AustralieFrV1, Main, Curation, bibRecord, 008702

A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients

Identifieur interne : 008702 ( Main/Curation ); précédent : 008701; suivant : 008703

A 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.

RBID : ISTEX:2BBB2A78F3AE8828BCD4594F29A187B89426687C

Descripteurs français

Pascal (Inist)
- Anticancéreux, Cancer colorectal, Capécitabine, Dose croissante, Erlotinib, Homme, Métastase, Oxaliplatine, Protocole XELOX, Protocole thérapeutique, Stade avancé.
Wicri :
- topic : Homme.

English descriptors

KwdEn :
- Advanced stage, Antineoplastic agent, Capecitabine, Colorectal cancer, Erlotinib, Human, Increasing dose, Metastasis, Oxaliplatin, Therapeutic protocol.

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:

https://api.istex.fr/document/2BBB2A78F3AE8828BCD4594F29A187B89426687C/fulltext/pdf

DOI: 10.1093/annonc/mdm452

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E. Van Cutsem

<affiliation><wicri:noCountry code="syntax">???</wicri:noCountry>
</affiliation>

<affiliation wicri:level="1"><country wicri:rule="url">Belgique</country>
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Le document en format XML

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<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>
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<affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Sydney Cancer Centre</s1>
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<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
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<placeName><settlement type="city">Sydney</settlement>
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<author><name sortKey="Clarke, S" sort="Clarke, S" uniqKey="Clarke S" first="S." last="Clarke">S. Clarke</name>
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<s2>Sydney</s2>
<s3>AUS</s3>
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<country>Australie</country>
<placeName><settlement type="city">Sydney</settlement>
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<author><name sortKey="Bugat, R" sort="Bugat, R" uniqKey="Bugat R" first="R." last="Bugat">R. Bugat</name>
<affiliation wicri:level="3"><inist:fA14 i1="03"><s1>Institut Claudius Regaud</s1>
<s2>Toulouse</s2>
<s3>FRA</s3>
<sZ>5 aut.</sZ>
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<settlement type="city">Toulouse</settlement>
</placeName>
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<author><name sortKey="Rakhit, A" sort="Rakhit, A" uniqKey="Rakhit A" first="A." last="Rakhit">A. Rakhit</name>
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<author><name sortKey="Fettner, S H" sort="Fettner, S H" uniqKey="Fettner S" first="S. H." last="Fettner">S. H. Fettner</name>
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<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>F Hoffmann-La Roche Ltd</s1>
<s2>Basel</s2>
<s3>CHE</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
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<country>Suisse</country>
<wicri:noRegion>F Hoffmann-La Roche Ltd</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"><inist:fA14 i1="05"><s1>F Hoffmann-La Roche Ltd</s1>
<s2>Basel</s2>
<s3>CHE</s3>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>Suisse</country>
<wicri:noRegion>F Hoffmann-La Roche Ltd</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"><inist:fA14 i1="03"><s1>Institut Claudius Regaud</s1>
<s2>Toulouse</s2>
<s3>FRA</s3>
<sZ>5 aut.</sZ>
<sZ>10 aut.</sZ>
</inist:fA14>
<country>France</country>
<placeName><region type="region">Occitanie (région administrative)</region>
<region type="old region">Midi-Pyrénées</region>
<settlement type="city">Toulouse</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Annals of oncology</title>
<title level="j" type="abbreviated">Ann. oncol.</title>
<idno type="ISSN">0923-7534</idno>
<imprint><date when="2008">2008</date>
</imprint>
</series>
</biblStruct>
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<seriesStmt><title level="j" type="main">Annals of oncology</title>
<title level="j" type="abbreviated">Ann. oncol.</title>
<idno type="ISSN">0923-7534</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Advanced stage</term>
<term>Antineoplastic agent</term>
<term>Capecitabine</term>
<term>Colorectal cancer</term>
<term>Erlotinib</term>
<term>Human</term>
<term>Increasing dose</term>
<term>Metastasis</term>
<term>Oxaliplatin</term>
<term>Therapeutic protocol</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Dose croissante</term>
<term>Erlotinib</term>
<term>Capécitabine</term>
<term>Oxaliplatine</term>
<term>Stade avancé</term>
<term>Métastase</term>
<term>Cancer colorectal</term>
<term>Homme</term>
<term>Protocole thérapeutique</term>
<term>Anticancéreux</term>
<term>Protocole XELOX</term>
</keywords>
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<front><div type="abstract" xml:lang="en">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/m<sup>2</sup>
 twice daily, oxaliplatin 130 mg/m<sup>2</sup>
) had no dose-limiting toxicities (DLTs). In cohort 2 (capecitabine increased to 1000 mg/m<sup>2</sup>
 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/m<sup>2</sup>
 twice daily days 1-14, oxaliplatin 130 mg/m<sup>2</sup>
 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>
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<author><name sortKey="Beale, P" sort="Beale, P" uniqKey="Beale P" first="P." last="Beale">P. Beale</name>
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<author><name sortKey="Brennscheidt, U" sort="Brennscheidt, U" uniqKey="Brennscheidt U" first="U." last="Brennscheidt">U. Brennscheidt</name>
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<wicri:regionArea>University Hospital Gasthuisberg, Leuven</wicri:regionArea>
<wicri:noRegion>Leuven</wicri:noRegion>
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<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>
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<placeName><settlement type="city">Sydney</settlement>
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<wicri:noRegion>Basel</wicri:noRegion>
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<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>
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<placeName><region type="region">Occitanie (région administrative)</region>
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<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>
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A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients

A phase Ib dose-escalation study of erlotinib, capecitabine and oxaliplatin in metastatic colorectal cancer patients

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