A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients
Identifieur interne : 001068 ( Istex/Checkpoint ); précédent : 001067; suivant : 001069A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients
Auteurs : E. Van Cutsem [Belgique] ; C. Verslype [Belgique] ; P. Beale [Australie] ; S. Clarke [Australie] ; R. Bugat [France] ; A. Rakhit [États-Unis] ; S. H. Fettner [États-Unis] ; U. Brennscheidt [Suisse] ; A. Feyereislova [Suisse] ; J.-P Delord [France]Source :
- Annals of Oncology [ 0923-7534 ] ; 2007-11-06.
Abstract
Background: Dysregulation of the epidermal growth factor receptor (HER1/EGFR) has been reported in colorectal cancer (CRC). Erlotinib is a potent inhibitor of HER1/EGFR-mediated signaling. This trial of patients with metastatic CRC (MCRC) examined the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of erlotinib in combination with capecitabine and oxaliplatin (XELOX), a regimen with established efficacy. Patients and methods: Patients previously untreated or treated with one line of 5-fluorouracil and/or irinotecan received escalating oral doses of erlotinib (daily), capecitabine (days 1–14) and i.v. oxaliplatin (day 1 of a 21-day cycle). Results: The first six patients in cohort 1 (erlotinib 100 mg/day, capecitabine 825 mg/m2 twice daily, oxaliplatin 130 mg/m2) had no dose-limiting toxicities (DLTs). In cohort 2 (capecitabine increased to 1000 mg/m2 twice daily), two of six patients had DLTs. When cohort 2 was expanded to 11 patients two further DLTs occurred, exceeding the definition of MTD. Cohort 1 was expanded to 12 patients, and no DLTs occurred. The most common adverse events (AEs) were diarrhea and rash. There was a trend for reduced capecitabine concentrations in the presence of erlotinib. While this was not statistically significant, the possibility of an interaction affecting capecitabine PK cannot be excluded. Antitumor activity was observed in both cohorts (one complete and four partial responses, and stable disease in 11 patients). Conclusion: The MTD for this combination in MCRC is capecitabine 825 mg/m2 twice daily days 1–14, oxaliplatin 130 mg/m2 day 1 and erlotinib 100 mg/day of a 21-day cycle. The combination was well tolerated at the MTD, with no unexpected AEs. The use of this combination in MCRC warrants further investigation.
Url:
DOI: 10.1093/annonc/mdm452
Affiliations:
- Australie, Belgique, France, Suisse, États-Unis
- Midi-Pyrénées, New Jersey, Nouvelle-Galles du Sud, Occitanie (région administrative)
- Sydney, Toulouse
Links toward previous steps (curation, corpus...)
Links to Exploration step
ISTEX:2BBB2A78F3AE8828BCD4594F29A187B89426687CLe document en format XML
<record><TEI wicri:istexFullTextTei="biblStruct"><teiHeader><fileDesc><titleStmt><title>A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients</title><author><name sortKey="Van Cutsem, E" sort="Van Cutsem, E" uniqKey="Van Cutsem E" first="E." last="Van Cutsem">E. Van Cutsem</name></author><author><name sortKey="Verslype, C" sort="Verslype, C" uniqKey="Verslype C" first="C." last="Verslype">C. Verslype</name></author><author><name sortKey="Beale, P" sort="Beale, P" uniqKey="Beale P" first="P." last="Beale">P. Beale</name></author><author><name sortKey="Clarke, S" sort="Clarke, S" uniqKey="Clarke S" first="S." last="Clarke">S. Clarke</name></author><author><name sortKey="Bugat, R" sort="Bugat, R" uniqKey="Bugat R" first="R." last="Bugat">R. Bugat</name></author><author><name sortKey="Rakhit, A" sort="Rakhit, A" uniqKey="Rakhit A" first="A." last="Rakhit">A. Rakhit</name></author><author><name sortKey="Fettner, S H" sort="Fettner, S H" uniqKey="Fettner S" first="S. H." last="Fettner">S. H. Fettner</name></author><author><name sortKey="Brennscheidt, U" sort="Brennscheidt, U" uniqKey="Brennscheidt U" first="U." last="Brennscheidt">U. Brennscheidt</name></author><author><name sortKey="Feyereislova, A" sort="Feyereislova, A" uniqKey="Feyereislova A" first="A." last="Feyereislova">A. Feyereislova</name></author><author><name sortKey="Delord, J P" sort="Delord, J P" uniqKey="Delord J" first="J.-P" last="Delord">J.-P Delord</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:2BBB2A78F3AE8828BCD4594F29A187B89426687C</idno><date when="2008" year="2008">2008</date><idno type="doi">10.1093/annonc/mdm452</idno><idno type="url">https://api.istex.fr/document/2BBB2A78F3AE8828BCD4594F29A187B89426687C/fulltext/pdf</idno><idno type="wicri:Area/Istex/Corpus">000855</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Corpus" wicri:corpus="ISTEX">000855</idno><idno type="wicri:Area/Istex/Curation">000855</idno><idno type="wicri:Area/Istex/Checkpoint">001068</idno><idno type="wicri:explorRef" wicri:stream="Istex" wicri:step="Checkpoint">001068</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a">A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients</title><author><name sortKey="Van Cutsem, E" sort="Van Cutsem, E" uniqKey="Van Cutsem E" first="E." last="Van Cutsem">E. Van Cutsem</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>University Hospital Gasthuisberg, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Belgique</country></affiliation><affiliation><wicri:noCountry code="syntax">???</wicri:noCountry></affiliation><affiliation wicri:level="1"><country wicri:rule="url">Belgique</country></affiliation></author><author><name sortKey="Verslype, C" sort="Verslype, C" uniqKey="Verslype C" first="C." last="Verslype">C. Verslype</name><affiliation wicri:level="1"><country xml:lang="fr">Belgique</country><wicri:regionArea>University Hospital Gasthuisberg, Leuven</wicri:regionArea><wicri:noRegion>Leuven</wicri:noRegion></affiliation></author><author><name sortKey="Beale, P" sort="Beale, P" uniqKey="Beale P" first="P." last="Beale">P. Beale</name><affiliation wicri:level="3"><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney Cancer Centre, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Clarke, S" sort="Clarke, S" uniqKey="Clarke S" first="S." last="Clarke">S. Clarke</name><affiliation wicri:level="3"><country xml:lang="fr">Australie</country><wicri:regionArea>Sydney Cancer Centre, Sydney</wicri:regionArea><placeName><settlement type="city">Sydney</settlement><region type="état">Nouvelle-Galles du Sud</region></placeName></affiliation></author><author><name sortKey="Bugat, R" sort="Bugat, R" uniqKey="Bugat R" first="R." last="Bugat">R. Bugat</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Institut Claudius Regaud, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author><author><name sortKey="Rakhit, A" sort="Rakhit, A" uniqKey="Rakhit A" first="A." last="Rakhit">A. Rakhit</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>F. Hoffmann-La Roche, Nutley, NJ</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Fettner, S H" sort="Fettner, S H" uniqKey="Fettner S" first="S. H." last="Fettner">S. H. Fettner</name><affiliation wicri:level="2"><country xml:lang="fr">États-Unis</country><wicri:regionArea>F. Hoffmann-La Roche, Nutley, NJ</wicri:regionArea><placeName><region type="state">New Jersey</region></placeName></affiliation></author><author><name sortKey="Brennscheidt, U" sort="Brennscheidt, U" uniqKey="Brennscheidt U" first="U." last="Brennscheidt">U. Brennscheidt</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>F. Hoffmann-La Roche Ltd, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation></author><author><name sortKey="Feyereislova, A" sort="Feyereislova, A" uniqKey="Feyereislova A" first="A." last="Feyereislova">A. Feyereislova</name><affiliation wicri:level="1"><country xml:lang="fr">Suisse</country><wicri:regionArea>F. Hoffmann-La Roche Ltd, Basel</wicri:regionArea><wicri:noRegion>Basel</wicri:noRegion></affiliation></author><author><name sortKey="Delord, J P" sort="Delord, J P" uniqKey="Delord J" first="J.-P" last="Delord">J.-P Delord</name><affiliation wicri:level="3"><country xml:lang="fr">France</country><wicri:regionArea>Institut Claudius Regaud, Toulouse</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Midi-Pyrénées</region><settlement type="city">Toulouse</settlement></placeName></affiliation></author></analytic><monogr></monogr><series><title level="j">Annals of Oncology</title><idno type="ISSN">0923-7534</idno><idno type="eISSN">1569-8041</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2007-11-06">2007-11-06</date><biblScope unit="volume">19</biblScope><biblScope unit="issue">2</biblScope><biblScope unit="page" from="332">332</biblScope><biblScope unit="page" to="339">339</biblScope></imprint><idno type="ISSN">0923-7534</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0923-7534</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract">Background: Dysregulation of the epidermal growth factor receptor (HER1/EGFR) has been reported in colorectal cancer (CRC). Erlotinib is a potent inhibitor of HER1/EGFR-mediated signaling. This trial of patients with metastatic CRC (MCRC) examined the safety, maximum tolerated dose (MTD) and pharmacokinetics (PK) of erlotinib in combination with capecitabine and oxaliplatin (XELOX), a regimen with established efficacy. Patients and methods: Patients previously untreated or treated with one line of 5-fluorouracil and/or irinotecan received escalating oral doses of erlotinib (daily), capecitabine (days 1–14) and i.v. oxaliplatin (day 1 of a 21-day cycle). Results: The first six patients in cohort 1 (erlotinib 100 mg/day, capecitabine 825 mg/m2 twice daily, oxaliplatin 130 mg/m2) had no dose-limiting toxicities (DLTs). In cohort 2 (capecitabine increased to 1000 mg/m2 twice daily), two of six patients had DLTs. When cohort 2 was expanded to 11 patients two further DLTs occurred, exceeding the definition of MTD. Cohort 1 was expanded to 12 patients, and no DLTs occurred. The most common adverse events (AEs) were diarrhea and rash. There was a trend for reduced capecitabine concentrations in the presence of erlotinib. While this was not statistically significant, the possibility of an interaction affecting capecitabine PK cannot be excluded. Antitumor activity was observed in both cohorts (one complete and four partial responses, and stable disease in 11 patients). Conclusion: The MTD for this combination in MCRC is capecitabine 825 mg/m2 twice daily days 1–14, oxaliplatin 130 mg/m2 day 1 and erlotinib 100 mg/day of a 21-day cycle. The combination was well tolerated at the MTD, with no unexpected AEs. The use of this combination in MCRC warrants further investigation.</div></front></TEI><affiliations><list><country><li>Australie</li><li>Belgique</li><li>France</li><li>Suisse</li><li>États-Unis</li></country><region><li>Midi-Pyrénées</li><li>New Jersey</li><li>Nouvelle-Galles du Sud</li><li>Occitanie (région administrative)</li></region><settlement><li>Sydney</li><li>Toulouse</li></settlement></list><tree><country name="Belgique"><noRegion><name sortKey="Van Cutsem, E" sort="Van Cutsem, E" uniqKey="Van Cutsem E" first="E." last="Van Cutsem">E. Van Cutsem</name></noRegion><name sortKey="Van Cutsem, E" sort="Van Cutsem, E" uniqKey="Van Cutsem E" first="E." last="Van Cutsem">E. Van Cutsem</name><name sortKey="Van Cutsem, E" sort="Van Cutsem, E" uniqKey="Van Cutsem E" first="E." last="Van Cutsem">E. Van Cutsem</name><name sortKey="Verslype, C" sort="Verslype, C" uniqKey="Verslype C" first="C." last="Verslype">C. Verslype</name></country><country name="Australie"><region name="Nouvelle-Galles du Sud"><name sortKey="Beale, P" sort="Beale, P" uniqKey="Beale P" first="P." last="Beale">P. Beale</name></region><name sortKey="Clarke, S" sort="Clarke, S" uniqKey="Clarke S" first="S." last="Clarke">S. Clarke</name></country><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Bugat, R" sort="Bugat, R" uniqKey="Bugat R" first="R." last="Bugat">R. Bugat</name></region><name sortKey="Delord, J P" sort="Delord, J P" uniqKey="Delord J" first="J.-P" last="Delord">J.-P Delord</name></country><country name="États-Unis"><region name="New Jersey"><name sortKey="Rakhit, A" sort="Rakhit, A" uniqKey="Rakhit A" first="A." last="Rakhit">A. Rakhit</name></region><name sortKey="Fettner, S H" sort="Fettner, S H" uniqKey="Fettner S" first="S. H." last="Fettner">S. H. Fettner</name></country><country name="Suisse"><noRegion><name sortKey="Brennscheidt, U" sort="Brennscheidt, U" uniqKey="Brennscheidt U" first="U." last="Brennscheidt">U. Brennscheidt</name></noRegion><name sortKey="Feyereislova, A" sort="Feyereislova, A" uniqKey="Feyereislova A" first="A." last="Feyereislova">A. Feyereislova</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
EXPLOR_STEP=$WICRI_ROOT/Wicri/Asie/explor/AustralieFrV1/Data/Istex/Checkpoint
HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 001068 | SxmlIndent | more
Ou
HfdSelect -h $EXPLOR_AREA/Data/Istex/Checkpoint/biblio.hfd -nk 001068 | SxmlIndent | more
Pour mettre un lien sur cette page dans le réseau Wicri
{{Explor lien
|wiki= Wicri/Asie
|area= AustralieFrV1
|flux= Istex
|étape= Checkpoint
|type= RBID
|clé= ISTEX:2BBB2A78F3AE8828BCD4594F29A187B89426687C
|texte= A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients
}}
| This area was generated with Dilib version V0.6.33. |  |