, M" uniqKey="Nicolson M">M Nicolson</name>
</author>
<author>
<name sortKey="Scarffe, Jh" uniqKey="Scarffe J">JH Scarffe</name>
</author>
<author>
<name sortKey="Lofts, Fj" uniqKey="Lofts F">FJ Lofts</name>
</author>
<author>
<name sortKey="Falk, Sj" uniqKey="Falk S">SJ Falk</name>
</author>
<author>
<name sortKey="Iveson, Tj" uniqKey="Iveson T">TJ Iveson</name>
</author>
</analytic>
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<name sortKey="Ajani, Ja" uniqKey="Ajani J">JA Ajani</name>
</author>
<author>
<name sortKey="Mansfield, Pf" uniqKey="Mansfield P">PF Mansfield</name>
</author>
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</author>
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</author>
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<name sortKey="Cohen, Ds" uniqKey="Cohen D">DS Cohen</name>
</author>
</analytic>
</biblStruct>
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<analytic>
<author>
<name sortKey="Ajani, Ja" uniqKey="Ajani J">JA Ajani</name>
</author>
<author>
<name sortKey="Winter, K" uniqKey="Winter K">K Winter</name>
</author>
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<name sortKey="Okawara, Gs" uniqKey="Okawara G">GS Okawara</name>
</author>
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<name sortKey="Pisters, Pw" uniqKey="Pisters P">PW Pisters</name>
</author>
<author>
<name sortKey="Crane, Ch" uniqKey="Crane C">CH Crane</name>
</author>
<author>
<name sortKey="Greskovich, Jf" uniqKey="Greskovich J">JF Greskovich</name>
</author>
<author>
<name sortKey="Anne, Pr" uniqKey="Anne P">PR Anne</name>
</author>
<author>
<name sortKey="Bradley, Jd" uniqKey="Bradley J">JD Bradley</name>
</author>
<author>
<name sortKey="Willett, C" uniqKey="Willett C">C Willett</name>
</author>
</analytic>
</biblStruct>
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<author>
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</author>
<author>
<name sortKey="Gunven, P" uniqKey="Gunven P">P Gunven</name>
</author>
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<name sortKey="Okabayashi, K" uniqKey="Okabayashi K">K Okabayashi</name>
</author>
<author>
<name sortKey="Sasako, M" uniqKey="Sasako M">M Sasako</name>
</author>
<author>
<name sortKey="Kinoshita, T" uniqKey="Kinoshita T">T Kinoshita</name>
</author>
</analytic>
</biblStruct>
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<analytic>
<author>
<name sortKey="Fiorica, F" uniqKey="Fiorica F">F Fiorica</name>
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</author>
<author>
<name sortKey="Enea, M" uniqKey="Enea M">M Enea</name>
</author>
<author>
<name sortKey="Licata, A" uniqKey="Licata A">A Licata</name>
</author>
<author>
<name sortKey="Cabibbo, G" uniqKey="Cabibbo G">G Cabibbo</name>
</author>
<author>
<name sortKey="Carau, B" uniqKey="Carau B">B Carau</name>
</author>
<author>
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</author>
<author>
<name sortKey="Ursino, S" uniqKey="Ursino S">S Ursino</name>
</author>
<author>
<name sortKey="Camma, C" uniqKey="Camma C">C Camma</name>
</author>
</analytic>
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<analytic>
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<name sortKey="Valentini, V" uniqKey="Valentini V">V Valentini</name>
</author>
<author>
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</author>
<author>
<name sortKey="Minsky, Bd" uniqKey="Minsky B">BD Minsky</name>
</author>
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<author>
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<author>
<name sortKey="Nicolotti, N" uniqKey="Nicolotti N">N Nicolotti</name>
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</author>
</analytic>
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</TEI>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>Australie</li>
<li>Belgique</li>
<li>France</li>
</country>
<region>
<li>District de Leipzig</li>
<li>Nouvelle-Galles du Sud</li>
<li>Saxe (Land)</li>
<li>Île-de-France</li>
</region>
<settlement>
<li>Leipzig</li>
<li>Paris</li>
<li>Sydney</li>
</settlement>
<orgName>
<li>Université de Sydney</li>
</orgName>
</list>
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<name sortKey="Darling, Gail" sort="Darling, Gail" uniqKey="Darling G" first="Gail" last="Darling">Gail Darling</name>
<name sortKey="Smithers, B Mark" sort="Smithers, B Mark" uniqKey="Smithers B" first="B Mark" last="Smithers">B Mark Smithers</name>
<name sortKey="Swallow, Carol" sort="Swallow, Carol" uniqKey="Swallow C" first="Carol" last="Swallow">Carol Swallow</name>
<name sortKey="Wong, Rebecca" sort="Wong, Rebecca" uniqKey="Wong R" first="Rebecca" last="Wong">Rebecca Wong</name>
<name sortKey="Zalcberg, John" sort="Zalcberg, John" uniqKey="Zalcberg J" first="John" last="Zalcberg">John Zalcberg</name>
</noCountry>
<country name="Australie">
<noRegion>
<name sortKey="Leong, Trevor" sort="Leong, Trevor" uniqKey="Leong T" first="Trevor" last="Leong">Trevor Leong</name>
</noRegion>
<name sortKey="Boussioutas, Alex" sort="Boussioutas, Alex" uniqKey="Boussioutas A" first="Alex" last="Boussioutas">Alex Boussioutas</name>
<name sortKey="Gebski, Val" sort="Gebski, Val" uniqKey="Gebski V" first="Val" last="Gebski">Val Gebski</name>
<name sortKey="Michael, Michael" sort="Michael, Michael" uniqKey="Michael M" first="Michael" last="Michael">Michael Michael</name>
<name sortKey="Miller, Danielle" sort="Miller, Danielle" uniqKey="Miller D" first="Danielle" last="Miller">Danielle Miller</name>
<name sortKey="Simes, John" sort="Simes, John" uniqKey="Simes J" first="John" last="Simes">John Simes</name>
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<country name="Belgique">
<noRegion>
<name sortKey="Haustermans, Karin" sort="Haustermans, Karin" uniqKey="Haustermans K" first="Karin" last="Haustermans">Karin Haustermans</name>
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</country>
<country name="Allemagne">
<region name="Saxe (Land)">
<name sortKey="Lordick, Florian" sort="Lordick, Florian" uniqKey="Lordick F" first="Florian" last="Lordick">Florian Lordick</name>
</region>
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<country name="France">
<region name="Île-de-France">
<name sortKey="Schuhmacher, Christoph" sort="Schuhmacher, Christoph" uniqKey="Schuhmacher C" first="Christoph" last="Schuhmacher">Christoph Schuhmacher</name>
</region>
</country>
</tree>
</affiliations>
</record>

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